STAT1200

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STUDY PROTOCOL

The Efficacy of the Statinzyme Study Product

on Muscle Aches and Discomfort
An open-label, adaptive-design, remote study
Protocol code:

STAT1200

Date of protocol:

December 29, 2014

IND#:

Not Applicable

Clinical phase:

II

Investigational product:

Statinzyme Study Product

Sponsor:
Prescription Vitamins, LLC

CRO:

Medicus Research, LLC

28720 Roadside Drive, Suite 310
Agoura Hills, CA 91301

The information in this document is confidential and provided to you as investigator or consultant
for review by you, your staff, and applicable institutional ethics committees. By accepting this
document you agree that the information contained herein will not be disclosed to others without
authorization of Medicus Research or Prescription Vitamins, LLC.

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS

ITEM
>
<
~
AE
AR
ALC
BP
BPM
C
CFR
CS
CRF
DBP
E.G.
FOCBP
G
GCP
GMP
Ht
HIPAA
HIV
HR
HupA
i.e.
IB
IBS
ICD
ICH
ID
IEC
IRB/EC
IUD
MedDRA
Mg
Min
mmHg
n

DEFINITION
GREATER THAN
LESS THAN
APPROXIMATELY
ADVERSE EVENT
ADVERSE REACTION
ACETYL-L-CARNITINE HCL
BLOOD PRESSURE
BEATS PER MINUTE
CENTIGRADE (CELSIUS)
CODE OF FEDERAL REGULATIONS
CLINICALLY SIGNIFICANT
CASE REPORT FORM
DIASTOLIC BLOOD PRESSURE
EXEMPLI GRATIA (FOR EXAMPLE)
FEMALES OF CHILD BEARING POTENTIAL
GRAM (S)
GOOD CLINICAL PRACTICES
GOOD MANUFACTURING PRACTICES
HEIGHT
HEALTH INSURANCE PORTABILITY AND ACCOUNTABILITYACT
HUMAN IMMUNODEFICIENCY VIRUS
HEART RATE
HUPERZINE A
ID EST (THAT IS)
INVESTIGATOR BROCHURE
IRRITABLE BOWEL SYNDROME
INFORMED CONSENT DOCUMENT
INTERNATIONAL CONFERENCE ON HARMONIZATION
IDENTIFICATION NUMBER
INDEPENDENT ETHICS COMMITTEE
INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE
INTRA UTERINE DEVICE
MEDICAL DICTIONARY FOR REGULATORY ACTIVITIES
MILLIGRAM (S)
MINUTE(S)/MINIMUM
MILLIMETER HYDRARGYRUM = MERCURY (MEASUREMENT OF BLOOD
PRESSURE)
NUMBER /FREQUENCY
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NCI(C)
NIH
NSAIDs
PE
PI
POMS
QD
RR
SAE
SAR
SBP
SOP
SUSAR
T
UNK
VIN
VS
WHO
Wt
X

NATIONAL CANCER INSTITUTE (CRITERIA)

NATIONAL INSTITUTESOF HEALTH
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
PHYSICAL EXAM
PRINCIPAL INVESTIGATOR
PROFILE OF MOODS STATE
DAILY
RESPIRATORY RATE
SERIOUS ADVERSE EVENT
SERIOUS ADVERSE REACTION
SYSTOLIC BLOOD PRESSURE
STANDARD OPERATING PROCEDURE
SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTION
TIME
UNKNOWN
VINPOCETINE
VITAL SIGNS
WORLD HEALTH ORGANIZATION
WEIGHT
TIMES

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Table of Contents
STUDY............................................................................................................................................1
1. PROTOCOL SUMMARY.......................................................................................................7
2. INTRODUCTION.................................................................................................................10
3. NON-REQUIREMENT OF IND..........................................................................................11
4. DESCRIPTION AND RATIONALE...................................................................................12
4.1
4.2

STUDY PURPOSE..................................................................................................................12
GUIDELINES FOR THE DEVELOPMENT OF THE STUDY PROTOCOL........................12

5. STUDY OBJECTIVES AND ENDPOINTS........................................................................13

5.1

PRIMARY OBJECTIVE.........................................................................................................13
5.1.1 PRIMARY ENDPOINTS:................................................................................................................13

5.2

SECONDARY OBJECTIVE...................................................................................................13
5.2.1 SECONDARY ENDPOINTS:.........................................................................................................13

6. SAMPLE SIZE.......................................................................................................................14
7. STUDY DESIGN....................................................................................................................15
7.1
7.2

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, REMOTE, ADAPTIVEDESIGN STUDY....................................................................................................................15

STUDY CENTERS.................................................................................................................15

8. INCLUSION / EXCLUSION CRITERIA...........................................................................16

8.1
8.2

INCLUSION CRITERIA.........................................................................................................16
EXCLUSION CRITERIA........................................................................................................16

9. SAFETY AND TOLERABILITY.........................................................................................17

9.1

SAFETY AND TOLERABILITY WILL BE ASSESSED BY REVIEWING ADVERSE

EVENT REPORTS..................................................................................................................17
9.2
ADVERSE EVENTS...............................................................................................................17
10......................................................................................... VISITS AND SCHEDULE

18
10.1

STUDY START AND TREATMENT......................................................................................18

10.1.1 V1 ONLINE SCREEN................................................................................................................18
10.1.2 V1.5 PHONE SCREEN..............................................................................................................18
10.1.3 RUN-IN PERIOD..........................................................................................................................18
10.1.4 ENROLMENT/SHIPMENT/STUDY PRODUCT CONSUMPTION:.........................................18
10.1.5 V2 (WEEK 0)..............................................................................................................................19
10.1.6 V3 (WEEK 4)..............................................................................................................................19
10.1.7 V4 (WEEK 8) END OF STUDY.............................................................................................20

11.................................................................. INVESTIGATIONAL STUDY PRODUCT

21
11.1

PRODUCT IDENTITY / DOSING..........................................................................................21

11.1.1 STATINZYME STUDY PRODUCT.............................................................................................21

11.2
11.3
11.4
11.5
11.6
11.7

STORAGE...............................................................................................................................22
PACKAGING AND DISPENSING.........................................................................................22
LABELLING...........................................................................................................................23
ACCOUNTABILITY..............................................................................................................24
DISPENSING..........................................................................................................................24
CONCOMITANT MEDICATION...........................................................................................25
11.7.1 PROHIBITED MEDICATIONS AND INTERVENTIONS..........................................................25

