Clinical trial NCT03532776
Conditions: External Anogenital Warts
Sponsor: Dermax SA
Start date: 2018-04-20; Completion date: 2020-01-31
Enrollment: 466 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A clinical endpoint bioequivalence (BE) study for a Podofilox Gel 0.5% formulation for the treatment of external anogenital warts in comparison to Condylox® Gel 0.5% that follows the study design and recommendations according to Office of Generic Drugs (OGD) of U.S. Food and Drug Administration (FDA) Draft Guidance for Podofilox recommendations

Detailed description:
This is a multicenter, parallel group, randomized, double-blind, placebo-controlled, trial with clinical endpoint comparing Podofilox Topical Gel 0.5% to Condylox® Gel 0.5% and a matching placebo. The study will be conducted among adult male and female patients with external anogenital warts. The Investigator will assess vital signs and perform physical examination identifying any clinically significant abnormalities. Laboratory samples will be collected, including HIV, Hepatitis B\&C, and urine pregnancy tests (UPT) for women of childbearing potential. The Investigator will confirm the diagnosis of External Anogenital Warts (EAW) and the absence of contraindications specified in the exclusion criterion 4 during the visual examination. The biopsy of skin lesions will be performed per the discretion of the Investigator for microscopic verification of the diagnosis of EAWs if any doubts of the diagnosis.

Arms: arm 1: Podofilox Gel 0.5% twice a day, three days following by four days of discontinuation, up to four cycles arm 2: Condylox Topical Gel 0.5% twice daily, three days following by four days of discontinuation, up to four cycles arm 3: Subjects in this arm will receive a vehicle that matches the test product, except for the inclusion of the active ingredient
Interventions: intervention 1: Podofilox Gel 0.5% intervention 2: Condylox Topical Gel 0.5% intervention 3: Placebo Gel
Intervention descriptions: intervention 1: Apply twice daily for three consecutive days, then discontinuing for four consecutive days, up to four treatment cycles intervention 2: Apply twice daily for three consecutive days, then discontinuing for four consecutive days, up to four treatment cycles intervention 3: Apply twice daily for three consecutive days, then discontinuing for four consecutive days, up to four treatment cycles

Protocol documents:
Prot_000.pdf: 
Protocol Number: 016-POD-001 
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A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PARALLEL 
GROUP, PLACEBO-CONTROLLED STUDY OF HYLORIS 
DEVELOPMENT’S PODOFILOX TOPICAL GEL 0.5% COMPARED TO 
ALLERGAN’S CONDYLOX® GEL 0.5%, AND BOTH ACTIVE 
TREATMENTS TO A VEHICLE CONTROL IN MALE AND FEMALE 
PATIENTS WITH EXTERNAL ANOGENITAL WARTS 
Protocol Number: 
016-POD-001 
Development Phase: 
Phase 3 
Sponsor: 
Hyloris Developments SA 
Bâtiment GIGA EE1 
Avenue Hippocrate n° 5 
4000 Liège (Sart-Tilman) 
Belgium 
Protocol Version: 
2.0 




Protocol Number: 016-POD-001 
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INVESTIGATOR SIGNATURE PAGE 
I have read and agree to the protocol 016-POD-001, entitled, “A Multicenter, Randomized, Double-Blind, 
Parallel Group, Placebo-Controlled Study of Hyloris Development’s Podofilox Topical Gel 0.5% compared 
to Allergan’s Condylox® Gel 0.5%, and Both Active Treatments to a Vehicle Control in male and female 
patients with external anogenital warts” (Version 2.0, dated 15 January 2018). I am aware of my 
responsibilities as an Investigator under the guidelines of GCP, FDA regulations, local regulations (as 
applicable) and the study protocol. I will conduct this study in strict accordance with this protocol, 
ICH Guidelines for Good Clinical Practices, the Code of Federal Regulations, the Health Insurance 
Portability and Accountability Act (HIPAA) and any local regulatory requirements and will 
attempt to complete the study within the time designated.  I will provide access to copies of the 
protocol and all other information relating to pre-clinical and prior clinical experience submitted 
by Perrigo to all personnel responsible to me who participate in the study.  I will discuss this 
information with them to assure that they are adequately informed regarding the drug and conduct 
of the study.  I agree to keep records on all subject information in accordance with applicable local 
and FDA regulations. 
 
Clinical Site:  
 
 
 
Clinical Site 
Address 
 
 
 
Site Principal Investigator: 
 
 
 
 
Print Name 
 
Title 
 
 
 
 
 
Signature 
 
Date 
 


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TABLE OF CONTENTS 
SIGNATURE PAGE ................................................................................................................................ 2 
INVESTIGATOR SIGNATURE PAGE ................................................................................................ 3 
TABLE OF CONTENTS ......................................................................................................................... 4 
LIST OF ABBREVIATIONS .................................................................................................................. 8 
PROTOCOL SYNOPSIS....................................................................................................................... 10 
PRINCIPAL CONTACTS..................................................................................................................... 17 
1 
BACKGROUND AND RATIONALE .......................................................................................... 19 
1.1 
Background to the Disease ....................................................................................................... 19 
1.2 
Background to the Study Drug ................................................................................................ 22 
1.2.1 
Clinical Pharmacology .................................................................................................... 22 
1.2.1.1 
Mechanism of Action ................................................................................................. 22 
1.2.1.2 
Pharmacokinetics ....................................................................................................... 22 
1.2.2 
Clinical Experience.......................................................................................................... 22 
1.2.3 
Safety Profile ................................................................................................................... 23 
1.3 
Rationale of the Study ............................................................................................................... 23 
2 
STUDY OBJECTIVES AND ENDPOINTS ................................................................................ 24 
2.1 
Study Objectives ........................................................................................................................ 24 
2.1.1 
Primary Objective ............................................................................................................ 24 
2.1.2 
Secondary Objective ........................................................................................................ 24 
2.2 
Study Endpoints ........................................................................................................................ 24 
2.2.1 
Primary Endpoint ............................................................................................................. 24 
2.2.2 
Secondary Endpoint (Safety Endpoints) .......................................................................... 24 
3 
INVESTIGATIONAL PLAN ........................................................................................................ 25 
3.1 
Study Design .............................................................................................................................. 25 
3.2 
Number of Subjects and Sites................................................................................................... 26 
4 
SELECTION AND WITHDRAWAL OF STUDY POPULATION .......................................... 27 
4.1 
Eligibility Criteria ..................................................................................................................... 27 
4.1.1 
Inclusion Criteria ............................................................................................................. 27 
4.1.2 
Exclusion Criteria ............................................................................................................ 27 
4.2 
Withdrawal and Early Discontinuation .................................................................................. 28 
4.3 
Contraception and Pregnancy Avoidance Measures ............................................................. 29 
5 
STUDY DRUG ADMINISTRATION .......................................................................................... 30 
5.1 
Identity of Study Drug(s) .......................................................................................................... 30 


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5.1.1 
Formulation of Study Drug.............................................................................................. 30 
5.2 
Packaging and Labeling ............................................................................................................ 30 
5.3 
Storage of the Study Drug ........................................................................................................ 30 
5.4 
Reserve Sample Retention ........................................................................................................ 30 
5.5 
Treatment Assignment (Randomization) ................................................................................ 31 
5.6 
Blinding ...................................................................................................................................... 31 
5.7 
Treatment Administration........................................................................................................ 31 
5.7.1 
Study Drug Dispensation and Application ...................................................................... 31 
5.8 
Treatment Compliance ............................................................................................................. 32 
5.9 
Accountability, Destruction and Return of Study Supplies ................................................... 32 
5.10 
Prior, Concomitant and Prohibited Therapy ......................................................................... 33 
6 
STUDY PROCEDURES AND SCHEDULE OF ACTIVITIES ................................................ 34 
6.1 
Administrative Procedures ....................................................................................................... 34 
6.1.1 
Subject Informed Consent ............................................................................................... 34 
6.1.2 
Documentation of Screen Failures .................................................................................. 34 
6.2 
Study Procedures and Evaluations .......................................................................................... 34 
6.2.1 
Clinical Evaluations ......................................................................................................... 34 
6.2.1.1 
Subject Demographics ............................................................................................... 34 
6.2.1.2 
Medical history .......................................................................................................... 34 
6.2.1.3 
Concomitant Medication Recording .......................................................................... 35 
6.2.1.4 
Vital Signs .................................................................................................................. 35 
6.2.1.5 
Physical examination ................................................................................................. 35 
6.2.1.6 
Visual Examination of External Anogenital Warts .................................................... 35 
6.2.1.7 
Assessment of Local Application Site Reactions ...................................................... 36 
6.2.1.8 
Adverse Event Assessments ...................................................................................... 36 
6.2.2 
Laboratory Evaluations.................................................................................................... 37 
6.2.2.1 
Serology test for HIV ................................................................................................. 37 
6.2.2.2 
Test for Hepatitis B&C .............................................................................................. 37 
6.2.2.3 
Pregnancy test ............................................................................................................ 37 
6.2.2.4 
Test for Syphilis ......................................................................................................... 37 
6.2.3 
Subject Diary Card Review ............................................................................................. 37 
6.3 
Study Procedures ....................................................................................................................... 38 
6.3.1 
Visit 1: Screening (Day -14 up to -1) .............................................................................. 38 
6.3.2 
Visit 2: Baseline Visit (Day 0) ........................................................................................ 38 
6.3.3 
Visits 3-6 (Day 7 [Week 1], Day 14 [Week 2], Day 21 [Week 3], and Day 28 [Week 4])


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 ......................................................................................................................................... 38 
6.3.4 
End of Study / Early Termination (EOS/ET) visit........................................................... 39 
6.3.5 
Unscheduled Visit ........................................................................................................... 39 
7 
SAFETY DATA COLLECTION, RECORDING AND REPORTING .................................... 41 
7.1 
Definitions .................................................................................................................................. 41 
7.1.1 
Adverse Event ................................................................................................................. 41 
7.1.2 
Serious Adverse Events ................................................................................................... 41 
7.2 
Adverse Event Severity ............................................................................................................. 42 
7.3 
Causality of Adverse Events ..................................................................................................... 42 
7.4 
Adverse Event Collection Period ............................................................................................. 43 
7.5 
Adverse Event Reporting .......................................................................................................... 43 
7.6 
Reporting of Pregnancies .......................................................................................................... 44 
7.7 
Unblinding due to SAE ............................................................................................................. 44 
8 
DATA ANALYSIS .......................................................................................................................... 46 
8.1 
Subject Population/Data Sets to Be Evaluated ....................................................................... 46 
8.2 
Sample Size Determination....................................................................................................... 47 
8.3 
Statistical Analyses .................................................................................................................... 47 
8.3.1 
Subject Disposition and Demography ............................................................................. 47 
8.3.2 
Assessment of Bioequivalence as Primary Endpoint ...................................................... 47 
8.3.3 
Assessment of Superiority ............................................................................................... 48 
8.3.4 
Assessment of Safety ....................................................................................................... 48 
8.3.5 
Comparability of Subjects at Baseline ............................................................................. 49 
9 
STUDY CONDUCT ....................................................................................................................... 50 
9.1 
Ethical Conduct of the Study ................................................................................................... 50 
9.2 
Institutional Review Board (IRB) / Independent Ethics Committee (IEC) ......................... 50 
9.3 
Other Required Approvals ....................................................................................................... 50 
9.4 
Informed Consent ...................................................................................................................... 50 
9.5 
Subject Confidentiality ............................................................................................................. 51 
9.6 
Publication ................................................................................................................................. 51 
9.7 
Protocol amendments ................................................................................................................ 52 
10 ADMINISTRATIVE OBLIGATIONS ......................................................................................... 53 
10.1 
Source Documentation Forms .................................................................................................. 53 
10.2 
Record Retention ....................................................................................................................... 53 
10.3 
Quality Control (QC) and Quality Assurance (QA) .............................................................. 54 
10.3.1 
Study Site Monitoring Visits ........................................................................................... 54 


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10.3.2 
Protocol Deviations ......................................................................................................... 54 
10.4 
Trial Discontinuation/Investigative Site Termination ........................................................... 54 
10.4.1 
Criteria for Premature Termination or Suspension of the Study ..................................... 54 
10.4.2 
Criteria for Premature Termination or Suspension of Investigational Sites .................... 55 
10.4.3 
Procedures for Premature Termination or Suspension of the Study or Investigational 
Site(s) ............................................................................................................................... 55 
11 REFERENCES ............................................................................................................................... 56 
12 APPENDICES................................................................................................................................. 58 
12.1 
Appendix A. Study Flowchart .................................................................................................. 58 
12.2 
Appendix B. Schedule of Events .............................................................................................. 59 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BCA 
Bichloroacetic Acid 
BE 
Bioequivalence 
CDC 
Center of Disease Control 
CO2 
Carbon Dioxide 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CRF 
Case Report Form 
CV 
Coefficient of Variation 
DD 
Drug Dictionary 
DNA 
Deoxyribonucleic Acid 
EAW 
External Anogenital Warts 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EOS 
End of Study 
ET 
Early Termination 
FDA 
Food and Drug Administration 
g 
Gram 
GCP 
Good Clinical Practice 
H 
Hours 
HIV 
Human Immunodeficiency Virus 
HPV 
Human Papilloma Virus  
HSIL 
High-Grade Squamous Intraepithelial Lesions 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IP 
Investigational Product 


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IRB 
Institutional Review Board 
ITT 
Intent-To-Treat 
IRT 
Interactive Response System 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary of Regulatory Activities 
mITT 
Modified Intent-To-Treat 
OGD 
Office of Generic Drugs 
OTC 
Over-the-counter 
PD 
Protocol Deviation 
PMH 
Past medical history 
PI 
Principal Investigator 
PP 
Per-Protocol 
PRN 
Pro Re Nata (As Needed) 
QA 
Quality Assurance 
QC 
Quality Control 
RLD 
Referenced Listed Drug 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SOP 
Standard Operating Procedures 
STI 
Sexually Transmitted Infection 
Sub-I 
Sub-Investigator 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TCA 
Trichloroacetic Acid 
TEAE 
Treatment Emergent Adverse Event 
UPT 
Urine Pregnancy Test 
WHO 
World Health Organization 


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PROTOCOL SYNOPSIS 
Study Title 
A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-
Controlled, Study of Hyloris Developments’s Podofilox Topical Gel 0.5% 
compared to Allergan’s Condylox® Gel 0.5% in male and female patients 
with external anogenital warts 
Protocol Number 
016-POD-001 
Development Phase 
3 
Type of Study 
Bioequivalence (BE) with Clinical Endpoints 
Study Medication:  
1) Podofilox Topical Gel 0.5% (Test formulation), manufactured by 
Hyloris Developments 
2) Condylox® Gel 0.5% (Reference Product), manufactured by 
Allergan Pharmaceuticals 
3) Vehicle of test product, manufactured by Hyloris Developments SA 
Name of Active 
Ingredient 
Podofilox 
Route of 
administration 
Topical application 
Sponsor 
Hyloris Developments SA 
Bâtiment GIGA EE1 
Avenue Hippocrate n° 5 
4000 Liège (Sart-Tilman) 
Belgium 
Study Objectives 
PRIMARY 
• 
To compare the clinical efficacy among patients with anogenital 
warts when treated with Podofilox Topical Gel 0.5% or Condylox® 
Gel 0.5% or placebo. 
SECONDARY  
• 
To demonstrate safety of Podofilox Topical Gel 0.5% compared to 
Condylox® Gel 0.5% or placebo assessed by the frequency and 
severity of adverse events, and application site reaction scores 
(erythema, dryness, burning/stinging, erosion, edema, pain, itching 
and bleeding). 