12.................................................... DATA ANALYSIS AND STATISTICAL METHODS

26
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12.1 ENROLLMENT......................................................................................................................26
12.2 DATA MANAGEMENT..........................................................................................................26
12.3 EXAMINATION OF DATA....................................................................................................26
12.4 DATA LOCK AND UNBLINDING........................................................................................26
12.5 DESCRIPTIVE SUMMARIZATION......................................................................................27
12.6 COMPLIANCE CALCULATION...........................................................................................27
12.7 STATISTICAL HYPOTHESES...............................................................................................27
12.8 STATISTICAL ANALYSIS.....................................................................................................27
12.9 CONTROL OF INFERENCE ERRORS..................................................................................28
12.10 ANALYTICAL POPULATIONS.............................................................................................28
12.11 FINAL REPORT AND FINAL RESEARCH CLOSEOUT BINDER......................................29
13................................................................................................. ADMINISTRATION

30
13.1 DOCUMENTATION, RECORD ACCESS AND ARCHIVING..............................................30
13.2 DATA PROTECTION..............................................................................................................30
13.3 ESSENTIAL DOCUMENTS...................................................................................................30
13.4 CASE REPORT FORMS (CRFS), DIARIES..........................................................................30
13.5 ARCHIVING...........................................................................................................................31
14......................................................................... ADMINISTRATIVE PROCEDURES

32
14.1 AMENDMENTS TO THE PROTOCOL.................................................................................32
14.2 DISCLOSURE OF ALL INFORMATION AND RESULTS...................................................32
14.3 PUBLICATION.......................................................................................................................32
15............................................................................ PROTOCOL IMPLEMENTATION

33
15.1 PROTOCOL MODIFICATIONS.............................................................................................33
15.2 PROTOCOL DEVIATIONS....................................................................................................33
15.3 QUALITY ASSURANCE AND QUALITY CONTROL........................................................33
15.4 MONITORING........................................................................................................................33
16....................................................................................................... FINAL REPORT

34
17........................................................... ADVERSE EVENTS AND SAFETY ASPECTS
35
17.1 DEFINITION OF ADVERSE EVENT....................................................................................35
17.2 DEFINITION OF SERIOUS ADVERSE EVENT...................................................................35
17.3 DETERMINATION OF THE LIKELIHOOD OF CAUSALITY............................................36
17.4 MONITORING OF ADVERSE EVENTS...............................................................................37
17.5 REPORTING REQUIREMENTS............................................................................................37
18........................................................................ PREMATURE DISCONTINUATION

39
19.................................................................................. REGULATORY AND ETHICS
40
19.1
19.2
19.3
19.4

ETHICAL CONDUCT OF THE STUDY................................................................................40

INSTITUTIONAL REVIEW BOARD (IRB)..........................................................................40
SUBJECT INFORMED CONSENT........................................................................................40
REQUIREMENTS BY THE INVESTIGATOR(S) AND THE STUDY CENTER..................41

APPENDIX 1: STANFORD EXERCISE BEHAVIOR SCALE................................................................43

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APPENDIX 2: VAS PAIN AND SORENESS SCALE..............................................................................44

APPENDIX 3: MOBILE APPLICATIONS...............................................................................................45
APPENDIX 4: POMS...............................................................................................................................47
APPENDIX 4: PHONE SCREEN.............................................................................................................49

TABLE 1: STUDY FLOW CHART............................................................................................................9

TABLE 2: ADVERSE EVENTS...............................................................................................................18

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1. PROTOCOL SUMMARY
PROTOCOL CODE
PROTOCOL TITLE
STUDY DESIGN
CLINICAL PHASE
NUMBER OF
CENTERS

STAT1200
The Efficacy of the Statinzyme Study Product on Muscle Aches and
Discomfort
An open-label, adaptive-design, remote study
II
I
The study duration is approximately 9 weeks for each subject.

STUDY
PERFORMANCE
MAIN STUDY

INCLUSION
CRITERIA

EXCLUSION
CRITERIA

V1 Week (-1) Online Screen

V1.5 Phone Screen
V2 Week 0
V3 Week 4
V4 Week 8 End of Study

RESCUE
MEDICATION
INVESTIGATIONA
L PRODUCTS
PRIMARY
OBJECTIVES
PRIMARY
ENDPOINTS

Healthy subjects 18-65 years of age

Subjects with chronic muscle aches and discomfort
Subjects currently on Statins
Judged by the Investigator to be in general good health
Pregnant and/or lactating women
Subjects with any liver condition including hepatitis, fatty liver, liver
disease
Use of any immunosuppressive drugs in the last 12 months (including
steroids or biologics)
Subjects with any history of immune system disorders or auto-immune
disorders
Subject has a known allergy to the test materials active or inactive
ingredients

None

Statinzyme Study Product

The primary objective is to assess the efficacy of the Statinzyme Study

Product on providing relief of muscle aches and discomfort

Change in VAS Pain and Soreness Scale

Change in Stanford Exercise Behavior Scale
Change in self-reported questionnaires
neuropathy)

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(including

peripheral

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SECONDARY
OBJECTIVE
SECONDARY
ENDPOINTS
SAMPLE SIZE

The secondary objective is to assess the efficacy of the Statinzyme Study

Product on improving memory and mood

Change in POMS questionnaire

The study will enroll 25 subjects

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TABLE 1: STUDY FLOW CHART

V1

V1.5

Protocol Activity

Online
Screening
Week (-1)

Phone
Screening/

Virtual Informed Consent Process

Virtual Inclusion / Exclusion

Medical History

V2

V3

V4

Week 0

Week 4

Week 8
End of
Study

Review Concomitant Therapies

Adverse Event Review

Compliance Phone Call

Run-In
Period

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2. INTRODUCTION

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3. NON-REQUIREMENT OF IND
The current study does not require an IND (Investigational New Drug) application as the test
product is classified as a dietary supplement under the 1994 DSHEA (Dietary Supplement Health
Education Act) regulation.
The FDA issued draft guidance in 2010 Guidance for Industry: Investigational New Drug
Applications (INDs) Determining whether human research studies can be conducted without an
IND.
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
UCM229175.pdf). In that document, Section VI.C (p9) states that whether an IND is needed for
a clinical investigation evaluating a dietary supplement is determined by the intent of the clinical
investigation. If the clinical investigation is intended only to evaluate the dietary supplements
effect on the structure or function of the body, an IND is not required.
Therefore, in concordance with these regulations and guidance, this current study has been
specifically designed to evaluate only the effect of the test product on the structure and/or
function of the body. Specifically we have made a conscious effort not to include diseased
subjects and not to evaluate disease endpoints.
According to 21 CFR 50.25 (c), all applicable clinical trials initiated on or before March 7, 2012
must include the following statements:
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required
by U.S. Law. This Web site will not include information that can identify you. At most, the Web
site will include a summary of the results. You can search this Web site at any time.
This clinical trial does NOT meet the criteria of an applicable clinical trial as it does not involve
a drug, biologic, or device and because it is not conducted under an IND or IDE.