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Study Design 
This is a multicenter, parallel group, randomized, double-blind, placebo-
controlled, trial with clinical endpoint comparing Podofilox Topical Gel 0.5% 
to Condylox® Gel 0.5% and a matching placebo. The study will be conducted 
among adult male and female patients with external anogenital warts.  
All study related procedures will be conducted only after written informed 
consent is obtained at the Screening visit, which will occur up to 14 days prior 
to the Baseline (Days -14 to -1). During the Screening visit, the Investigator 
will record subject’s demographics, medical history, review concomitant 
medication, identifying any prohibited therapies that subject is currently taking.  
The Investigator will assess vital signs and perform physical examination 
identifying any clinically significant abnormalities. Laboratory samples will be 
collected, including HIV, Hepatitis B&C and urine pregnancy tests (UPT) for 
women of childbearing potential. The Investigator will confirm the diagnosis 
of External Anogenital Warts (EAW) and the absence of contraindications 
specified in the exclusion criterion 4 during the visual examination. The biopsy 
of skin lesions will be performed per the discretion of the Investigator for 
microscopic verification of the diagnosis of EAWs if any doubts of the 
diagnosis. 
Once the results of Screening assessments are obtained, suggesting that the 
subject is eligible for entering the study, the Baseline visit (Day 0) will take 
place. During this visit, the Investigator will identify any AEs that occurred 
from the last visit, review concomitant and prohibited therapies, perform vital 
signs and physical examination. Those subjects who qualify for entering the 
study will be randomized to one of the following arms in a ratio of 3:3:1: 
• 
Arm 1 (Test product): Subjects in this arm will receive test formulation 
of Podofilox Topical Gel 0.5% (Hyloris Developments SA) 
• 
Arm 2 (Reference Listed Drug [RLD]): Subjects in this arm will 
receive RLD Condylox® Gel 0.5% (Allergan Pharmaceuticals) 
• 
Arm 3 (Placebo): Subjects in this arm will receive a vehicle that 
matches the test product, except for the inclusion of the active 
ingredient (Hyloris Developments SA) 
Randomization and study medication number assignment will be performed 
using an Interactive Response Technology (IRT) system that is fully 
integrated with the Electronic Data Collection (EDC) system. 
EAWs will be inspected and the count of EAWs will be captured in the source 
worksheet and electronic Case Report Form (eCRF). The Investigator will 
assess the baseline level of Local Application Site Reactions, recording the 
scores based on the Local Application Site Reactions Scale. 
During the inspection of EAWs, study physician (Principal Investigator (PI), 


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or Sub-Investigator) will train the subject on proper application of the study 
drug using the properly labeled demonstration tube (contains vehicle of the 
study drug) and applicator.  The subject will be trained to apply the study drug 
to the surface of the warts at a proper amount (not to exceed 0.5 g per day or 
0.25 g per application), avoiding unaffected and wounded skin areas, and to let 
the gel dry completely before allowing the return of opposing skin surfaces to 
their normal positions. Mirrors are to be used in order to facilitate process of 
application. Subjects will be instructed to not use the study drug in the vagina 
or in the rectum, and remove medication from any areas that experience 
stinging or burning immediately upon application. Site staff will also visually 
show the subjects what the correct amount of drug to be used per application 
looks like. 
The subject will also be trained on Subject Diary Card Completion and 
Contraception Methods. The subject will be given a study drug, mirror and a 
Subject Diary Card to capture application details, and acknowledge any 
changes in skin reactions, other AEs and concomitant medications during the 
intervening time between the site visits. 
On the following day after the Baseline visit (Day 1) the subject will apply the 
study drug on EAWs following the recommendations given during training at 
the clinic site. The treatment phase will consist of four weekly treatment cycles 
at a maximum, during which the drug will be applied twice a day (in the 
morning and at the bedtime) for 3 consecutive days, then discontinuing for 4 
consecutive days. Study drug will thus be applied only on Days 1, 2, 3, 8, 9, 
10, 15, 16, 17, 22, 23 and 24. 
Study visits will occur on the seventh (7) day of each treatment cycle: on Day 
7 (Week 1), Day 14 (Week 2), Day 21 (Week 3), and Day 28 (Week 4). Primary 
endpoint (total disappearance of all treated warts) will be evaluated during each 
of these visits. In case the primary endpoint is reached at any of the visits prior 
to the Day 28 visit, it will be considered as End of Study (EOS) visit – the 
Investigator will perform physical examination and repeat urine pregnancy test, 
and subject’s participation will be considered complete. If total disappearance 
of warts is not achieved, a new treatment cycle will be initiated for a maximum 
of four cycles in total for the subject. 
During each study visit, the Investigator will collect vital signs, evaluate EAWs 
for absence or present, capturing the count of EAWs, record Local Application 
Site Reactions and adverse events (AEs), assess Subject Diary Card completion 
and subject’s compliance with the study drug application, review concomitant 
medication and confirm that there were no prohibited therapies applied from 
the last visit.  
In the event the primary endpoint (total disappearance of all warts within all 


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treated areas) has been achieved prior to the Day 28 visit, this visit will be 
considered End of Study (EOS) visit. In case a subject discontinues 
prematurely, the Investigator will conduct an Early Termination (ET) visit, 
capturing the reason for discontinuation and performing assessments of EOS 
visit. 
Number of Subjects 
and Sites 
The planned overall sample size for this clinical trial is approximately 413 adult 
male and female subjects with external anogenital warts, who will be 
randomized at a 3:3:1 ratio (test: RLD: placebo) at about 16 clinical research 
centers in the United States, Russia and Ukraine. mITT and PP population size 
will be approximately 392 and 350 correspondingly. 
Eligibility Criteria 
Subjects who satisfy ALL the following inclusion and have NONE of the 
following exclusion criteria may be enrolled in the study: 
INCLUSION CRITERIA 
1. Willing and able to provide written informed consent prior to 
participating in this study. 
2. Male or female subjects, aged 18-65 inclusive, with a clinical diagnosis 
of external anogenital warts (i.e., perianal warts and/or external genital 
warts), including two or more distinct external genital warts, and wart 
area that is equal or less than 10 cm2.  Histological confirmation should 
be obtained if there is any doubt of the diagnosis. 
3. Females of childbearing potential may be enrolled if they practice a 
method of birth control with a reliability of at least 90%. 
4. Sexually active study participants must agree to abstain from sexual 
activity of any kind throughout the treatment period to prevent cross- 
and reinfection by HPV.  
5. Any female subject with childbearing potential has a negative urine 
pregnancy test at Baseline. 
6. Negative HIV test within 4 weeks before Baseline. 
EXCLUSION CRITERIA 
7. Female subjects who are pregnant or lactating or planning to become 
pregnant during the study period. 
8. Hypersensitivity or intolerance to Podofilox or any component of the 
formulation. 
9. History of previous unsuccessful treatment with any formulation of 
Podofilox. 
10. Wart area that is greater than 10 cm2. 
11. Patients with internal anogenital and mucous membrane warts, 
Bowenoid papulosis, squamous cell carcinoma, active herpes lesion, 
or other skin abnormalities of treatment area, such as eczema, or skin 
that had not healed following surgery (cryosurgery, laser ablation or 
similar). 
12. Primary or secondary immunodeficiency. 


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13. Known presence of diabetes type I or II. 
14. Local irritation in any treatment area that would interfere with 
treatment. 
15. Use within 4 weeks prior to baseline of any: 1) treatment for anogenital 
warts, 2) systemic corticosteroids, or 3) systemic immunosuppressive 
drug. 
16. Any medical or surgical condition in the judgment of the Investigator 
that may interfere with the assessment of efficacy or safety, or pose a 
risk to the subject. 
17. Patients known to abuse alcohol and/or drugs, or with a history of 
chronic alcohol or drug abuse that may result in protocol non-
compliance. 
18. Received another investigational drug, device or biologic within 90 
days prior to the start of Screening or has planned to participate in 
another clinical trial while enrolled in this study. 
19. Subjects who in the opinion of the investigator, are unlikely to be able 
to follow the restrictions of the protocol and complete the study 
20. Employee (or employee’s family member) of the research center or 
private practice, CRO or Sponsor, or subjects who have a conflict of 
interest.  
21. Subjects living (e.g., siblings, spouses, relatives, roommates) in the 
same household cannot be enrolled in the study at the same time. 
22. Previous enrollment in this study, current enrollment in this study at 
another participating site or current enrollment in another study (in 
parallel to this study) at another clinical research site. 
Withdrawal and Early 
Discontinuation 
Subjects whose condition worsens and require alternate or supplemental 
therapy for the treatment of external anogenital warts during the study should 
be discontinued, and the Early Termination visit must be performed. 
Prohibited 
Concomitant 
Medication 
Use of following therapies is prohibited during study participation:  
• 
Any other topical products applied to the treatment area(s). 
• 
Systemic corticosteroid or immunosuppressive drugs. 
• 
Antipruritic, including antihistamines, in the 24 hours prior to study 
visits. 
• 
Immunomodulators. 
• 
Immunostimulatory drugs. 
• 
Interferons. 
• 
Another Investigational Drug. 
Study Drug 
Study drug includes Test, Reference and Placebo drug products. The Sponsor 
will supply study drug as matching 3.5 g of clear gel in aluminum tubes with 
an applicator tip, labeled for a blinded study. 
• 
Test Drug: Podofilox Topical Gel 0.5% (Hyloris Developments SA) 


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• 
RLD: Condylox® Gel 0.5% (Allergan Pharmaceuticals) 
• 
Placebo: Vehicle of the test drug (Hyloris Developments SA) 
Storage temperature is 20-25°C (68-77°F). 
Duration of Patient 
Study Participation 
Up to 50 Days 
Study Endpoints 
PRIMARY 
• 
The primary endpoint is the proportion of subjects in the per protocol 
(PP) population with “treatment success” defined as “total 
disappearance of all warts within all treated areas”. 
SECONDARY (Safety Endpoints) 
• 
Local application site reactions scores (erythema, dryness, 
burning/stinging, erosion, edema, pain, itching and bleeding) in each 
group during the study drug application period. 
• 
Other adverse events including serious adverse events throughout the 
study participation. 
Statistical Analysis 
EFFICACY ANALYSIS 
The difference in the proportion of subjects in the test and reference treatment 
groups who achieve “treatment success” defined as “total disappearance of all 
warts within all treated areas” at four days (± 5 days) after the last day of the 
last cycle of treatment will be evaluated using a two-sided, continuity-corrected 
90% confidence interval. The therapeutic equivalence of the test and reference 
products will be established if the confidence bounds of the 90% confidence 
interval are contained within the limits of -0.20 to +0.20.  The results in the 
per-protocol (PP) population will be considered definitive for therapeutic 
equivalence with those in the modified Intent-To-Treat (mITT) population 
considered supportive. 
Superiority will be assessed through continuity-corrected Z-tests comparing 
each active treatment to placebo. If both the test and RLD success proportions 
are statistically significantly greater than the placebo proportion (p<0.05, two-
sided) then they will be considered superior to the placebo.  The results in the 
mITT population will be considered definitive for superiority with those in the 
PP population considered supportive. 
Subjects discontinuing due to “treatment failure”, defined as worsening of 
condition and requiring alternate or supplemental therapy for the treatment of 
external anogenital warts during the study, will be included in the PP 
population analysis as treatment failures, and provided with effective 


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treatment. Subjects discontinued prematurely from the study for any other 
reason (i.e., noncompliance, or withdrawal of consent, etc.) will be excluded 
from the PP population, but included in the mITT population, using Last 
Observation Carried Forward (LOCF). 
SAFETY ANALYSIS 
Safety data analysis will include local application site reaction scores 
(erythema, dryness, burning/stinging, erosion, edema, pain, itching and 
bleeding), reported adverse events, vital signs and concomitant medication 
assessments summarized by treatment group and time point of collection, when 
appropriate. 
Descriptive statistics (arithmetic mean, standard deviation (SD), coefficient of 
variation (CV), median, minimum, and maximum) will be calculated for 
quantitative safety data as well as for the difference from baseline, when 
appropriate. 
Adverse events will be coded using the most recent version of the Medical 
Dictionary of Regulatory Activities (MedDRA®) noted in the Statistical 
Analysis Plan. A subject AE listing by MedDRA® system organ class and by 
preferred term within system organ class, including verbatim term, dose level, 
severity, and relationship to treatment, will be provided. This listing will 
include all AEs and serious adverse events (SAEs). Adverse events will also 
be presented in summary tables. Concomitant medications will be listed by 
treatment and coded using the most recent version of the World Health 
Organization (WHO) Drug Dictionary. 
 


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PRINCIPAL CONTACTS 
CLINICAL PROTOCOL AND CONDUCT 
INQUIRIES 
Maurizio Passanisi 
Head of Medical Affairs 
Hyloris Developments SA 
email: maurizio.passanisi@hyloris.com 
Bâtiment GIGA EE1 
Avenue Hippocrate n° 5 
4000 Liège (Sart-Tilman) 
Belgium 
Phone: +32 483 62 00 59 
 
Laïdya Syne 
Clinical Project Manager 
Hyloris Developments SA 
email: laidya.syne@hyloris.com 
Bâtiment GIGA EE1 
Avenue Hippocrate n° 5 
4000 Liège (Sart-Tilman) 
Belgium 
Phone: +32 489 84 49 60 
 
Evgeny Cherepanov, MD, PhD 
Project Manager, Global 
Biorasi LLC 
email: echerepanov@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Phone: +1 (786) 614-5048 
 
Alexander Romanov 
Project Manager, Eastern Europe 
Biorasi LLC 
email: aromanov@biorasi.com 
105005 Akademika Tupoleva Emb., 15, block 2, 
suite #511 
Moscow, Russia 
Phone: +7 (916) 214-4591 
 
 


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CLINICAL SAFETY INQUIRIES 
Sergey Pavlenko, MD 
Medical Monitor 
Biorasi Safety and Pharmacovigilance 
email: spavlenko@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 888-1916 
REPORTING OF SERIOUS ADVERSE 
EVENTS (SAES), PROTOCOL 
DEVIATIONS AND PREGNANCIES 
Biorasi Safety and Pharmacovigilance 
email: safety@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 221-3531 


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1 BACKGROUND AND RATIONALE 
1.1 Background to the Disease 
External anogenital warts (EAWs), also known as Condylomata acuminate, or anogenital human 
papillomavirus (HPV) infection, is one of the most common sexually transmitted infection (STI), in 86% 
caused by HPV types 6 or 11.1 HPV types 16, 18, 31, 33, and 35 are also occasionally found in anogenital 
warts (usually as co-infections with HPV 6 or 11) and can be associated with foci of high-grade squamous 
intraepithelial lesions (HSIL), particularly in persons who have HIV infection. 
Diagnosis of anogenital warts is usually made by visual inspection and can be confirmed by biopsy, which 
is indicated if lesions are atypical (e.g., pigmented, indurated, affixed to underlying tissue, bleeding, or 
ulcerated lesions). Biopsy might also be indicated in the following circumstances, particularly if the patient 
is immunocompromised (including those infected with HIV): 1) the diagnosis is uncertain; 2) the lesions 
do not respond to standard therapy; or 3) the disease worsens during therapy. HPV testing is not 
recommended for anogenital wart diagnosis, because test results are not confirmatory and do not guide 
genital wart management. 
The aim of treatment is removal of the wart and amelioration of symptoms, if present. The appearance of 
warts also can result in significant psychosocial distress, and removal can relieve cosmetic concerns. In 
most patients, treatment results in resolution of the wart(s). If left untreated, anogenital warts can resolve 
spontaneously, remain unchanged, or increase in size or number. Because warts might spontaneously 
resolve within 1 year, an acceptable alternative for some persons is to forego treatment and wait for 
spontaneous resolution. Available therapies for anogenital warts might reduce, but probably do not 
eradicate, HPV infectivity. Whether the reduction in HPV viral deoxyribonucleic acid (DNA) resulting 
from treatment reduces future transmission remains unknown. 
Treatment of anogenital warts should be guided by wart size, number, and anatomic site; patient preference; 
cost of treatment; convenience; adverse effects; and provider experience. No definitive evidence suggests 
that any one recommended treatment is superior to another, and no single treatment is ideal for all patients 
or all warts. The use of locally developed and monitored treatment algorithms has been associated with 
improved clinical outcomes and should be encouraged. Because all available treatments have shortcomings, 
some clinicians employ combination therapy (e.g., provider-administered cryotherapy with patient-applied 
topical therapy between visits to the provider). However, limited data exist regarding the efficacy or risk 
for complications associated with combination therapy. Treatment regimens are classified as either patient-
applied or provider-administered modalities. Patient-applied modalities are preferred by some persons 
because they can be administered in the privacy of their home. To ensure that patient-applied modalities 
are effective, instructions should be provided to patients while in the clinic, and all anogenital warts should 
be accessible and identified during the clinic visit. Follow-up visits after several weeks of therapy enable 
providers to answer any questions about the use of the medication and address any side effects experienced; 
follow-up visits also facilitate the assessment of the response to treatment. Following treatment alternatives 
are recommended by Center of Disease Control (CDC) for clinical management of EAWs (Table 1). 
Table 1. Recommended Regimens for External Anogenital Warts (i.e., penis, groin, scrotum, 


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vulva, perineum, external anus, and perianal*) 
Patient-Applied 
Podofilox 0.5% solution or gel, OR  
Imiquimod 3.75% or 5% cream†, OR  
Sinecatechins 15% ointment† 
Provider-
Administered 
Cryotherapy with liquid nitrogen or cryoprobe, OR 
Surgical removal either by tangential scissor excision, tangential shave excision, curettage, 
laser, or electrosurgery, OR 
Trichloroacetic acid (TCA) or Bichloroacetic acid (BCA) 80%–90% solution 
* Many persons with external anal warts also have intra-anal warts. Thus, persons with external anal warts might 
benefit from an inspection of the anal canal by digital examination, standard anoscopy, or high-resolution 
anoscopy 
† Might weaken condoms and vaginal diaphragms 
Podofilox (podophyllotoxin) is a patient-applied antimitotic drug that causes wart necrosis. Podofilox 
solution (using a cotton swab) or Podofilox gel (using an applicator tip or a finger) should be applied to 
anogenital warts twice a day for 3 days, followed by 4 days of no therapy. This cycle can be repeated, as 
necessary, for up to four cycles. The total wart area treated should not exceed 10 cm2, and the total volume 
of Podofilox should be limited to 0.5 mg of the gel per day. Health-care provider should describe proper 
application technique and identify which warts should be treated. Mild to moderate pain or local irritation 
might develop after treatment. Podofilox is contraindicated in pregnancy.2 
Imiquimod is a patient-applied, topically active immune enhancer that stimulates production of interferon 
and other cytokines. Imiquimod 5% cream should be applied once at bedtime, three times a week for up to 
16 weeks.3 Similarly, Imiquimod 3.75% cream should be applied once at bedtime, but is applied every 
night.4 With either formulation, the treatment area should be washed with soap and water 6–10 hours after 
the application. Local inflammatory reactions, including redness, irritation, induration, ulceration/erosions, 
and vesicles might occur with the use of Imiquimod, and hypopigmentation has also been described.5 A 
small number of case reports demonstrate an association between treatment with Imiquimod cream and 
worsened inflammatory or autoimmune skin diseases (e.g., psoriasis, vitiligo, and lichenoid dermatoses).6–
8 Data from studies of human subjects are limited regarding use of Imiquimod in pregnancy, but animal 
data suggest that this therapy poses low risk.2 
Sinecatechins is a patient-applied, green-tea extract with an active product (catechins). Sinecatechins 15% 
ointment should be applied three times daily (0.5 cm strand of ointment to each wart) using a finger to 
ensure coverage with a thin layer of ointment until complete clearance of warts is achieved. This product 
should not be continued for longer than 16 weeks.9–11 The medication should not be washed off after use. 
Genital, anal, and oral sexual contact should be avoided while the ointment is on the skin. The most common 
side effects of Sinecatechins are erythema, pruritus/burning, pain, ulceration, edema, induration, and 


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vesicular rash. The medication is not recommended for persons with HIV infection, other 
immunocompromised conditions, or with genital herpes because the safety and efficacy of therapy has not 
been evaluated. The safety of Sinecatechins during pregnancy is unknown. 
Cryotherapy is a provider-applied therapy that destroys warts by thermal-induced cytolysis. Health-care 
providers must be trained on the proper use of this therapy because over- and under-treatment can result in 
complications or low efficacy. Pain during and after application of the liquid nitrogen, followed by necrosis 
and sometimes blistering, is common. Local anesthesia (topical or injected) might facilitate therapy if warts 
are present in many areas or if the area of warts is large. 
Surgical therapy has the advantage of eliminating most warts at a single visit, although recurrence can 
occur. Surgical removal requires substantial clinical training, additional equipment, and sometimes a longer 
office visit. After local anesthesia is applied, anogenital warts can be physically destroyed by electrocautery, 
in which case no additional hemostasis is required. Care must be taken to control the depth of electrocautery 
to prevent scarring. Alternatively, the warts can be removed either by tangential excision with a pair of fine 
scissors or a scalpel, by carbon dioxide (CO2) laser, or by curettage. Because most warts are exophytic, this 
procedure can be accomplished with a resulting wound that only extends into the upper dermis. Hemostasis 
can be achieved with an electrocautery unit or, in cases of very minor bleeding, a chemical styptic (e.g., an 
aluminum chloride solution). Suturing is neither required nor indicated in most cases. In patients with large 
or extensive warts, surgical therapy, including CO2 laser, might be most beneficial; such therapy might also 
be useful for intraurethral warts, particularly for those persons who have not responded to other treatments.  
Trichloroacetic acid (TCA) and Bichloroacetic acid (BCA) are provider-applied caustic agents that destroy 
warts by chemical coagulation of proteins. Although these preparations are widely used, they have not been 
investigated thoroughly. TCA solution has a low viscosity comparable with that of water and can spread 
rapidly and damage adjacent tissues if applied excessively. A small amount should be applied only to the 
warts and allowed to dry (i.e., develop white frost on tissue) before the patient sits or stands. If pain is 
intense or an excess amount of acid is applied, the area can be covered with sodium bicarbonate (i.e., baking 
soda), washed with liquid soap preparations, or be powdered with talc to neutralize the acid or remove 
unreacted acid. TCA/BCA treatment can be repeated weekly if necessary. 
 
 


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1.2 Background to the Study Drug 
Podofilox is an antimitotic drug which can be chemically synthesized or purified from the plant families 
Coniferae and Berberidaceae (e.g. species of Juniperus and Podophyllum).  
RLD Condylox® Gel 0.5% is formulated for topical administration and supplied in 3.5 g aluminum tubes 
with an applicator tip. Each gram of drug substance contains 5 mg of Podofilox in a buffered alcoholic gel 
containing alcohol, glycerin, lactic acid, hydroxypropyl cellulose, sodium lactate, and butylated 
hydroxytoluene. 
Podofilox Gel 0.5% must be applied to the warts surface with the applicator tip or finger. The Podofilox 
Gel 0.5% may cause skin irritation, and hence must not be applied to the unaffected skin areas. Treatment 
cycle consists of twice daily applications (morning and evening) for three consecutive days followed by a 
four day “rest” period. This one-week cycle may be repeated until there is no visible wart tissue or for a 
maximum of four cycles in total. Treatment should be limited to 10 cm2 or less of wart tissue and to no 
more than 0.5 g of the gel per day. 
1.2.1 Clinical Pharmacology 
1.2.1.1 
Mechanism of Action 
Treatment of anogenital warts with Podofilox results in necrosis of visible wart tissue. The exact 
mechanism of action is unknown. 
1.2.1.2 
Pharmacokinetics 
In systemic absorption study in 52 patients, topical application of 0.05 mL of an ethanolic solution 
containing 0.5% Podofilox to external genitalia did not result in detectable serum levels.12 Applications of 
0.1 to 1.5 mL resulted in peak serum levels of 1 to 17 ng/mL one to two hours after application. The 
elimination half-life ranged from 1.0 to 4.5 hours. The drug was not found to accumulate after multiple 
treatments.12 
1.2.2 Clinical Experience 
Following data is available for RLD Condylox® Gel 0.5% clinical trials.  
In the first multicenter clinical study in 326 patients with anogenital warts, Condylox® Gel 0.5% and its 
vehicle were applied in a double-blind fashion to comparable patient groups.13 Of the 260 patients with 
efficacy data, 176 were treated with Condylox® Gel 0.5%. Patients applied Condylox® Gel 0.5% twice 
daily for three consecutive days followed by a 4 day “rest” period. At the end of 4 weeks, 38.4% of the 
patients had complete clearing of the wart tissue when treated with Condylox® Gel 0.5%. 
In the second multicenter clinical trial in 108 evaluable patients with anogenital warts, Condylox® 
(podofilox) Topical Solution 0.5% was compared with Condylox® Gel 0.5% for efficacy. As in the first 
clinical trial, patients applied Condylox® Gel 0.5% twice daily for three consecutive days followed by a 
four day “rest” period. Similar clearance rates were observed. At the end of 4 weeks, 25.6% of the patients 
had complete clearing of the wart tissue when treated with Condylox® Gel 0.5%.14 