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4. DESCRIPTION AND RATIONALE

4.1

STUDY PURPOSE

The purpose of this study is to determine the effects of the Statinzyme Study Product on
providing relief of muscle aches and discomfort, and improving memory and mood.
4.2

GUIDELINES FOR THE DEVELOPMENT OF THE STUDY PROTOCOL

Guidelines and laws that have been observed in this protocol:

Declaration of Helsinki, version 1996
Note for guidance on good clinical practice (ICH-GCP)

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5. STUDY OBJECTIVES AND ENDPOINTS

5.1

PRIMARY OBJECTIVE

The primary objective is to assess the efficacy of the Statinzyme Study Product on providing
relief of muscle aches and discomfort
5.1.1

5.2

Primary Endpoints:

Change in VAS Pain and Soreness Scale

Change in Stanford Exercise Behavior Scale

Change in self-reported questionnaire (including peripheral neuropathy)

SECONDARY OBJECTIVE

The secondary objective is to assess the efficacy of the Statinzyme Study Product on improving
memory and mood
5.2.1

Secondary Endpoints:

Change in POMS questionnaire

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6. SAMPLE SIZE
The study will enroll 25 subjects. There is no prior human data on this particular study and
endpoints to perform a power calculation.

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7. STUDY DESIGN
7.1

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, REMOTE, ADAPTIVEDESIGN STUDY

7.2

STUDY CENTERS

This study will be conducted at 1 virtual study center.

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8. INCLUSION / EXCLUSION CRITERIA

8.1

INCLUSION CRITERIA

8.2

Healthy subjects 18-65 years of age

Subjects with chronic muscle aches and discomfort
Subjects currently on Statins
Judged by the Investigator to be in general good health

EXCLUSION CRITERIA

Pregnant and/or lactating women

Subjects with any liver condition including hepatitis, fatty liver, liver disease
Use of any immunosuppressive drugs in the last 12 months (including steroids or
biologics)
Subjects with any history of immune system disorders or auto-immune disorders
Subject has a known allergy to the test materials active or inactive ingredients

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9. SAFETY AND TOLERABILITY

9.1

SAFETY AND TOLERABILITY WILL BE ASSESSED BY REVIEWING ADVERSE EVENT

REPORTS.

9.2

ADVERSE EVENTS

Frequency and intensity of AEs and serious AEs will be recorded in detail, based on the
subjects interviews during each visit.
To obtain comparable documentation on AEs, the investigator will ask the subject the following
open, standardized, questions during each visit.

TABLE 2: ADVERSE EVENTS

Have you consulted any type of doctor (MD, Dentist, Podiatrist, Chiropractor, etc), gone to the
emergency room, or experienced any changes in your health since the last visit? Yes1No2
If yes, please fill out the ADVERSE EVENT HISTORY LOG
Have you started taking any new prescriptions or over-the-counter medications, herbs or
supplements since your last visit? Yes1No2
If yes, please fill out the CONCOMITANT MEDICATION LOG. Medications which are
taken as a result of a new sign, symptom, or worsening of pre-existing medical conditions
should also be captured on the ADVERSE EVENT HISTORY LOG
Have you adjusted the dose, or stopped taking any of the medications, herbs, or supplements you
were already taking? Yes1No2
If yes, please fill out the CONCOMITANT MEDICATION LOG

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10. VISITS AND SCHEDULE

10.1 STUDY START AND TREATMENT
The study duration for each individual will be approximately 9 weeks. There will be a total of 5
virtual visits for this study. Subjects may receive a compliance call prior to their next visit.
10.1.1 V1 Online Screen
Virtual Inclusion / Exclusion Criteria: Subjects will complete an online screening to
determine study eligibility.
Virtual Informed Consent Process: Subjects who were determined as eligible in the
study will view an online document explaining the nature of the study, and the potential
risks and/or benefits associated with participating in the study. All potential study subjects
will review and electronically agree to the Consent Information Document.
10.1.2 V1.5 Phone Screen
Subjects will be interviewed over the phone by one of the clinic staff to confirm the
following:

Virtual Inclusion / Exclusion Criteria: Subjects will be interviewed over the

phone by one of the clinic staff to confirm the inclusion and exclusion criteria.

Virtual Medical History: Subject will be interviewed regarding prior medical

history, date of onset of smoking history and status of health, including a verbal
review of systems.

Virtual Interview of Prior and Concomitant Medications: Subjects will be

interviewed regarding their complete history of all medications taken. Subjects will
be instructed regarding permitted and prohibited concomitant medications.

Subjects will be sent an email containing the code to download the mobile applications.
10.1.3 Run-In Period
Subjects will be required to undergo a one-week run-in period during which they will
record a minimum level of aches and discomfort as well as complete scales and
questionnaires for baseline measurements and to demonstrate compliance and technical
competence.
10.1.4 Enrolment/Shipment/Study Product Consumption:
Subjects who meet all of the inclusion criteria and none of the exclusion criteria will be
virtually enrolled into the study. Subjects will receive study products. Subjects will begin
study product consumption on Virtual V2 (Week 0).
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10.1.5 V2 (Week 0)
Study Product Consumption: Subjects will begin taking two capsules twice a day for
four weeks.
Compliance call including Intercurrent Medical History and Concomitant Medication
History: Subjects will be interviewed over the phone by the clinic staff to determine
whether there have been any changes in their medical history, or whether they have started
taking any new medications.
Adverse Event Review: Subjects will be asked an open and standardized question to
obtain comparable documentation on Adverse Event(s).
Mobile Applications: Subjects will begin using the mobile applications.
o eCompliance: Subjects will document daily consumption of study product
Subjects will video record themselves when consuming study
product.
o eDiary: Subjects will record daily symptoms
VAS Pain and Soreness Scale
Stanford Exercise Behavior Scale
Self-reported questionnaire
o POMS Questionnaire: Subjects will complete the questionnaire at this
visit.
10.1.6 V3 (Week 4)
Study Product Consumption: Subjects will now take two capsules once a day for the
remainder of the study.
Compliance call including Intercurrent Medical History and Concomitant Medication
History: Subjects will be interviewed over the phone by the clinic staff to determine
whether there have been any changes in their medical history, or whether they have started
taking any new medications.
Adverse Event Review: Subjects will be asked an open and standardized question to
obtain comparable documentation on Adverse Event(s).
Mobile Applications: Subjects will continue to use the mobile applications.
o eCompliance: Subjects will document daily consumption of study product
Subjects will video record themselves when consuming study
product.
o eDiary: Subjects will record daily symptoms
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VAS Pain and Soreness Scale

Stanford Exercise Behavior Scale
Self-reported questionnaire

o POMS Questionnaire: Subjects will complete the questionnaire at this

visit.
10.1.7 V4 (Week 8) End of Study
Compliance call including Intercurrent Medical History and Concomitant Medication
History: Subjects will be interviewed over the phone by the clinic staff to determine
whether there have been any changes in their medical history, or whether they have started
taking any new medications.
Adverse Event Review: Subjects will be asked an open and standardized question to
obtain comparable documentation on Adverse Event(s).
Mobile Applications: Subjects will continue to use the mobile applications.
o eDiary: Subjects will record their final symptoms
VAS Pain and Soreness Scale
Stanford Exercise Behavior Scale
Self-reported questionnaire
o POMS Questionnaire: Subjects will complete the questionnaire at this
visit.
Retrieval Procedures: Subjects will be asked to mail back any used/unused study product
and their containers.

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11. INVESTIGATIONAL STUDY PRODUCT

11.1 PRODUCT IDENTITY / DOSING
This investigational product is manufactured under dietary supplement GMP.
11.1.1 Statinzyme Study Product
INSTRUCTION: Take two capsules with food, twice daily for the first four weeks. Then take
two capsules with food once a day for the remainder of the study.
ACITVE INGREDIENTS: VITAMIN B6, FOLIC ACID, VITAMIN B12, VITAMIN D,
FISH OIL (EICOSAPENTAENOIC ACID, DOCOSAHEXAENOIC ACID), FLAX SEED
OIL, EVENING PRIMROSE OIL, COENZYME Q10, RESVERATROL
INACTIVE INGREDIENTS: NATURAL VITAMIN E OIL, BEESWAX, SOYBEAN OIL,
GELATIN, GLYCERIN, PURE WATER

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11.2 STORAGE
Investigational products are stored at room temperature.
The study product is to be stored in accordance with the manufacturer's instructions, i.e. in a dry
place and at room temperature. The study product must be kept out of the reach of children. This
study product may not be used after the expiration date has been reached
Important note: Investigational products are only allowed to be administered to subjects
selected for this clinical study.
11.3 PACKAGING AND DISPENSING
Sponsor will provide the CRO with sufficient study products to complete this study. The CRO
will distribute the study products to the subjects home address in a Study Product Container
(SPC) according to each subjects assignment.
The investigator will confirm receipt of the investigational products in writing and will use the
investigational products only within the framework of this clinical study and in accordance with
the study protocol. All study products are to be used only for this protocol and not for any other
purposes. Subjects are instructed to store the products in a dry place at room temperature, as
stated in the product label. All unused or returned study products should be returned to the
sponsor.

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11.4 LABELLING
Each study product container (SPC) will contain 2 perforated labels. One label adhered to the
SPC while one will be detached and placed into the CRFs. The labels will contain:

Study code number

Patient number
Directions of use
Storage Instructions
Date and Quantity Dispensed
Date and Quantity Returned

PRODUCT LABEL Statinzyme Study Product

Prescription Vitamins, LLC

Study ID: STAT1200

Investigator:
Enrollment #:

SUBJECT ID:
DATE DISPENSED:
DATE RETURNED:

Site:
ARM

Bottle#:

Site Phone: 844-324-3777

SUBJECT INITIALS:
QTY DISPENSED:
QTY RETURNED:

Take two capsules with food, twice daily for the first four weeks. Then take two capsules with food once a
day for the remainder of the study.
Store the product in a dry place at room temperature.
Please return both used and unused study product container on
completion of study.
Keep out of reach of children
Batch:

Manufactured Date:

FOR CLINICAL TRIAL USE ONLY

NO COMMERCIAL VALUE

Exp Date:

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11.5 ACCOUNTABILITY
The sponsor will deliver the study product to the CRO (Medicus Research, LLC Agoura Hills,
California). The CRO will deliver the study product to the subjects home address.
All study products are to be stored appropriately, and shall be kept in a secure place until
dispensed. Access is restricted to the Study Investigator and designated personnel. Study
products shall only be used for this study, and shall only be dispensed to subjects who are
enrolled in this study and who, per protocol, are scheduled to receive the study product.
The clinical research site must maintain inventory records of the study products. Records must
be made available to the sponsor, and to representatives of regulatory and other governmental
bodies, as required by law, regulation or contractual agreement.
All unused study products shipped to the subject for this clinical trial will be returned to the
CRO. All used investigational study products, including empty containers as well as all unused
study products will then be returned to the CRO at the following address:
Medicus Research
Attn: Inventory Department
28720 Roadside Drive, Suite 310
Agoura Hills, CA 91301
818-882-9442
At the conclusion of the study, the Investigator or an appropriate designee, and the CRO
representative will inventory all used and unused investigational study products. The study
product inventory record for returned study products will then be completed. Unused products
will be returned to the sponsor. Upon receipt by the sponsor, the sponsor will send written notice
to the CRO to acknowledge the receipt of returned materials. The sponsor will retain the
original, and the clinical site(s) and CRO will retain copies for their files.
11.6 DISPENSING
The product will be received from the sponsor.
Products will be dispensed from the CRO to the subjects homes. A CRO product accountability
log will be utilized to track all dispensing of the product to the study sites.
All dispensing will be recorded on the site product dispensing log and in the CRF.

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11.7 CONCOMITANT MEDICATION

11.7.1 Prohibited Medications and Interventions
The following products and interventions are not permitted while the patient is on this
Study:
Any Allowed Medications and Interventions
All medications and non-medicinal interventions shall be recorded during the entire study
period.
The following products will be permitted during the study and must be recorded on the
appropriate Study Case Report Form(s):

Hormonal Contraception, including oral, patch, or devices (e.g., hormonal

rings or IUDs).

On each visit new concomitant medications or changes of concomitant medications must

be documented. This will be recorded by the virtual clinic study staff every visit.

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12. DATA ANALYSIS AND STATISTICAL METHODS

12.1 ENROLLMENT
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will be enrolled in
the study.
After the subject has completed the online screening visit (V1) and the telephone screening visit
(V1.5) and has met all of the inclusion criteria and none of the exclusion criteria, the subject will
be assigned the next available enrollment ID.
12.2 DATA MANAGEMENT
The monitoring team will ensure that the subjects are compliant. Parallel dual data reconstruction
and transformation will be done by data management personnel across all endpoints. Data
validation and reconciliation of parallel transformation will occur after the dual data
transformation process. Data files will be password-protected by the data management team for
data integrity and confidentiality purposes prior to any analyses made by the Biostatisticians.
12.3 EXAMINATION OF DATA
All data elements will be screened for reasonableness, and all missing, suspicious, or impossible
values will be referred back to the monitoring team for query generation and resolution. All
numerical variables will be tested for normality, and data found to be substantially non-normally
distributed will be analyzed by appropriate non-parametric methods.
12.4 DATA LOCK AND UNBLINDING
After all suspicious entries in the database have been resolved; a data lock form will be signed by
the Head of Scientific Data Management and Analysis team to formally lock the database.
Locked database will be free from any changes on the data sources and data entries. Data unlock
form should be issued and signed if there will be changes needed to reflect or integrate on the
database.