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1.2.3 Safety Profile 
In clinical trials with Condylox® Gel 0.5%, the following local adverse reactions were reported during 
the treatment of anogenital warts: 
Table 2. Local adverse reactions reported in Condylox® Gel 0.5% clinical trials 
Adverse Reaction 
Mild 
Moderate 
Severe 
Inflammation 
32.2% 
30.4% 
9.3% 
Burning 
37.1% 
25.9% 
11.5% 
Erosion 
27.0% 
20.8% 
8.9% 
Pain 
23.7% 
20.4% 
11.5% 
Itching 
32.2% 
16.0% 
7.8% 
Bleeding 
19.2% 
3.0% 
0.7% 
The severity of local adverse reactions was predominantly mild or moderate and did not increase during the 
treatment period. Severe reactions were most frequent within the first 2 weeks of treatment. 
Other local adverse reactions reported included stinging (7%), and erythema (5%); less commonly reported 
local adverse events included desquamation, scabbing, discoloration, tenderness, dryness, crusting, fissures, 
soreness, ulceration, swelling/edema, tingling, rash, and blisters. The most common systemic adverse event 
reported during the clinical studies was headache (7%).14 
Further details are provided in the Investigator’s Brochure [IB]15. 
1.3 Rationale of the Study  
As stated in Section 1.2.1.2, topical application of 0.05 mL of an ethanolic solution containing 0.5% 
Podofilox to external genitalia did not result in detectable serum levels. In these settings, a conventional 
pharmacokinetic human study to demonstrate that Hyloris Developments SA Podofilox Gel 0.5% is 
bioequivalent to the Reference Listed Drug [RLD] Condylox® Gel 0.5% is not appropriate. 
Hyloris Developments SA will initiate a clinical endpoint bioequivalence (BE) study for a Podofilox Gel 
0.5% formulation for the treatment of external anogenital warts in comparison to Condylox® Gel 0.5% that 
follows the study design and recommendations according to Office of Generic Drugs (OGD) of U.S. Food 
and Drug Administration (FDA) Draft Guidance for Podofilox recommendations.16 


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2 STUDY OBJECTIVES AND ENDPOINTS 
2.1 Study Objectives 
2.1.1 Primary Objective 
To compare the clinical efficacy among patients with anogenital warts when treated with Podofilox Topical 
Gel 0.5% versus Condylox® Gel 0.5% and placebo. 
2.1.2 Secondary Objective 
To demonstrate safety of Podofilox Topical Gel 0.5% compared to Condylox® Gel 0.5% and placebo 
assessed by the frequency and severity of adverse events, and application site reaction scores (erythema, 
dryness, burning/stinging, erosion, edema, pain, itching and bleeding). 
2.2 Study Endpoints 
2.2.1 Primary Endpoint 
The primary endpoint is the proportion of subjects in the per protocol (PP) population with “treatment 
success” defined as “total disappearance of all warts within all treated areas”. 
2.2.2 Secondary Endpoint (Safety Endpoints) 
Local application site reactions scores (erythema, dryness, burning/stinging, erosion, edema, pain, itching 
and bleeding) in each group during the study drug application period. 
Other adverse events including serious adverse events throughout the study participation. 


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3 INVESTIGATIONAL PLAN 
3.1 Study Design 
This is a multicenter, parallel group, randomized, double-blind, placebo-controlled, trial with clinical 
endpoint comparing Podofilox Topical Gel 0.5% to Condylox® Gel 0.5% and a matching placebo. The 
study will be conducted among adult male and female patients with external anogenital warts.  
All the study related procedures will be conducted only after written informed consent is obtained at the 
Screening visit, which will occur up to 14 days prior to the Baseline (Days -14 to -1). During the Screening 
visit, the Investigator will record subject’s demographics, medical history, review concomitant medication, 
identifying any prohibited therapies that subject receives.  
The Investigator will assess vital signs and perform physical examination identifying any clinically 
significant abnormalities that may prevent subject from participation in the study. Laboratory samples will 
be collected, including HIV, Hepatitis B&C, urine pregnancy tests (UPT) for women of childbearing 
potential and Syphilis (if required by applicable local regulations).  
The Investigator will confirm the diagnosis of External Anogenital Warts (EAW) and the absence of 
contraindications specified in the exclusion criterion 5 during the visual examination. The biopsy of skin 
lesions will be performed per the discretion of the Investigator for microscopic verification of the diagnosis 
of EAWs. 
Once the results of Screening assessments are obtained, suggesting that the subject is eligible for entering 
the study, the Baseline visit (Day 0) will take place. During this visit, the Investigator will identify any AEs 
that occurred from the last visit, review concomitant and prohibited therapies, perform vital signs and 
physical examination. Those subjects who qualify for entering the study will be randomized to one of the 
following arms in a ratio of 3:3:1: 
• 
Arm 1 (Test product): Subjects in this arm will receive test formulation of Podofilox 
Topical Gel 0.5% (Hyloris Developments SA) 
• 
Arm 2 (Reference Listed Drug [RLD]): Subjects in this arm will receive RLD 
Condylox® Gel 0.5% 
• 
Arm 3 (Placebo): Subjects in this arm will receive a matching vehicle 
Randomization and study drug kit number assignment will be performed using an Interactive Response 
System (IRT).  
EAWs will be inspected and the count will be captured in the source worksheet and electronic Case Report 
Form (eCRF). The Investigator will assess the baseline level of Local Application Site Reactions, recording 
the scores on the Local Application Site Reactions Scale. 
During the inspection, study physician (Principal Investigator (PI), or Sub-Investigator) will train the 
subject on proper application of the study drug using the demonstration tube (contains vehicle of the study 
drug) and applicator.  The subject will be trained to apply the study drug to the surface of the warts at a 
proper amount (not to exceed 0.5 g per day or 0.25 g per application), avoiding unaffected and wounded 
skin areas, and to let the gel dry completely before allowing the return of opposing skin surfaces to their 


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normal positions. Mirrors are to be used to facilitate the process of application. Subjects will be instructed 
to not use the study drug in the vagina or in the rectum, and remove medication from any areas that 
experience stinging or burning immediately upon application. A visual representation of this quantity will 
be showed to the subjects. 
The subject will also be trained on Subject Diary Card completion and contraception methods. The subject 
will be given a kit of study drug, mirror and a Subject Diary Card to capture application details, and 
acknowledge any changes in skin reactions, other AEs and concomitant medications during the intervening 
time between the site visits. 
On the following day after the Baseline visit (Day 1) the subject will apply the study drug on EAWs 
following the recommendations given at the training. The treatment phase will consist of four weekly 
treatment cycles at a maximum, during which the drug will be applied twice a day (in the morning and at 
the bedtime) for 3 consecutive days, then discontinuing for 4 consecutive days. Study drug will thus be 
applied only on Days 1, 2, 3, 8, 9, 10, 15, 16, 17, 22, 23 and 24.  
Study visits will occur on the seventh (7) day of each treatment cycle: on Day 7 (Week 1), Day 14 (Week 
2), Day 21 (Week 3), and Day 28 (Week 4). Primary endpoint (total disappearance of all warts within all 
treated areas) will be evaluated during each of these visits. In case the primary endpoint is reached at any 
of the visits following Baseline, it will be considered as End of Study (EOS) visit – the Investigator will 
perform physical examination and repeat urine pregnancy test, and subject’s participation will be 
considered completed. If reduction of warts is absent or incomplete, a new treatment cycle will be initiated 
for a maximum of four cycles in total for the subject. 
During each study visit, the Investigator will collect vital signs, evaluate EAWs for healing, capturing the 
count, record Local Application Site Reactions and adverse events (AEs), assess Subject Diary Card 
completion and subject’s compliance with the study drug application, review concomitant medication and 
confirm that there were no prohibited therapies applied from the last visit.  
In the event the primary endpoint (total disappearance of all warts within all treated areas) has been 
achieved, this visit will be considered End of Study (EOS) visit. In case a subject discontinues prematurely, 
the Investigator will conduct an Early Termination (ET) visit, capturing the reason for discontinuation and 
performing assessments of EOS visit. 
3.2 Number of Subjects and Sites  
The planned overall sample size for this clinical trial is approximately 413 adult male and female patients 
with external anogenital warts, who will be randomized at a 3:3:1 ratio (test: RLD: placebo) at about 16 
clinical sites in the United States, Russia and Ukraine. 


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4 SELECTION AND WITHDRAWAL OF STUDY POPULATION 
4.1 Eligibility Criteria 
Subjects who satisfy ALL of the following inclusion and have NONE of the following exclusion criteria 
may be enrolled in the study: 
4.1.1 Inclusion Criteria 
1. Willing and able to provide written informed consent prior to participating in this study. 
2. Male or female subjects, aged 18-65 inclusive, with a clinical diagnosis of external anogenital warts 
(i.e., perianal warts and/or external genital warts), including two or more distinct external genital 
warts, and wart area that is equal or less than 10 cm2. Histological confirmation should be obtained 
if there is any doubt of the diagnosis. 
3. Females of childbearing potential may be enrolled if they practice a method of birth control with a 
reliability of at least 90%. 
4. Sexually active study participants must agree to abstain from sexual activity of any kind throughout 
the treatment period to prevent cross- and reinfection by HPV.  
5. Any female subject with childbearing potential has a negative urine pregnancy test at Baseline. 
6. Negative HIV test within 4 weeks before Baseline. 
4.1.2 Exclusion Criteria 
1. Female subjects who are pregnant or lactating or planning to become pregnant during the study 
period. 
2. Hypersensitivity or intolerance to Podofilox or any component of the formulation. 
3. History of previous unsuccessful treatment with any formulation of Podofilox. 
4. Wart area that is greater than 10 cm2. 
5. Patients with internal anogenital and mucous membrane warts, Bowenoid papulosis, squamous cell 
carcinoma, active herpes lesion, or other skin abnormalities of treatment area, such as eczema, or 
skin that had not healed following surgery (cryosurgery, laser ablation or similar). 
6. Primary or secondary immunodeficiency. 
7. Patients with diabetes type I or II. 
8. Local irritation in any treatment area that would interfere with treatment. 
9. Use within 4 weeks prior to baseline of any: 1) treatment for anogenital warts, 2) systemic 
corticosteroids, or 3) systemic immunosuppressive drug. 
10. Any medical or surgical condition in the judgment of the Investigator that may interfere with the 
assessment of efficacy or safety, or pose a risk to the subject. 
11. Patients known to abuse alcohol and/or drugs, or with a history of chronic alcohol or drug abuse 
that may result in protocol non-compliance. 
12. Received another investigational drug, device, or biologic within 90 days prior to the start of 
Screening or has planned to participate in another clinical trial while enrolled in this study.  
13. Subjects who in the opinion of the investigator, are unlikely to be able to follow treatment 
instructions, protocol requirements and complete the study 
14. Employee (or employee’s family member) of the research center or private practice, CRO or 
Sponsor, or subjects who have a conflict of interest.  


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15. Subjects living (e.g., siblings, spouses, relatives, roommates) in the same household cannot be 
enrolled in the study at the same time. 
16. Previous enrollment in this study, current enrollment in this study at another participating site or 
current enrollment in another study (in parallel to this study) at another clinical research site. 
4.2 Withdrawal and Early Discontinuation 
A subject may voluntary withdraw from the study at any time and for any reason without prejudice to his 
or her future medical care. The Investigator, Sponsor, or Medical Monitor may also withdraw the subject 
at any time if it is medically necessary or in the interest of subject safety. Additional reasons for premature 
discontinuation of study drug may include adverse events and major non-compliance with study procedures 
as described below. The withdrawal of a patient from study drug by the Investigator should be discussed 
with the Medical Monitor before the patient stops study drug, whenever possible. 
A subject will be discontinued from this study if any of the following criteria are met: 
• 
Withdrawal of consent by the subject is received. 
• 
In the opinion of the Investigator, it is not in the subject’s best interests to continue in the study. 
• 
Occurrence of an Adverse Event (AE) or Serious Adverse Event (SAE), which, in the opinion of 
the Investigator, warrants discontinuation of the subject from the study. 
• 
Pregnancy (refer to Section 7.6). 
• 
Significant non-compliance with study procedures that would interfere with the study results or 
increase the subject’s risks in the study.  
• 
If subject is deemed to be a treatment failure, which is defined as worsening of condition 
(increase in the number of warts, in the size of the warts, or other clinical signs as determined by 
the Investigator) and requiring alternate or supplemental therapy for the treatment of external 
anogenital warts during the study.  
• 
The subject’s medication code is unblinded. 
• 
Subject did not meet, or no longer meets, the entry criteria. 
• 
The subject is lost to follow-up.  The investigator will document efforts to attempt to reach the 
subject twice by telephone and will send a certified follow-up letter before considering that 
subject lost to follow-up. All attempts must be thoroughly recorded. 
• 
Investigator discretion. 
Subjects discontinuing due to “treatment failure” will be included in the PP population analysis as treatment 
failures, and will have alternative treatment recommended by the Investigator. Subjects discontinued 
prematurely from the study for any other reason (i.e., noncompliance, or withdrawal of consent, etc.) will 
be excluded from the PP population, but included in the ITT population, using Last Observation Carried 
Forward (LOCF). 
In the case if subject discontinues prematurely, the Investigator will perform Early Termination (ET) visit, 
capturing the reason for discontinuation and performing assessments of EOS visit (Section 6.3.4). 
If a subject does not return for a scheduled visit, every effort will be made to contact the subject and 
document the End of Study (EOS) visit assessments. The patient should at least be contacted twice by phone 
and, if no answer, by registered letter within a week. The Investigator must document the primary reason 


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for discontinuation of a study subject in the source document and on the appropriate electronic case report 
form (eCRF). 
Randomized subjects who discontinue due to an adverse event will have all events documented and 
followed to satisfactory resolution, as detailed in Section 7.4. 
After a subject has been discontinued, he/she will not be allowed to re-enroll in the study at any facility. 
4.3 Contraception and Pregnancy Avoidance Measures 
The study will require that all female subjects of childbearing potential practice a method of birth control 
with a reliability of at least 90% defined as follows: 
 
Female subjects must be surgically sterile, postmenopausal (for at least one year). 
 