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12.5 DESCRIPTIVE SUMMARIZATION

All variables under investigation will be summarized by time point. Endpoints in interval/ratio
scale will be presented as (n, mean, standard deviation and standard error). Numerical variables
will also be presented graphically, as plots of average value versus time.
For each endpoint in at least ordinal scale, the differences between time periods for each product
group will be tested for nominal significance using non-parametric test (Wilcoxon Signed Rank
Test or Sign Test). Difference in the distribution between arms will be tested using nonparametric Chi-square Test.
For those numerical endpoints that were found to have normally distributed data, comparison
between products will be assessed using Independent t-test for group differences at each time
point and paired sample t-test will be used to assess within-group changes from baseline to each
subsequent time points. For non-normally distributed numerical endpoints, Wilcoxon MannWhitney test, for comparison between products to asses between group differences at each time
point and Wilcoxon Signed Ranks test or Sign test will be used to assess within-group changes
from baseline to each subsequent time points.
All tests of hypotheses will be done at alpha=0.05.
12.6 COMPLIANCE CALCULATION
Compliance will be calculated, as follows:
% Compliance = (Number of study product consumed/Number of days since last visit) x 100
Compliance will be adjusted if dose titration is used.
12.7 STATISTICAL HYPOTHESES
The null hypotheses tested for this study are the following:

There were no significant changes in the VAS Pain and Soreness Scale, Stanford Exercise
Behavior Scale, and Self-Reported questionnaire from Baseline to other time points.

There were no significant changes in the POMS questionnaire from Baseline to other
time points.

12.8 STATISTICAL ANALYSIS

Statistical Software for Social Sciences (SPSS version 19) will be used to run all descriptive and
inferential analyses for all endpoints.
Efficacy Analysis

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A Modified per Intend to Treat (Mod ITT) analysis will be performed to assess the efficacy
variables of the study. Subjects with at least one post-dose visit completed will be included
in the analysis.
The primary objectives of this study are; to determine the healing time of cold sores is half
of that of historical data on untreated cold sores, to determine the healing time cold sores is
less that of placebo, to assess the efficacy of Lysine+ in providing relief of cold sore
symptoms, to assess the efficacy of Lysine+ in aborting cold sore episodes, and to
determine the end of study marketing questionnaire.
All numeric/continuous efficacy variables will be tested for normality and will be analyzed
by Analysis of Covariance (ANCOVA). In the analysis, the value of the efficacy variable at
every time point will be modeled as a function of the treatment group (predictor variable of
interest) and of the value of that efficacy variable at Baseline (covariate). The analysis will
result to significant efficacy if the coefficient of the treatment group variable is
significantly different from zero and in the right direction.
The ANCOVA approach is used to mathematically compensate for the subjects baseline
characteristics that happen to be substantially unbalanced between the two treatment
groups. It is more efficient than the simpler Student t-test since it adjusts for possible
situation like regression to the mean and floor effects.
Data transformation will be used to utilize ANCOVA approach for residuals of the raw data
that were found to be substantially non-normally distributed.
Safety Analysis
To obtain comparable documentation on AEs, the investigator will ask the subject a set of
open and standardized questions at each visit. Frequency and intensity of AEs and serious
AEs will be recorded in detail, based on the subjects interviews during each visit.
Recorded AEs will be grouped by general type of event. Differences in AE patterns
between product groups will be assessed by Fisher Exact test.
12.9 CONTROL OF INFERENCE ERRORS
Hypothesis testing for each of the efficacy endpoints under investigation will be tested at
alpha=0.05. In terms of interpreting statistical results, for each specific endpoint, there is a 5%
chance of rejecting the null hypothesis when in fact the null hypothesis (no significant
difference) is true. In this case, we may have a false positive result which indicates that even in
the absence of true efficacy with respect to a particular endpoint, probability of achieving
nominal significance will increase.
12.10 ANALYTICAL POPULATIONS
The Modified per Protocol (Mod PP) population consists of all subjects randomly assigned to
one of the treatments will be analyzed together, regardless of whether or not they completed the
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whole study duration. It ignores non-compliance, protocol deviations, withdrawal, and anything
that happens after randomization.
12.11 FINAL REPORT AND FINAL RESEARCH CLOSEOUT BINDER
After data analysis, final clinical study report will be provided by the CRO to the sponsor. The
CRO will summarize the results which accurately reflect the clinical data of this study.
All essential documents which includes CRFs, study materials, adverse event pages for each
subject, protocol deviations, database, and the Final report will be enclosed in a Final Research
Closeout binder. The binder serves as a repository of the overall study process.

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13. ADMINISTRATION
13.1 DOCUMENTATION, RECORD ACCESS AND ARCHIVING
All subjects who have given their permission for study participation, regardless of whether the
subject has received any investigational product(s) or not have to be entered on the subject
log by the investigator/investigators designee. The subject identification list will allow an
unambiguous identification of subjects who are taking/took part in this study and will be kept in
the Investigators Study File and archived for at least 5 years.
13.2 DATA PROTECTION
All local legal requirements regarding protection of personal data will be followed.
The investigator/investigators designee will assign a subject number to each study subject,
which will be used for subject identification whenever subject related data are recorded for the
sponsor or reported. Throughout all steps of documentation and evaluation, the subjects will be
identified on CRFs and other documents by date of birth and subject number (pseudonymous).
Documents in which the subject name is identified (e.g. the signed Informed consent), must be
maintained in confidence by the investigator in a locked cabinet in a limited access room.
Identity and personal data will be treated as confidential, but may be subject for review by
authorized representatives of the CRO (monitor, project manager), independent auditors,
IRB/IEC and regulatory authorities. The monitors are entitled to compare paper CRF entries with
the protocol and with transcribed electronic CRFs and to inform the investigator about errors
and omissions.
13.3 ESSENTIAL DOCUMENTS
Prior to initiation of the study center, an Investigators Study File will be compiled for the
study center by the CRO. The investigator must maintain and update the essential study documents specified in chapter 8 of the ICH-Guideline for Good Clinical Practice and as required by
applicable national regulatory provisions in the Investigators Study File.
The investigator must assure that the Investigators Study File is archived for at least 5 years and
that these documents are not prematurely discarded.
13.4 CASE REPORT FORMS (CRFS), DIARIES
For each subject, the investigator must enter or attach in the CRF all requested data and findings,
as they become available during the study. The CRFs are designed to record all the data required
by this protocol. For each subject enrolled into the study, a CRF must be completed. The CRFs
should be completed legibly, using a black ballpoint pen and must be signed by the investigator.
The CRFs should be available at all times for monitoring visits.
Standardized paper and electronic CRFs provided by the CRO will serve as the complete source
documentation for this study.
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13.5 ARCHIVING
The investigator must archive all essential documents of this clinical study including CRFs for a
minimum period of 5 years after regular study end or after premature discontinuation of the
study (if applicable) in accordance with ICH.