Female subjects not surgically sterile or postmenopausal (for at least one year), and non-
vasectomized male subjects, must practice at least one of the following methods of birth control: 
o Total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to 
Screening visit, throughout the study). 
o A vasectomized partner. 
o Hormonal contraceptives (oral, parenteral, or transdermal) for at least three months prior 
to study drug administration or intrauterine contraception/device double-barrier method 
(such as male condom, female condom, diaphragm, sponge, or cervical cap together with 
spermicidal foam/gel/film/suppository). 
Sexually active study participants must agree to abstain from sexual activity of any kind throughout the 
treatment period to prevent cross- and reinfection by HPV. 
If a subject becomes pregnant during the participation in the study, the Investigator will immediately 
discontinue the patient from the study and contact the Medical Monitor, Biorasi Safety Team, or Sponsor. 
Diligent efforts will be made to determine the outcome for all pregnancy exposures in the clinical trial. 
Information on the status of the mother and the child will be forwarded to the Biorasi Safety Team using 
the Pregnancy Data Collection Form. Generally, follow-up will occur within 6 to 8 weeks following the 
estimated delivery date. Any premature termination of the pregnancy will be reported.  


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5 STUDY DRUG ADMINISTRATION 
5.1 Identity of Study Drug(s) 
The term study drug is used to refer to the Test, Reference and Placebo drug products. 
5.1.1 Formulation of Study Drug 
Study drug in this study will be supplied as matching 3.5 g of clear gel in aluminum tubes with an applicator 
tip, labeled for a blinded study. 
• 
Test Drug: Podofilox Topical Gel 0.5%, manufactured for Hyloris Developments SA by Perrigo 
Company Ltd. 
• 
RLD: Condylox® Gel 0.5%, manufactured for Allergan Pharmaceuticals, by DPT Laboratories, 
Ltd., distributed by Actavis Pharma, Inc. 
• 
Placebo: Vehicle of the test drug, manufactured for Hyloris Developments SA by Perrigo 
Company Ltd. 
5.2 Packaging and Labeling 
The study drug tubes to be dispensed to the subject will be packaged and labeled in accordance with Good 
Manufacturing Practice. Each individual tube of the study drug will be diaper-labelled and look identical.  
5.3 Storage of the Study Drug 
Storage temperature for study drug is 20-25°C (68-77°F). All study medication supplies must be kept in a 
secure cabinet or room. Only the designated study personnel will have access to study medication supplies. 
The Investigator will maintain temperature continued monitoring of the study drug with temperature 
readings. All temperature excursions must be reported to Biorasi using Temperature Excursion Form. The 
study drug that experienced excursions must be quarantined until the Medical Monitor / Sponsor’s approval 
on future use. 
5.4 Reserve Sample Retention 
When a site receives a shipment of the study drug, study pharmacist, or designated study personnel will 
separate one randomly selected set of study drug for retention. The retention samples will be marked 
accordingly, stored securely along with sealed randomization codes for FDA use (according to Guidance 
for Industry - Handling and Retention of BA and BE Testing Samples.; 2004, and CRF 320.38 and 320.63). 
For all subsequent shipments, the same procedure is to be followed.17 Retention samples will be stored 
under the same temperature conditions as the study drug for use in the study by subjects. 
The Investigator will store the retention samples of the study drug until such time or until notification is 
received from the Sponsor that the samples are no longer required and proper instruction of what to do with 
the sample is given by the Sponsor. 


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5.5 Treatment Assignment (Randomization) 
Randomization will be performed using an Interactive Response Technology (IRT) system that is fully 
integrated with the Electronic Data Collection (EDC) system. Randomization and treatment assignment 
will be determined at the time the subject has met all eligibility criteria and is ready for enrollment. Subjects 
will be randomized in a 3:3:1 ratio to receive the test product, RLD, or placebo. 
Subjects will be stratified by gender. A balanced distribution amongst male and female subjects across the 
study in all three study groups will be maintained by the IRT system which will assign subjects to the 
treatment arm and specify the kit number to be dispensed.  
The randomization scheme will be held by the independent third party throughout the conduct of the study 
(through database lock) and will not be available to the Hyloris Developments SA, Biorasi, Investigator, or 
study staff, or to clinical staff who could have an impact on the outcome of the study. 
5.6 Blinding 
This is a double-blind study, thus Sponsor, Biorasi, Investigator, site staff, study monitors, and subjects will 
be blinded to the randomization scheme. The packaging of the test, RLD products and placebo will be 
similar in appearance to make no difference in treatment to the subjects and study staff.  
The blinding code must not be broken except in emergency situations for which the identification of the 
study treatment of a subject is required by the Investigator to complete a serious adverse event report. In 
such situations, the Medical Monitor or the Investigator will use the IRT system to unblind the treatment 
for the individual subject. Unblinded information will be held by designated individual(s), and the date and 
reason for breaking the blind must be recorded.  
As the study is blinded, the Investigator should promptly document and report to the Sponsor any premature 
unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational 
product(s). 
5.7 Treatment Administration 
5.7.1 Study Drug Dispensation and Application 
Subjects will receive the randomized treatment along at the Baseline Visit (Day 0) with a Subject Diary 
Card, written instructions and precautions. Prior to dispensation Investigator will measure the weight of the 
study medication using electronic scales. Each subject will be instructed by the Investigator on proper 
application technique. The Investigator will identify which warts should be treated during the application 
training session at the Baseline visit.  
Following application instructions will be provided to the subject: 
1. This medication is for topical use only. Apply it on the warts pointed out by your doctor. It should 
be applied once in the morning and again in the evening (at bedtime) for 3 days followed by a 4-
day rest period. If the warts do not go away, your study doctor will decide if another cycle of 


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treatment is necessary.  This cycle may be repeated up to 4 times. If the warts do not go away after 
4 weeks of treatment, your study doctor will advise you on the alternative treatment methods. 
2. To apply the study drug, use an applicator tip or your finger. Apply a small amount of medication 
to the wart to cover it. Application on the surrounding normal tissue should be minimized.  If the 
genital wart is in a skin fold, spread the skin apart and apply the medicine. Allow the treated skin 
to dry before releasing the skin fold. Wash your hands thoroughly with soap and water before and 
after each application. 
3. This medication should be used only as directed by study doctor. You should wash your hands 
thoroughly before and after each application. It is for external use only. Avoid contact with the 
eyes. If contact occurs, immediately wash with plenty of water and contact your study doctor. 
4. Do NOT use large amounts. Maximum amount that can be applied is 0.5 gram per day (or 0.25 
gram per one application). Do NOT apply more often or use for a longer period than directed. Your 
condition will not clear faster, and the chance for side effects may be increased. 
5. Do NOT use this medication for any disorder other than for External Anogenital Warts.  The 
medication should NOT be used in the vagina or in the rectum or on any open wounds.  You should 
not wash the medication off the wart area unless you experience excessive pain, burning, or itching.   
6. Report any signs of adverse reactions to your study doctor. If the area you are putting study 
medication on is bleeding or swollen, or if there is excessive pain, burning or itching, stop applying 
it and contact your doctor. 
7. Do not have sexual contact of any kind during the treatment period. 
8. The study drug is flammable and must be kept away from open flames. 
The subject will return used tubes of the study drug at the next visit along with completed Subject Diary 
Card. The Investigator will measure the weight of returned study medication using electronic scales. 
Measured weight of the study medication will be documented in a Study Drug Accountability Log. 
If an additional treatment cycle is required, the Investigator will dispense the returned tube. If the remaining 
amount of the study drug in the used tube is not sufficient for another treatment cycle, study site will 
dispense a new tube of the study drug using the IRT system. The Investigator will measure the weight of 
study medication using electronic scales prior to providing to subject. 
5.8 Treatment Compliance 
Treatment compliance will be assessed by the Investigator based on Subject Diary Card completion at each 
study visit following the Baseline. Compliant subjects are defined as those who have completed at least 
75% and no more than 125% of study drug applications until treatment success or for a maximum of four 
cycles of treatment. 
5.9 Accountability, Destruction and Return of Study Supplies 
The Sponsor will supply sufficient quantities of the study drug for the following: 
1. Completion of this study  
2. Samples retention, as per applicable regulations described in Section 5.4. 
The study pharmacist or designated study personnel will maintain a Study Drug Accountability Log 
itemizing all study drug received, dispensed to and returned from each subject during the study. All 


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dispensed tubes must be accounted for, and any discrepancies explained. Study site should contact site 
Clinical Research Associate (CRA) in the case if any dispensing errors or discrepancies are discovered. 
Prior to site closure and at appropriate intervals during the study, site CRA will perform study drug 
accountability and reconciliation. At the end of the study, the Investigator will retain all the original 
documentation regarding study drug accountability, return, and/or destruction, and copies will be sent to 
the Biorasi/Sponsor. 
 All unused and used Study Drug tubes will be returned to the Sponsor or its designee for destruction at the 
end of the study except for the Retention Samples. 
5.10 Prior, Concomitant and Prohibited Therapy  
Current medications and any medications taken within the 30 days prior to the start of the study will be 
recorded as prior/concomitant medications (using their generic name, if known) with the corresponding 
indication, start and stop dates. The medications to be recorded include prescription and all over-the-counter 
(OTC) medications and all dietary supplements. All medications taken on a regular basis, including aspirin 
and acetaminophen, should be recorded prior to commencing the use of the investigational product. Any 
medications started during the study (including “as needed” medications) will be recorded in the 
concomitant medication list as soon as the Investigational Site will become aware of the medication being 
added. 
Prohibited Therapies are those medicinal products and treatment methods that are not allowed in the 
current study within the timeframes specified in the Table 3. 
Table 3. List of Prohibited Medication and Treatment Methods 
Treatment 
Timeframe the Therapy is Prohibited 
Systemic corticosteroid or immunosuppressive drugs 
4 weeks prior to the Baseline visit and until the 
EOS/ET visit 
Treatment of EAWs, including surgical removal 
(cryosurgery, 
laser 
ablation, 
electrocoagulation, 
shaving, etc.), over-the-counter (OTC) treatments, 
Trichloroacetic acid (TCA) or bichloroacetic acid 
(BCA) solution, etc. 
Any other topical products applied to the treatment 
area(s) 
From the Baseline visit and until the EOS/ET visit 
Antipruritic 
(anti-itch 
medication), 
including 
antihistamines 
within 24 hours of study visits 
Immunomodulators 
From the Baseline visit and until the EOS/ET visit 
Immunostimulatory drugs 
From the Baseline visit and until the EOS/ET visit 
Interferon 
From the Baseline visit and until the EOS/ET visit 
Another Investigational Drug 
90 days prior to the Screening visit and until the EOS/ET 
visit 
If the Investigator becomes aware of a subject having taken a prohibited medication, they will report the 
incident to the Medical Monitor and Biorasi within 24 hours, and the Medical Monitor and/or Sponsor will 
provide written approval of the subject’s continuation or discontinuation from the study. 


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6 STUDY PROCEDURES AND SCHEDULE OF ACTIVITIES 
The following sections describe the procedures to be completed during the study. Subjects are to be assessed 
by the same Investigator or site personnel whenever possible. 
6.1 Administrative Procedures  
6.1.1 Subject Informed Consent 
A signed and dated, study-specific, approved by Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC) and applicable regulatory authorities Informed Consent Form must be obtained from each 
subject prior to performing any study related procedures. No study related procedures or activities may be 
performed until each subject is fully informed and the consent form is signed and dated. 
A copy of the signed consent (or a second original) will be given to every participant (or legally authorized 
representative) and the original will be maintained with the participant’s records.   
Subjects that require a wash-out of more than 30 days from their initial informed consent/ signing must be 
re-consented before any further study procedures can begin. 
6.1.2 Documentation of Screen Failures 
Investigators must account for all subjects who sign informed consent and will maintain an Enrollment log 
capturing subjects screened and indicating who was enrolled or excluded and the reason why. If the subject 
is found not to be eligible prior to enrollment, the reason(s) for ineligibility must be documented by the 
Investigator. 
Subject Numbers assigned to subjects who fail Screening will not be re-used.   
6.2 Study Procedures and Evaluations 
6.2.1 Clinical Evaluations 
The following clinical evaluations will be conducted during the study: 
6.2.1.1 
Subject Demographics 
Basic demographic information, including date of birth, sex, ethnicity, and race will be recorded at the 
Screening visit. 
6.2.1.2 
Medical history 
Medical history will be collected at the Screening visit. Relevant medical history, including any history of 
HPV infections and EAWs will be documented. Presence of immunodeficiency, or other clinically 
significant ongoing medical condition or disease will disqualify subject from participation. 


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6.2.1.3 
Concomitant Medication Recording 
All medications (both prescription and nonprescription, and including vitamins, herbals, topicals, inhaled, 
and intranasal) taken within 30 days prior to the start of the Study Treatment and through the final study 
visit will be recorded on the appropriate eCRF (using their generic and brand name, if known) with the 
corresponding indication, start and stop dates. At each study visit, subjects will be asked whether they have 
started or discontinued any medication since their previous study visit. This includes single use or PRN 
(pro re nata, as needed) medication use. 
Previous treatment of HPV infection with any formulation of Podofilox must be recorded irrespectively of 
the term it was given. Corresponding condition shall be captured in the subject’s Medical History. 
6.2.1.4 
Vital Signs 
Vital signs will be collected at each study visit. Vital signs will include body temperature, pulse rate and 
blood pressure (systolic and diastolic). Blood pressure and pulse rate will be measured after the subject has 
been sitting restfully for at least 5 minutes. 
Any abnormal characteristics will be evaluated by the Investigator from based on their significance. 
Abnormal vital signs will be considered AEs if they require therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs due to the clinical judgement. 
6.2.1.5 
Physical examination 
Physical examination, including height, weight, and evaluation of organs and systems (General 
Appearance, Heart/Cardiovascular, Lungs, Gastrointestinal, Ears / Nose / Throat, Extremities, and Skin) 
will be assessed at the Screening, Baseline and EOS/ET visits. 
Clinically significant abnormalities other than presence of external anogenital warts will disqualify subject 
from participation. The following skin abnormalities are also considered disqualifying:  
• 
Internal genital warts 
• 
Mucous membrane warts 
• 
Bowenoid papulosis 
• 
Squamous cell carcinoma 
• 
Active Herpes lesion within any treatment area 
• 
Eczema 
• 
Skin that had not healed following surgical procedure (cryosurgery, laser ablation, or similar). 
6.2.1.6 
Visual Examination of External Anogenital Warts 
Visual examination at the Screening visit aims to confirm the clinical diagnosis of external anogenital warts 
based on positive identification of perianal warts and/or external genital warts. Two or more distinct 
external genital warts, and wart area that is equal to or less than 10 cm2 are required for participation in the 
trial (refer to Section 4.1.1). 
Histological confirmation should be obtained at the discretion of the PI if there is any doubt of the diagnosis 
and to rule-out skin lesions of different origin, such as mucous membrane wart, Bowenoid papulosis, 
Squamous cell carcinoma, or active Herpes lesions. 


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The Investigator will record total number of anogenital warts within treatment area(s), indicating:  
(a) total number of external genital warts and  
(b) perianal warts at each study visit.  
A cluster of warts is to be counted as a single wart. As far as possible, the same physician will perform the 
record for the same subject throughout the study.  
Visual examination of EAWs will be repeated at each study visit. Total disappearance of all warts within 
all treated areas will be considered a “treatment success”. 
6.2.1.7 
Assessment of Local Application Site Reactions 
Local skin reaction scores for erythema, dryness, burning/stinging, erosion, edema, pain, itching and 
bleeding will be recorded by the Investigator for every study visit based on their intensity. 
Table 4. Skin Reaction Scale 
Reaction 
Score, 0-3* 
erythema 
 
dryness 
 
burning/stinging  
erosion 
 
edema 
 
pain 
 
itching 
 
bleeding 
 
* Scores are: 0=absent, 1=mild (slight, barely perceptible), 2=moderate (distinct presence), 3=severe 
(marked, intense) 
 
The Application Site Reaction Assessment must be conducted by qualified investigators listed on the Form 
FDA 1572 who have been delegated these tasks by the PI. The PI may delegate this task to Physicians, 
Physician Assistants, or Nurse Practitioners, Registered Nurses (RNs) or Licensed Practical Nurses (LPNs) 
who have documented training and past experience conducting this assessment. 
Application site reactions (erythema, dryness, burning/stinging, erosion, edema, pain, itching, and bleeding) 
are to be recorded as adverse events of special interest. 
All application site reactions must be recorded as adverse events in the source document and eCRFs. 
 
 
 
6.2.1.8 
Adverse Event Assessments 
Beginning with the Screening visit and through the EOS/ET visit, the Investigator and study personnel will 


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review each subject’s clinical evaluation findings and query the subject directly regarding AEs (see Section 
7, Safety Data Collection, Recording and Reporting). Subjects must be followed for AEs until the final 
required protocol visit or until all drug-related toxicities and SAEs have resolved (or are considered 
chronic/stable), whichever is later. 
6.2.2 Laboratory Evaluations 
The following laboratory evaluations will be conducted during the study: 
6.2.2.1 
Serology test for HIV 
During the Screening visit (Visit 1), the Investigator or designee will obtain serum test for HIV. Negative 
test is required to participate in the study. 
6.2.2.2 
Test for Hepatitis B&C 
During the Screening visit (Visit 1), the Investigator or designee will obtain serum test for Hepatitis B&C. 
Negative test is required to participate in the study. 
6.2.2.3 
Pregnancy test 
A urine pregnancy test will be performed at the Screening, Baseline and EOS/ET visits for females of 
childbearing potential (refer to Section 4.2 for definitions). The Baseline urine pregnancy test result must 
be available and must be negative before the subject applies the first application of study drug. An 
investigator may repeat the pregnancy test anytime during the study if there is any suspicion or possibility 
that the subject may be pregnant. 
6.2.2.4 
Test for Syphilis 
The test for Syphilis will be performed if required by applicable local regulations. During the Screening 
visit (Visit 1), the Investigator or designee will obtain serum test for Syphilis. Negative test is required to 
participate in the study. 
6.2.3 Subject Diary Card Review 
The subject will be given a kit of study drug, mirror and a Subject Diary Card to capture application details, 
and acknowledge any changes in skin reactions, other AEs and concomitant medications during the 
intervening time between the site visits. Subjects will fill out their diary cards during each treatment cycle 
noting the following: 
• 
Time and date of application 
• 
Any changes in skin reactions, other AEs and concomitant medication 
Subjects will return their completed diary cards to the clinical site at each of the post-baseline visits (visits 
3-5 and EOS/ET) for review and filing with the subject’s source documents. The Investigator will verify 
that the subject complied with the application requirements. The study staff will sign off on completed diary 
card. Any missed application notations will be clarified with the subject and documented. Refer to Section 
5.8 for additional information regarding the treatment compliance. 


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6.3 Study Procedures 
6.3.1 Visit 1: Screening (Day -14 up to -1) 
Screening visit will occur at up to 14 days prior to the Baseline. During the screening, the following 
procedures will be performed: 
• 
Informed Consent 
• 
Collection of Subject Demographics and Medical History 
• 
Concomitant and Prohibited Therapies Review 
• 
Assessment of Vital Signs 
• 
Physical Examination 
• 
Serology test for HIV, Hepatitis B and C 
• 
Urine pregnancy test 
• 
Test for Syphilis (if required) 
• 
Confirmation and documentation of the diagnosis of anogenital warts during the visual inspection 
(histological confirmation will be obtained if there is any doubt of the diagnosis) 
• 
Eligibility Criteria Check 
• 
Adverse Events Assessment 
• 
Schedule next visit to occur within window 
6.3.2 Visit 2: Baseline Visit (Day 0) 
• 
Adverse Events Assessment 
• 
Concomitant and Prohibited Therapies Review  
• 
Assessment of Vital Signs 
• 
Physical Examination 
• 
Urine Pregnancy Test 
• 
Visual Inspection of EAWs 
• 
Assessment of Local Application Site Reactions  
• 
Eligibility Criteria Check 
• 
Randomization 
• 
Study Drug Dispensation 
• 
Subject Diary Card Dispensation 
• 
Training on Study Drug Application 
• 
Training on Subject Diary Card completion and contraception methods 
• 
Schedule next visit to occur within window 
6.3.3 Visits 3-6 (Day 7 [Week 1], Day 14 [Week 2], Day 21 [Week 3], and 
Day 28 [Week 4]) 
The following procedures will be performed: 
• 
Subject Diary Card Return, Review and Dispensation 
• 
Adverse Events Assessment 
• 
Concomitant and Prohibited Therapies Review  
• 
Assessment of Vital Signs 


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• 
Assessment of Local Application Site Reactions  
• 
Visual Inspection of EAWs. In the case there is a total disappearance of all warts within all treated 
areas at visits 2, 3, 4, or 5, this visit will be considered an End of Study (EOS) visit. In the case 
where reduction of warts is absent or incomplete, a new treatment cycle will be initiated for a 
maximum of four cycles in total for the subject. 
• 
Study Drug Return and Accountability 
• 
Study Drug Dispensation 
6.3.4 End of Study / Early Termination (EOS/ET) visit 
The visit at which “treatment success” has been achieved will be considered EOS visit.  
If “treatment success” has not been achieved through the EOS/ET visit (Day 28±5 [Week 4]), then the 
subject will be considered “treatment failure” and EOS activities will be performed. Similarly, if the 
Investigator assesses the subject’s condition at any time and determines that the subject’s condition has 
worsened to the degree that it is unsafe for the subject to continue in the study, the subject may be 
discontinued from the study as “treatment failure”. ET visit procedures will be performed, and an alternative 
treatment will be advised at the Investigator’s discretion. 
Subjects discontinuing from the study sooner than the Day 28 visit will undergo the ET visit as soon as 
possible.  
Following activities will be performed at EOS/ET visit: 
• 
Subject Diary Card Return and Review 
• 
Adverse Events Assessment 
• 
Concomitant and Prohibited Therapies Review  
• 
Assessment of Vital Signs 
• 
Physical Examination 
• 
Assessment of Local Application Site Reactions  
• 
Visual Inspection of EAWs 
• 
Study Drug Return and Accountability 
• 
Urine Pregnancy Test 
• 
For prematurely discontinuing subjects - record reason for discontinuation. 
6.3.5 Unscheduled Visit 
Subjects will be encouraged to report any complications or adverse effects during their participation. 
Investigator may evaluate the subject at an unscheduled visit, if subject’s condition will be considered as 
worsening. If the investigator assesses the subject’s condition and determines that the subject’s condition 
has worsened to the degree that it is unsafe for the subject to continue in the study, the subject may be 
discontinued from the study as a treatment failure, an Early Termination Visit conducted, and a standard of 
care treatment may be advised at the investigator’s discretion. The following procedures should be 
performed at the Unscheduled Visit if required. 
• 
Subject Diary Card Return, Review and Dispensation 
• 
Adverse Events assessment 


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• 
Concomitant and Prohibited Therapies review  
• 
Collection of Vital Signs 
• 
Physical examination 
• 
Assessment of Local Application Site Reactions  
• 
Visual Inspection of EAWs 


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7 SAFETY DATA COLLECTION, RECORDING AND REPORTING 
The Investigator will monitor each subject for clinical evidence of adverse events on a routine basis 
throughout the study. The Investigator will assess and record any AE in detail including the date of onset, 
description, severity, time course, duration and outcome, relationship of the adverse event to study drug, an 
alternate etiology for events not considered “related” or “probably related” to study drug, final diagnosis, 
if known, and any action(s) taken. For AEs to be considered intermittent, the events must be of similar 
nature and severity and each intermittent AE will be reported separately. AEs and SAEs, whether in 
response to a query, observed by site personnel, or reported spontaneously by the subject will be recorded, 
monitored and followed-up until the resolution (or until the Investigator deems the event to be 
stable/chronic). 
7.1 Definitions 
7.1.1 Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, 
whether the event is considered causally related to the use of the investigational product. 
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
accidental or intentional overdose, drug abuse, or drug withdrawal. Any worsening of a pre-existing 
condition or illness is considered an AE. Clinically significant abnormalities are to be followed to resolution 
(i.e. become stable, return to normal, return to Baseline, or become explainable). Laboratory abnormalities 
and changes in vital signs are considered AEs only if they necessitate therapeutic medical intervention, 
and/or if the Investigator considers them to be AEs. 
7.1.2 Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to the Biorasi Safety and Pharmacovigilance 
as a serious adverse event (SAE) using SAE report form within 24 hours of occurrence or notification to 
the study site: 
Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, would have resulted in immediate 
fatality if medical intervention had not been taken. This does not include an event 
that would have been fatal if it had occurred in a more severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of time. This does 
not include an emergency room visit or admission to an out-patient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs the 
subject's hospital stay. 
Congenital 
An anomaly detected at or after birth or any anomaly that result in fetal loss. 


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Anomaly/birth defect 
Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the activities of 
daily living of a study subject. Disability is not intended to include experiences of 
relatively minor medical significance such as headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle). 
Other Important Medical 
Event 
An important medical event that may not be immediately life-threatening or result in 
death or hospitalization, but based on medical judgment may jeopardize the subject 
and may require medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life- threatening, hospitalization, prolongation of 
hospitalization, congenital anomaly, or persistent or significant 
disability/incapacity). Examples of such events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
7.2 Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE and SAE: 
Mild 
The event is transient and easily tolerated by the subject. 
Moderate 
The event causes the subject discomfort and interrupts the subject's usual activities. 
Severe 
The event causes considerable interference with the subject's usual activities and may 
be incapacitating or life-threatening. 
7.3 Causality of Adverse Events 
The Investigator will use the following definitions to assess the relationship of the AE/SAE to the use of 
investigational product: 
Related 
The event occurred within a reasonable time after drug administration or drug 
concentration and body fluids demonstrated that the study drug was present: the event 
could not be reasonably explained by known characteristics including concomitant 
therapies; the adverse event abated after discontinuing the study drug. 
Probably Related 
The event has a strong temporal relationship to study drug or recurs on re-challenge and 
another etiology is unlikely or significantly less likely. 
Possibly Related 
The event has a strong temporal relationship to the study drug and an alternative 
etiology is equally or less likely compared to the potential relationship to study drug. 
Probably Not Related 
The event has little or no temporal relationship to the study drug and/or a more likely 
alternative etiology exists. 
Not Related 
The event is due to an underlying or concurrent illness or effect of another drug and is 
not related to the study drug (e.g., has no temporal relationship to study drug or has a 
much more likely alternative etiology). 
If an Investigator's opinion of possibly, probably not, or not related to study drug is given, an alternate 
etiology must be provided by the Investigator for the AE. 


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7.4 Adverse Event Collection Period 
Any AE/SAE prior to the Screening visit will be considered past medical history (PMH). The AE reporting 
period for this study begins with the signature of the Informed Consent Form and, for unresolved AEs, ends 
30 days following the last study medication application. Those events that occur during the screening period 
and up to the day of the first application of the study drug will be considered Non-Treatment Emergent 
AEs. 
Adverse events that occur during the treatment period (starting from the day of the first application of Study 
Drug and up to the final protocol required visit) will be considered Treatment Emergent AEs (TEAEs).  
SAE(s) that are observed or spontaneously reported during the subject’s participation in the trial will be 
captured and monitored until the Investigator deems the event to be chronic or not clinically significant or 
the subject to be stable.  
 