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14. ADMINISTRATIVE PROCEDURES

14.1 AMENDMENTS TO THE PROTOCOL
Should any relevant change be required to the signed, final protocol, a protocol amendment will
be required. Relevant change is defined as any consistent change that deviates from the
procedures as outlined in the protocol will require an amendment. This decision is made by the
investigator. The amendment must be signed by the principal investigator, the project managers
of the sponsor and the CRO, and, if necessary, by the statistician. If those amendments are
substantial and are likely to have an impact on the safety of the trial subjects or they change the
interpretation of the scientific documents in support of the conduct of the trial, or if they are
otherwise significant, the sponsor will notify Ethics Committee/s (IRB/IEC) concerned. The PI
must submit an amendment request to the IRB and receive written approval prior to
implementation of any change to the protocol.
14.2 DISCLOSURE OF ALL INFORMATION AND RESULTS
All information concerning the results derived from the study and the investigational product are
regarded as confidential. Prior to publication of the study results, the investigators and members
of their research teams are not permitted to disclose any such information. By his signature the
investigator(s) agree(s) to keep the data confidential.
14.3 PUBLICATION
After data analysis, the CRO will summarize the results in a final report which accurately reflects
the clinical data of this study.
If publication is decided in the future, a discussion will be held with the sponsor to determine the
appropriate medium. Any publication of the trial data will be wholly consistent with the
integrated final report in accordance with the ethical principles of the Declaration of Helsinki.

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15. PROTOCOL IMPLEMENTATION

This protocol was developed according to ICH-GCP guidelines (CPMP/ICH/135/95) and to the
standards of the CROs SOPs.
15.1 PROTOCOL MODIFICATIONS
In the event that a modification of the protocol becomes necessary, due to safety, subject accrual
or other considerations, the changes will be reviewed by both the Sponsor and IRB, and when
necessary, reviewed and approved by the FDA. No changes shall be implemented until
appropriate review and approval has been received, except when necessary to eliminate an
immediate hazard(s) to the study subjects.
15.2 PROTOCOL DEVIATIONS
Deviations to the protocol must be documented on the appropriate CRF and reported to the
Sponsor. The clinical site will maintain documentation of the dates and reasons for each
deviation from the protocol, in compliance with 21 Code of Federal Regulations (CFR) 312.60.
Deviations must be reported to the IRB at closeout or at continuing review.
15.3 QUALITY ASSURANCE AND QUALITY CONTROL
The Sponsor and the CRO are responsible for implementing and maintaining quality assurance
and quality control systems with written SOPs according to the Guidelines of Good Clinical
Practice (CPMP/ICH/135/95). Quality control will be applied to each stage of data handling.
The CRO's adherence to quality standards may be inspected by means of independent audits.
15.4 MONITORING
Monitoring will be performed in accordance with the stipulations of Chapter 5.18 of the
ICH GCP Guideline. The study will be monitored by the CRO monitoring staff.

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16. FINAL REPORT

A final clinical study report will be provided by the CRO to the sponsor. A final report must be
submitted to the IRB to close out the study.

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17. ADVERSE EVENTS AND SAFETY ASPECTS

Clinical safety data management (definitions and reporting) is in accordance with:
FDA 21 CFR part 312

CPMP guideline causality classification in pharmacovigilance.

Note for guidance CPMP/ICH/377/95

Detailed guidance on the collection, verification, and presentation of AR reports

Subjects will be assessed for their ability to tolerate the assigned Study Drug. Each subject shall
complete a daily Study Diary. Subjects are encouraged to describe their experiences, along with
recording of their daily doses, and description of any concomitant medications or interventions
that they use.
17.1 DEFINITION OF ADVERSE EVENT
An adverse event (AE) is defined as any untoward, undesired, or unplanned event in the form
of signs, symptoms, diseases, or laboratory or physiologic observations occurring in a subject
who has signed an ICF. This includes AEs which may occur during screening and baseline, i.e.
prior to treatment with investigational product. If there is any doubt whether the information
constitutes an AE or if the information will be treated as an AE.
The event does not need to be causally related to the product or this clinical study. This includes:
a. Any clinically significant worsening of a pre-existing condition. (A pre-existing
condition is a clinical condition [including a condition being treated] that is diagnosed
or identified before the patient signed the Informed Consent Form and that is
documented as part of the patients medical history.)
b. An adverse event occurring from overdose (an overdose will be considered to be a
total daily dose higher than the highest dose tested in this protocol) of the Study
product, whether accidental or intentional;
c. An adverse event occurring from abuse (e.g., use for non-clinical reasons) of the study
products;
d. An adverse event that has been associated with discontinuation use of the study
products (i.e. subject non-compliance)
A procedure that a study patient may undergo (e.g., surgery) is not classified as an adverse event,
but the reason leading to the procedure may be an adverse event.
17.2 DEFINITION OF SERIOUS ADVERSE EVENT
A Serious Adverse Event (SAE) is any medical and scientific judgment that must be exercised
when classifying events as serious. Serious adverse events will be collected throughout untoward
medical occurrence at any dose:

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a. Results in death
b. Is life-threatening (refers to an event in which the patient was at risk of death at the time
of the event. It does not refer to an event which hypothetically might have caused death if
it were more severe.)
c. Requires hospitalization or prolongation of existing hospitalization.
d. Requires significant intervention to prevent a serious outcome outside of a hospital
setting (e.g. intensive treatment in an emergency room or at home for allergic
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization).
e. Results in persistent or significant disability/incapacity of the study and must be followed
until resolution (e.g., death, resolved, stable with or without intervention).
17.3 DETERMINATION OF THE LIKELIHOOD OF CAUSALITY
When assessing the likelihood that an adverse event is causally related to an investigational
product or protocol, the following parameters will be considered:
a. Temporal relationship between the investigational product/protocol and the adverse
event;
b. Biologic plausibility of relationship;
c. Patients underlying clinical state or concomitant agents/therapies;
d. Where applicable, does the event abate on discontinuation of the investigational
product (i.e.,dechallenge);
e. Where applicable, does the event reappear on repeat exposure to the investigational
product (i.e., rechallenge).
The following definitions will be used to assess relatedness of an adverse event:
Definite

A reaction that follows a plausible temporal sequence from administration

of the product, and follows a known response pattern to the suspected product
and can be confirmed with a positive re-challenge test or supporting
laboratory data.