7.5 Adverse Event Reporting 
Information regarding AEs will be derived by questioning the participants in an unbiased, general query 
(e.g., "How do you feel?” or “How have you been feeling since your last clinic visit?”), by subjects' 
spontaneous reports, or by observation.  
AEs will be recorded in the source documents. All AEs will then be transcribed into the CRF.  
For each sign, symptom or adverse event, the following information will be recorded in the CRF: 
• a brief descriptor of the adverse event 
• severity (mild/ moderate/ severe) 
• whether the AE was “serious” or not (as defined in the serious adverse event section) 
• frequency (single occurrence/ intermittent/ continuous) 
• outcome (resolved/ resolved with sequelae/ improving/still present and unchanging/ death 
• whether any treatment was administered for the AE. 
In the event of a SAE, whether related to study drug or not, the Investigator or representative must make 
an accurate and adequate report consisting of at least the minimum criteria (Site and Subject ID, Date site 
became aware of the event, SAE Term, Seriousness criteria, Study Drug information, Investigator/Reporter 
and site address) within 24 hours after the site became aware by email, fax, or telephone to Biorasi Safety 
and Pharmacovigilance team. Biorasi Safety and Pharmacovigilance team will complete the SAE report 
onto a MedWatch 3500A form for evaluation and convey for review by the Medical Monitor and Sponsor 
contact. Accurate Completion of the MedWatch 3500A form will consist of all data supplied such as 
Subject’s demography, SAE narrative, concomitant medication, laboratory parameters and relevant medical 
history. 
Copies of each report with the associated documentation (i.e., queries, medical records, lab records, 


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IRB/IEC communications and all source documents) will be kept in the site’s study file. 
A subject experiencing one or more SAEs will receive treatment and follow-up evaluations by the 
Investigator or may be referred to another appropriate physician for treatment and follow-up. The 
Investigational Site will be responsible for collection and forwarding follow-up SAE information to the 
Biorasi Safety and Pharmacovigilance. 
MEDICAL MONITOR 
Sergey Pavlenko, MD 
Medical Monitor 
Biorasi Safety and Pharmacovigilance 
email: spavlenko@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 888-1916  
7.6 Reporting of Pregnancies 
If a subject becomes pregnant during the participation in the study, the Investigator will immediately 
discontinue the patient from the study and contact the Medical Monitor, Biorasi Safety Team, and the 
Sponsor. Diligent efforts will be made to determine the outcome for all pregnancy exposures in the clinical 
trial. Information on the status of the mother and the child will be forwarded to the Biorasi Safety Team 
using the Pregnancy Data Collection Form. Generally, follow-up will occur within 6 to 8 weeks following 
the estimated delivery date. Any premature termination of the pregnancy will be reported. Detailed 
guidance on the reporting of Pregnancies will be provided in the SAE and Pregnancy Reporting Guidance. 
7.7 Unblinding due to SAE 
Patients, Investigators, site staff, Hyloris Developments SA and Biorasi will be blinded to treatment 
assignment.  
Reasons to unblind patient should be clearly documented in subject notes, and the monitoring site visit 
report. In the event of an emergency necessitating unblinding the PI/site staff will make every effort to 
contact and discuss the event with the Medical Monitor prior to unblinding. 
Treatment assignment for an individual subject should be unblinded only in an emergency by the 
Investigator, when knowledge of the treatment assignment is urgently needed for the clinical management 
or welfare of the subject. Treatment should be provided in accordance with the medical condition and 
according to the information provided in the Investigator’s Brochure. 
According to the FDA guidance Safety Assessment for IND Safety Reporting IND safety reports submitted 
should be unblinded. If the blind is broken and a subject with an adverse event that would meet the criteria 
for reporting as a single event was receiving placebo, the event will not be reported in an IND safety report 
because there is a reasonable possibility that the drug did not cause the adverse event. However, if the SAE 
is determined to be from drug exposure reporting to the FDA will take place.  


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The Investigator must document the breaking of the code, and the reasons for doing so on the CRF, in the 
site file, and in the medical notes. 
The Investigator must notify the Sponsor in writing as soon as possible following the code break detailing 
the necessity of the code break. Subject always to clinical need and where possible, all other members of 
the research team should remain blinded. 


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8 DATA ANALYSIS 
The sections below summarize the intended statistical methods and analyses of data for the study. A more 
detailed statistical analysis plan will be written prior to finalization of the clinical trial database. Any 
changes to the planned methods and analyses will be described and justified in the protocol and/or in the 
final clinical study report, as appropriate. 
Descriptive statistical methods will be used to summarize the data from this study, with confidence intervals 
calculated for the primary efficacy endpoints. Unless stated otherwise, the term “descriptive statistics” 
refers to number of subjects (n), mean, median, standard deviation (SD), minimum, and maximum for 
continuous data and frequencies and proportions for categorical data. The term “treatment group” refers to 
randomized treatment assignment: active-test and active-reference. All data collected during the study will 
be included in data listings. Unless otherwise noted, the data will be sorted first by treatment assignment, 
subject number, and then by date within each subject number. 
Unless specified otherwise, all statistical testing will be two-sided and will be performed using a 
significance (alpha) level of 0.05. 
All statistical analyses will be conducted with the SAS® System, version 9.4 or higher. 
8.1 Subject Population/Data Sets to Be Evaluated 
The subject populations are defined as follows: 
1. Safety Population: The safety population includes all randomized subjects who received and 
used study product. 
2. Modified Intent-to-Treat (mITT) Population: A modified intent-to-treat population includes 
all subjects who are randomized, applied at least one dose of assigned product, and returned for 
at least one post-baseline evaluation visit. 
3. Per Protocol (PP) Population: all randomized subjects who met all inclusion/exclusion criteria, 
had no protocol violations that would affect the treatment evaluation, were compliant with 
applying study product, and returned to the study site for the primary endpoint evaluation at four 
days (± 5 days) after the last day of the last cycle of treatment. Compliant subjects are defined as 
those who used at least 75% and no more than 125% of study drug doses until treatment success 
or four cycles of treatment. 
Subjects discontinuing due to “treatment failure” will be included in the PP population analysis as treatment 
failures, and will have alternative treatment recommended by the Investigator. Subjects discontinued 
prematurely from the study for any other reason (i.e., noncompliance, or withdrawal of consent, etc.) will 
be excluded from the PP population, but included in the mITT population, using Last Observation Carried 
Forward (LOCF). 
The results in the PP population will be considered definitive for therapeutic equivalence with those in the 
mITT population considered supportive. The results in the mITT population will be considered definitive 


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for superiority of each active treatment to placebo with those in the PP population considered supportive. 
Safety analyses will be performed using the Safety population. 
8.2 Sample Size Determination 
The difference in the proportion of subjects in the test and reference treatment groups who achieve 
“treatment success” defined as “total disappearance of all warts within all treated areas” at four days (± 5 
days) after the last day of the last cycle of treatment will be evaluated using a two-sided 90% confidence 
interval. The therapeutic equivalence of the test and reference products will be established if the confidence 
bounds of the 90% confidence interval are contained within the limits of -0.20 to +0.20.  The results in the 
PP population will be considered definitive for therapeutic equivalence with those in the mITT population 
considered supportive. 
Table 5. Sample Size Rationale 
Equivalency margin 
Power 
(%) 
CI 
(%) 
Sample Size mITT* 
(test: RLD: placebo) 
Sample Size PP* 
(test: RLD: placebo) 
20% 
85% 
90% 
392 
(168:168:56) 
350 
(150:150:50) 
* Sample sizes were calculated assuming: 40.0% success rate for active treatment, and 15.0% success rate for 
vehicle; 20% equivalency margin (EQ).  
8.3 Statistical Analyses 
8.3.1 Subject Disposition and Demography 
Descriptive statistics will be generated by treatment group for selected continuous variables. The number 
and percentage of subjects in each class of categorical demographic and baseline variables (e.g., gender, 
ethnicity, and race) will be tabulated by treatment group. Individual subject demographic and baseline 
characteristic data will be listed. 
8.3.2 Assessment of Bioequivalence as Primary Endpoint 
Bioequivalence assessment will be evaluated by comparing proportions of patients with treatment success 
in the test and the reference treatment groups. Bioequivalence between the test and the reference product 
will be established if the 90% confidence interval for the difference in success proportions between test and 
reference treatments is contained within the equivalence limits [-0.20, +0.20]. 
In this case, the compound hypothesis to be tested is: 
 (meaning test product is not bioequivalent to the reference); 
versus 
 (supporting bioequivalence); 


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where pT = success proportion of test treatment, pR = success proportion of reference treatment.  
Let  
1. nT = sample size of test treatment group 
2. c nT = number of subjects with success in test treatment group 
3. nR = sample size of reference treatment group 
4. c nR = number of subjects with success in reference treatment group 
 
and se = 
 
The 90% confidence interval will be estimated as follows, using Yates correction: 
 
H0 is rejected if L ≥ -0.20 and U ≤ 0.20 resulting in accepting HA and concluding bioequivalence of the two 
products. 
The primary endpoint is the evaluation of the proportion of subjects in each group with “treatment success” 
defined as “total disappearance of all warts within all treated areas”. The primary endpoint will be evaluated 
at four days (± 5 days) after the last day of the last cycle of treatment. The results in the PP population will 
be considered definitive, with those in the mITT population as supportive. 
8.3.3 Assessment of Superiority 
Superiority will be assessed through continuity-corrected Z-tests comparing each active treatment to 
placebo. If both the test and RLD success proportions are statistically significantly greater than the placebo 
proportion (p<0.05) then they will be considered superior to the placebo.  The results in the mITT 
population will be considered definitive for superiority with those in the PP population considered 
supportive. 
8.3.4 Assessment of Safety 
The reporting of safety data is descriptive, and will include all subjects who receive at least one dose of 
investigational product. The variables for safety endpoints are AEs, Local Application Site Reactions and 
vital signs measurements. AEs will be summarized based on the frequency of AEs and their severity for all 
treated subjects. All AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA) and 
summarized by treatment group. Data will be summarized using preferred term and primary system organ 
class. 


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If a subject experiences multiple events that map to a single preferred term, the greatest severity and 
strongest Investigator assessment of relation to study drug will be assigned to the preferred term for the 
appropriate summaries. Should an event have a missing severity or relationship, it will be classified as 
having the highest severity and/or strongest relationship to study drug. 
Summaries of treatment-emergent AEs will include any AEs reported beginning with the first dose of study 
drug on Day 1. The occurrence of treatment-emergent adverse events will be summarized by treatment 
group using preferred terms, system organ classifications, and severity. Separate summaries of treatment-
emergent serious adverse events, treatment-emergent adverse events related to study drug, and events 
leading to the discontinuation of study drug will be generated. All adverse events reported will be listed for 
individual subjects showing both verbatim and preferred terms. 
Concomitant medications will be coded using the World Health Organization (WHO) Drug Dictionary. 
These data will be summarized by treatment group. Previous and concomitant medications will be presented 
in a data listing. 
Local Application Site Reactions will be recorded at each study visit and will be summarized by the type 
of reaction (erythema, dryness, burning/stinging, erosion, edema, pain, itching and bleeding) and intensity 
score: 0=absent, 1=mild (slight, barely perceptible), 2=moderate (distinct presence), 3=severe (marked, 
intense). 
 
8.3.5 Comparability of Subjects at Baseline 
Descriptive statistics will be presented, by treatment group, for subject baseline characteristics. The 
significance of any obvious treatment group differences will be discussed in the CSR. 


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9 STUDY CONDUCT 
9.1 Ethical Conduct of the Study  
The study will be conducted according to the protocol, GCP, as outlined in the ICH Guidelines and Code 
of Federal Regulations. Written informed consent for the study must be obtained from all subjects before 
protocol specific procedures are performed. Subjects must be informed of their right to withdraw from the 
study at any time.  
9.2 Institutional Review Board (IRB) / Independent Ethics Committee 
(IEC) 
It is the responsibility of the Investigator to have prospective approval of the study protocol, protocol 
amendments, informed consent forms, and other relevant documents, (e.g., recruitment advertisements, 
subject’s diaries, if applicable) from the IRB/IEC. All correspondence with the IRB/IEC will be retained in 
the Investigator File. Copies of IRB/IEC approvals should be forwarded to the Sponsor or its designee. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is where the 
change is necessary to eliminate apparent immediate hazards to the subjects. In case of such an event, the 
Investigator must notify the IRB/IEC and the Sponsor in writing immediately after the implementation. 
9.3 Other Required Approvals 
In addition to IRB/IEC approval, all other required approvals (e.g. approval from local Research and 
Development Board or Scientific Committee) required by the individual site for participating in this study 
will be obtained by the Investigator prior to recruitment of subjects into the study and shipment of the 
investigational product(s). It is the responsibility of the Investigator to notify the Sponsor and the CRO of 
the requirement of such approvals prior to participating in the study. 
9.4 Informed Consent 
It is the responsibility of the Investigator to give each subject (or the subject’s acceptable representative), 
prior to inclusion in the trial, full and adequate verbal and written information regarding the objective and 
procedures of the trial and the possible risks involved. The subjects must be informed about their right to 
withdraw from the trial at any time. 
Furthermore, it is the responsibility of the Investigator, or a person designated by the Investigator, to obtain 
signed informed consent from each subject or the subject’s legally acceptable representative prior to 
inclusion in the trial. The Investigator will retain the original of each subject's signed consent form. 
The informed consent form will be in compliance to the ICH GCP, local regulatory, and legal requirements. 
The informed consent form used in this study, and any changes made during the study, must be 
prospectively approved by both the IRB/IEC and the Sponsor before use. 