Probable A reaction that follows a plausible temporal sequence from administration of

the product and follows a known response pattern. The AE cannot be
reasonably explained by the known characteristics of the patients clinical
state.
Possible

A reaction that follows a plausible temporal sequence from administration of

the product and follows a known response pattern. The AE may also have
been produced by the patients clinical state.

Remote

The current state of knowledge indicates that a relationship is unlikely.

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None

No relationship between the experience and the administration of study

product; AE is related to other etiologies such as concomitant medications or
patients clinical state (i.e. due to intercurrent potential illness (es).

17.4 MONITORING OF ADVERSE EVENTS

Subjects will be interviewed in a non-leading way at every study visit to identify potential
adverse events. The standard inquiry is Have there been any changes in your health since your
last visit? The occurrence of an adverse event will be based on the changes in the subjects
physical examination, laboratory results, and/or signs and symptoms. Adverse events will be
recorded throughout administration of the investigational product and following cessation of the
test product in a case report form (CRF). Toxicity and adverse events will be assessed using the
WHO/NCIC (adapted) Toxicity Scale.
Whenever feasible, signs and symptoms indicating a common underlying pathology should be
noted as one comprehensive event. AEs of a suspected, probable, missing or unknown causality
will be assessed as treatment-related adverse drug reaction. Individual AEs will be scored and
grade per Toxicity Scale. But, in addition to this, the Study Physician should also write a brief
narrative that assesses the AE.
17.5 REPORTING REQUIREMENTS
Recording Periods for Serious and Non-Serious Adverse Events
The recording period for a serious adverse event starts at the time the patient signs the study
Informed Consent Form. This includes events that emerge during screening and at baseline. The
recording period for a non-serious adverse event starts at the time after which the subject takes
the first dose of Study product.
The recording period for both serious and non-serious adverse events lasts through 28 days after
the subjects last administration of study product, regardless of relationship to the study product
or protocol. The Clinical Coordinator must follow up as medically necessary on all adverse
events, serious adverse events, and other reportable events until the event has subsided or values
have returned to baseline, or in the case of permanent impairment, until the condition stabilizes.
Information about all adverse events, serious and non-serious, including the events severity, start
and stop times/dates, chronicity, relatedness to study product, and any actions taken, must be
recorded on the appropriate case report forms. The information recorded will be based on signs
and symptoms detected during the physical examination and clinical evaluation of the patient, in
addition to information recorded in the Study Diaries.
Serious Adverse Event (SAE) Reporting
Any serious adverse event which occurs during the course of the study and that could affect the
safety of the study participants or the conduct of the study, whether or not related to the
investigational product, must be immediately (i.e. within 24 hours) reported to the CRO, who
will inform the Sponsor or Sponsors designee. The (preliminary) information must contain at
least the following data:
Identification of the reporting investigator:
Name, institute, address, telephone number, fax, email, etc.
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Identification of the study:

Study code or title, respectively, investigational product(s)
Identification of the patient:
Assigned 3-digit patient number, sex and date of birth.
Description of the Serious Adverse Event/serious adverse reaction:
Symptoms/diagnosis, therapeutic measures taken, outcome as far as already known,
causal relationship.

This information can be transmitted via telephone, fax, or email. In the case of a phone report,
this preliminary report will be written by the CRO according to the information given and signed
by the CRO.
The investigator should provide a final report within a reasonable time after the initial report,
depending on the duration of the event and availability of evaluations and reports of third parties.
The investigator must forward the SAE report form by fax to the CRO or the sponsor who will
inform each other. The original of the SAE report form will then be collected by the CRO and
sent to the sponsor. The investigator should report the SAE to the IRB within 10 days of
discovery.
In the event of the death of a trial subject, the investigator shall supply the sponsor and the Ethics
Committee with any additional information requested. Personal data must be pseudonymised
prior to being communicated by using the screening number of the trial subject.

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18. PREMATURE DISCONTINUATION

Premature discontinuations are defined as subjects who do not complete the study as required by
the study protocol either at their own request or at the request of the investigator.
The subject is entitled to terminate the study at any time without giving any reasons and without
having to expect any disadvantages. However, the investigator should try to find out and document
the reasons for a premature discontinuation. The investigator can stop the participation of a subject
as well, or the entire study in her/his study center, after consideration of the benefit/ risk ratio.
Subjects with abnormal data sets may also be evaluated during interim analysis and be removed
from the study. This is appropriate as long as the decision is made prior to knowing which
randomization group the subject is part of and helps ensure reliability of the data set. The statistical
team reserves the right to remove outlier data from the analysis before un-blinding, which is based
on the discretion of the researchers.
Study Drop Out
Subjects who are randomized, but drop out prior to completing the study will be recorded. A record
of reasons why subjects drop out of the study will be maintained. All data from registered subjects
who took at least one dose of the study products and who subsequently dropped out shall be
included in the safety analysis.
Screening Failures
Screening failures are defined as those subjects who appeared at visit 1, who consented to
participate in the study by signing study specific informed consent documents, and who otherwise
were deemed ineligible to participate in this study. A record of screened subjects and reasons for
ineligibility will be maintained.
Patient Termination or Withdrawal
In the event of study discontinuation the following data will be recorded:
Date of the latest treatment under the study
Date and time of the latest contact between investigator and patient
Reason for decision to discontinue

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19. REGULATORY AND ETHICS

19.1 ETHICAL CONDUCT OF THE STUDY
The Guidelines of the World Medical Association's Declaration of Helsinki in its revised edition
of 1996 1 and the Guidelines of Good Clinical Practice (CPMP/ICH/135/95) will be adhered to2.
19.2 INSTITUTIONAL REVIEW BOARD (IRB)
Prior to the initiation of the study, this protocol including the Informed Consent Form will be
submitted to the independent IRB and the trial will not start until unconditional approval is
received.
19.3 SUBJECT INFORMED CONSENT
The investigator/investigators designee must explain the study fully to the subject. The Informed
Consent document must be provided to the subject in paper or in an electronic form that is
understandable for the subject. The Informed Consent must be presented to the subject both
verbally and electronically, and is intended to serve as a basis for the explanation of the study by
the investigator. This will be performed via an electronic signature on the online consent form
and will be verbally verified by the study staff. With signing the Informed Consent document, the
subject agrees equally that data collected during the course of the study may be passed on in a
pseudonymous manner to the appropriate authorities and to the sponsor. The CRO will provide
the investigator with a sufficient number of copies of the approved subject information and
Informed Consent Forms.
The informed consent process involves an online infographic presentation detailing all of the
components of the study. Following this, an electronic signature will be recorded by the subject,
confirming that they understand the study procedures as detailed in the online consent document.
In addition, verbal consent will be obtained by the virtual clinic team during the telephone
screening that follows the online screen.
The investigator/investigators designee will not undertake any study-related investigations with
any specific subject prior to obtaining written Informed Consent.
Subjects who refuse to sign the Informed Consent or who do not agree to recording and reporting
their pseudonymous data to required authorities may not be included in this study. Subjects who
withdraw Informed Consent may not continue in the study (discontinuation).
The content of the written subject information and Informed Consent will be in accordance with
the Guidelines of Good Clinical Practice (CPMP/ICH/135/95) and 21 C.F.R Part 50, Subpart B.
Sufficient time will be allowed to discuss any questions raised by the subject about the informed
consent. The Informed consent form must be electronically signed and dated by the subject and
verified verbally by the Investigators designee, who reviewed the Informed Consent Document
with the subject during the remote visit. The investigator must retain the record of the
electronically signed document as part of the study records.

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The Informed Consent Form will be kept and archived by the investigator in the "Investigator's
Study File". The terms of the Informed Consent Form and the date when it was obtained should
be entered in the CRF.
19.4 REQUIREMENTS BY THE INVESTIGATOR(S) AND THE STUDY CENTER
The investigator should make him or herself thoroughly familiar with the properties of the study
medication, which are described in the Investigators Brochure.
He/she should make sure that he/she has enough time to carry out the study, that sufficient staff
and adequate facilities are available for the complete duration of the study, and that the planned
number of subjects can be recruited within the proposed period of time.
He/she must provide the sponsor with up-to-date curriculum vitae for documentation purposes.
He/she must approve the protocol in all its details and signs it together with the sponsor. He/she
must confirm in writing that he/she has read and understood the protocol, that he/she will work
in compliance with the protocol, Good Clinical Practice and the legal regulations, that he/she will
permit monitoring, auditing and inspections, and that he/she will come to an agreement with the
sponsor about publication.
He/she must fully inform all of his/her staff members who are involved in carrying out the study
or involved in subject care. Any delegated study tasks must be documented in writing.
He/she must organize a system to ensure that the deliveries of the investigational products from
the sponsor will be correctly received by a responsible person, that the deliveries will be
registered, that the study products will be safely and correctly handled and stored, that it will
only be distributed to subjects participating in the study in accordance with the protocol, and that
unused study products will be returned to the sponsor. At the end of the study, documentation
must be made available to ensure correct accountability of the study products delivered by the
sponsor on one hand, and the used and/or unused study products, on the other hand all
discrepancies must be accounted for delivery and return forms must be signed.
He/she must explain all aspects of the study to the subject in a comprehensible manner, as given
in the written subject information, and he/she will inform the subject in due time of any new
particulars that could influence the subjects willingness to participate in the study. The fact that
the investigator has given this information; it must be documented in writing.
He/she must give the subject an ample opportunity to ask questions, and he/she will allow the
subject sufficient time to reach a decision regarding participation. The investigator will provide
the subject a copy of the signed Informed Consent.
He/she must disclose any possible financial or other interests with the sponsoring company or the
investigational product.

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REFERENCE LIST

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APPENDIX 1: STANFORD EXERCISE BEHAVIOR SCALE

STANFORD EXERCISE BEHAVIOR SCALE
Version 1.1

During the past week, even if it was not a typical week for you, how much total time (for the entire
week) did you spend on each of the following? (Please circle one number for each question.)
Exercise Behaviors
1. Stretching or strengthening exercises (range
of motion, using weights, etc.)
2. Walk for exercise
3. Swimming or aquatic exercise
4. Bicycling (including stationary
exercise bikes)
5. Other aerobic exercise equipment
(Stairmaster, rowing, skiing machine, etc.)
6. Other aerobic exercise
Specify_________________________

None

Less than
30
min/wk

30-60
min/wk

1-3 hrs
per week

More
than 3
hrs/wk

0
0

1
1

2
2

3
3

4
4

APPENDIX 2: VAS PAIN AND SORENESS SCALE

Assign a number from 0 (zero) to 10 (ten) to your pain level. If you have no pain, use a 0. As the
numbers get higher, they stand for pain that is getting worse. A 10 means the pain is as bad as it can be.

APPENDIX 3: MOBILE APPLICATIONS

APPENDIX 4: POMS

POMS
Version 1.2

Please fill in the information below:

Age:

Birthdate:
(mm-dd-yyyy)

Gender: Male

Female2

Today's date:
(mm-dd-yyyy)

--
--

Below is a list of words that describe feelings that people have. Please read each word carefully.
Then place a check in the box next to the number that best describes how you feel RIGHT NOW.
NOT AT ALL0

1. Friendly
2. Tense
3. Angry
4. Worn out
5. Unhappy
6. Clear-headed
7. Lively
8. Confused
9. Sorry for things done
10. Shaky
11. Listless
12. Peeved
13. Considerable
14. Sad
15. Active
16. On edge
17. Grouchy
18. Blue
19. Energetic
20. Panicky
21. Hopeless
22. Relaxed
23. Unworthy
24. Spiteful
25. Sympathetic
26. Uneasy
27. Restless
28. Unable to concentrate
29. Fatigued
30. Helpful
31. Annoyed
32. Discouraged
33. Resentful
34. Nervous
35.Lonely
36. Miserable
37. Muddled
38. Cheerful
39. Bitter
40. Exhausted
41. Anxious
42. Ready to fight
43. Good natured
44. Gloomy
45. Desperate

A LITTLE1

MODERATELY2 QUITE A BIT3 EXTREMELY4

APPENDIX 5: PHONE SCREEN

SUBJECT NAME
SUBJECT CONTACT INFORMATION

SUBJECT'S FULL NAME

(XXX) XXX-XXXX
EMAIL@DOMAIN.COM
RECRUITER
DATE
YOUR NAME
MM/DD/YYYY
AS I AM ASKING YOU QUESTIONS IN REGARDS TO YOUR HEALTH AND MEDICAL HISTORY, YOU MAY
STOP ANSWERING QUESTIONS AT ANY TIME. YOU DO NOT HAVE TO ANSWER ANY QUESTIONS THAT
MAKE YOU FEEL UNCOMFORTABLE. MAY I PROCEED WITH THE SCREEN?
DOB
AGE
HEIGHT
WEIGHT
BMI