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9.5 Subject Confidentiality 
All parties will ensure protection of subject personal data and will not include subject names on any Sponsor 
forms, reports, publications, or in any other disclosures, except where required by law. In case of data 
transfer, the Sponsor will maintain high standards of confidentiality and protection of subject personal data. 
However, in compliance with federal guidelines regarding the monitoring of clinical studies and in 
fulfillment of his/her obligations to Hyloris, it is required that the investigator permit the study monitor, 
any Hyloris authorized representative, and/or FDA representative to review that portion of the subject’s 
medical record that is directly related to the study.  This shall include all study relevant documentation 
including subject medical histories to verify eligibility, laboratory test result reports to verify transcription 
accuracy, admission/discharge summaries for hospital stays occurring while the subject is enrolled in the 
study and autopsy reports for deaths occurring during the study 
The Sponsor and designees affirm and uphold the principle of the subject’s right to protection against 
invasion of privacy. Throughout this study, a subject’s source data will only be linked to the Sponsor’s 
clinical study database or documentation via a unique identification number. As permitted by all applicable 
laws and regulations, limited subject attributes, such as sex, age, or date of birth, and subject initials may 
be used to verify the subject and accuracy of the subject’s unique identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the Sponsor requires 
the Investigator to permit its monitor or designee’s monitor, representatives from any regulatory authority 
(e.g., FDA), the Sponsor’s designated auditors, and the appropriate IRBs and IECs to review the subject’s 
original medical records (source data or documents), including, but not limited to, laboratory test result 
reports, admission and discharge summaries for hospital admissions occurring during a subject’s study 
participation, and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject as part of the informed consent process. As part of the required content of 
informed consent, the subject must be informed that his/her medical chart may be reviewed by Hyloris or 
their authorized representative, or a representative of the competent authorities (e.g. FDA).  Should access 
to the medical record require a separate waiver or authorization, it is the investigator’s responsibility to 
obtain such permission from the subject in writing before the subject is entered into the study. 
Copies of any subject source documents that are provided to the Sponsor must have certain personally 
identifiable information removed (i.e., subject name, address, and other identifier fields not collected on 
the subject’s CRF). 
9.6 Publication 
The Investigator is obliged to provide the sponsor with complete test results and all data derived by the 
Investigator from the study. During and after the study, only the sponsor may make study information 
available to other study Investigators or to regulatory agencies, except as required by law and regulation. 
Except as otherwise allowable in the Clinical Study Site Agreement, any public disclosure related to the 
protocol or study results is the sole responsibility of the sponsor.  
The sponsor may publish any data and information from the study (including data and information 
generated by the Investigator) without the consent of the Investigator.  


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Manuscript authorship for any peer-reviewed publication by Investigator will appropriately reflect 
contributions to the production and review of the document. The Sponsor must have the opportunity to 
review and approve all proposed abstracts, manuscripts, or presentations regarding this study prior to 
submission for publication/presentation. The Sponsor keeps the right to delete prior to submission any 
information identified by the Sponsor as confidential. All publications and presentations must be prepared 
in accordance with this section and the Clinical Study Site Agreement. In the event of any discrepancy 
between the protocol and the Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail. 
9.7 Protocol amendments 
The Investigator will not make any changes to this protocol without prior written consent from Hyloris and 
subsequent approval by the IRB.  Any permanent change to the protocol, whether it is an overall change or 
a change for specific study center(s), must be handled as a protocol amendment. Any amendment to the 
protocol that appears indicated as the study progresses will be fully discussed between Biorasi and Hyloris. 
However, a protocol change intended to eliminate an apparent immediate hazard to subjects should be 
implemented immediately, and the IRB notified within five days.   
 
 


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10 ADMINISTRATIVE OBLIGATIONS 
10.1 Source Documentation Forms 
The Investigator/institution will permit study-related monitoring, audits/inspections, IRB/IEC review and 
regulatory inspection providing direct access to source documents, including all medical records or 
pertinent data relevant to the audit/inspection. Source documents will represent a record of the raw data. 
Source document templates may be provided by either the clinical site or the Sponsor. If provided by the 
clinical site, the source document template must be provided to the Sponsor prior to subject recruitment. 
The source documents will become part of the subject's permanent medical record maintained by the clinical 
site. If computerized systems are used to create, modify, maintain, archive, retrieve or transmit source data, 
they must comply with the applicable regulatory regulations and/or guidances (ex. 21 CFR Part 11 and 
312). 
ECRFs will be used in this study. ECRFs are required and should be completed for each subject 
participating in the study. ECRFs will contain data captured from subject source documents and results of 
laboratory tests. In most cases, the source documents are contained in the subject’s chart at the hospital or 
the physician's office. In these cases, data collected on the CRFs must match the data in those charts. Data 
must be transcribed from the source documents (e.g. physical exam report, associated medical records, date 
and version of informed consent form) onto the CRF by clinical site personnel prior to data monitoring.  
Any corrections to entries made in the source documents must be dated, initialed and explained (if 
necessary) and should not obscure the original entry. The Investigator has ultimate responsibility for the 
accuracy, authenticity, and timely collection and reporting of all clinical, safety, and laboratory data entered 
on the CRFs and any other data collection forms.  
Investigator will sign eCRFs electronically after completion of data entry, to attest that the data contained 
on the CRFs is complete and accurate. Completed eCRFs are the sole property of the Sponsor and should 
not be made available in any form to third parties, except for authorized representatives of the Sponsor or 
appropriate regulatory authorities, without written permission from the Sponsor. 
10.2 Record Retention 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator agrees to 
keep records, including the identity of all participating subjects (sufficient information to link records, e.g., 
CRFs and hospital records), all original signed Informed Consent Forms, copies of all CRFs, SAE forms, 
source documents, detailed records of drug disposition, and adequate documentation of relevant 
correspondence (e.g., letters, meeting minutes, telephone calls reports).  
The records will be retained by the Investigator according to the International Conference on Harmonization 
(ICH), local regulations, or as specified in the Clinical Study Agreement, whichever is longer. 
If the Investigator becomes unable for any reason to continue to retain study records for the required period 
(e.g., retirement, relocation), the Sponsor will be prospectively notified. The study records must be 
transferred to a designee acceptable to the Sponsor, such as another Investigator, another institution, or to 


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the Sponsor. The Investigator must obtain Sponsor’s written permission before disposing of any records, 
even if retention requirements have been met. 
10.3 Quality Control (QC) and Quality Assurance (QA) 
10.3.1 Study Site Monitoring Visits 
During study conduct, the Sponsor or its designee will conduct periodic monitoring visits to ensure that the 
protocol and Good Clinical Practice (GCP) are being followed. The monitors will follow study Monitoring 
Plan to review source documents to confirm that the data recorded on CRFs is accurate. The 
Investigator/institution will allow the Sponsor’s monitors or designees and appropriate regulatory 
authorities direct access to source documents to perform this verification. 
The study site may also be subject to quality assurance audits performed by the Sponsor or companies 
working with or on behalf of the Sponsor, and/or review by the IRB/IEC, and/or to inspection by appropriate 
regulatory authorities. 
It is important that the Investigator(s) and their relevant personnel are available during the monitoring visits 
and possible audits or inspections, and that sufficient time is devoted to the process. 
10.3.2 Protocol Deviations 
The protocol must be read thoroughly and the instructions must be followed. Investigator will not 
implement any protocol deviations or modification without prior approval of the Sponsor, IRB/IEC and 
regulatory authorities, as required. However, exceptions will be made in emergency situations when the 
protection, safety, and well-being of the patient requires immediate intervention based on the judgment of 
the Investigator or a responsible, appropriately trained, and credentialed professional(s) designated by the 
Investigator as a sub-investigator.  
In the event of a protocol deviation due to an emergency, accident, or error, the Investigator or designee 
must contact the Medical Monitor at the earliest possible time by email or telephone. This allows for an 
early joint decision to be made as to whether the patient should continue in the study. The Investigator, the 
Sponsor, and the Medical Monitor will document this decision. In the event of a deviation, the Investigator 
will notify the Sponsor or its designee (and IRB or IEC, as required). 
10.4 Trial Discontinuation/Investigative Site Termination 
The Sponsor reserves the right to discontinue the trial prior to inclusion of the intended number of subjects.  
After such a decision, the Investigator must contact all participating subjects within a specified timeframe 
established by the Sponsor to inform them of the decision to discontinue the trial. 
10.4.1 Criteria for Premature Termination or Suspension of the Study 
The following criteria may result in either temporary suspension or early termination of the study: 
 
New information regarding the safety or efficacy of the Study Drug that indicates a change in the 


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known risk/benefit profile for the compound, such that the risk/benefit is no longer acceptable for 
subjects participating in the study. 
 
Significant violation of GCP that compromises the ability to achieve the primary study objectives 
or compromises subject safety. 
The Sponsor reserves the right to discontinue the trial for other valid administrative reasons. 
10.4.2 Criteria for Premature Termination or Suspension of Investigational Sites 
A study site may be terminated prematurely or suspended if the site (including the Investigator) is found to 
be in significant violation of GCP, protocol, contractual agreement, or is unable to ensure adequate 
performance of the study. 
10.4.3 Procedures for Premature Termination or Suspension of the Study or 
Investigational Site(s) 
Should the Sponsor elect to terminate or suspend the study or the participation of an investigational site, a 
study-specific procedure for early termination or suspension will be provided by the Sponsor. The 
procedure will be followed by applicable investigational sites during the course of termination or study 
suspension. 


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11 REFERENCES 
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Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation : A Reference Guide to 
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Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR. Optimal frequency of imiquimod 
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Baker DA, Ferris DG, Martens MG, et al. Imiquimod 3.75% cream applied daily to treat anogenital 
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Kumar B, Narang T. Local and systemic adverse effects to topical imiquimod due to systemic 
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Tatti S, Swinehart JM, Thielert C, Tawfik H, Mescheder A, Beutner KR. Sinecatechins, a defined 
green tea extract, in the treatment of external anogenital warts: a randomized controlled trial. Obstet 
Gynecol. 2008;111(6):1371-1379. doi:10.1097/AOG.0b013e3181719b60. 
10.  
Gross G, Meyer K-G, Pres H, Thielert C, Tawfik H, Mescheder A. A randomized, double-blind, 
four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of 
two galenic formulations of Polyphenon E in the treatment of external genital warts. J Eur Acad 
Dermatol Venereol. 2007;21(10):1404-1412. doi:10.1111/j.1468-3083.2007.02441.x. 
11.  
Stockfleth E, Beti H, Orasan R, et al. Topical Polyphenon E in the treatment of external genital and 
perianal warts: a randomized controlled trial. Br J Dermatol. 2008;158(6):1329-1338. 
doi:10.1111/j.1365-2133.2008.08520.x. 
12.  
von Krogh G. Podophyllotoxin in serum: absorption subsequent to three-day repeated applications 
of a 0.5% ethanolic preparation on condylomata acuminata. Sex Transm Dis. 9(1):26-33. 
http://www.ncbi.nlm.nih.gov/pubmed/10328020. Accessed June 5, 2016. 
13.  
Tyring S, Edwards L, Cherry LK, et al. Safety and Efficacy of 0.5% Podofilox Gel in the Treatment 
of Anogenital Warts. Arch Dermatol. 1998;134(1):33. doi:10.1001/archderm.134.1.33. 
14.  
Actavis Pharma I. Physician Information Condylox ® Gel 0.5% ( podofilox gel) (con’ de lox) 
Content 
Updated: 
August 
2014 
Rx 
only 
140348. 
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ada310c0-0811-4e6b-97cc-


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9653b17d66d8&type=display. Published 2014. Accessed August 12, 2016. 
15.  
Hyloris Developments SA. Investigator’s Brochure for Podofilox Gel 0.5%. 1st ed.; 2016. 
16.  
Food and Drud Administration. Draft Guidance on Podofilox.; 2012. 
17.  
Food and Drug Administration. Guidance for Industry - Handling and Retention of BA and BE 
Testing Samples.; 2004. 
 


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12 APPENDICES 
12.1 Appendix A. Study Flowchart 
 
 


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12.2 Appendix B. Schedule of Events 
Study Visit 
Screening 
Visit 1 
Baseline 
Visit 2 
Treatment Period 
Visit 3 
Visit 4 
Visit 5 
EOS/ET 
Visit 6 
Visit Day 
Day -14 
to -1 
Day 0 
Day 7 (±1 
day) 
Day 14 
(±1 day) 
Day 21 
(±1 day) 
Day 28 
(±5 day) 
Informed Consent 
X 
 
 
 
 
 
Subject Demographics 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Concomitant and Prohibited Therapies 
Review 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
X 
 
 
 
X 
Visual Inspection of EAWs1 
X 
X 
X 
X 
X 
X 
Serology test for HIV2 
X 
 
 
 
 
 
Test for Hepatitis B, C 
X 
 
 
 
 
 
Test for Syphilis3 
X 
 
 
 
 
 
Urine Pregnancy Test 
X 
X 
 
 
 
X 
Eligibility Criteria Check 
X 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Training on Study Drug Application  
 
X 
 
 
 
 
Training on Subject Diary Card completion 
and contraception methods  
 
X 
 
 
 
 
Study Drug Dispensation 
 
X 
X 
X 
X 
 
Assessment of Local Application Site 
Reactions 
 
X 
X 
X 
X 
X 
Adverse Events Assessment 
X 
X 
X 
X 
X 
X 
Study Drug Return and Accountability 
 
 
X 
X 
X 
X 
Subject Diary Card Return and Review 
 
 
X 
X 
X 
X 
Subject Diary Card Dispensation 
 
X 
X 
X 
X 
 
Histological confirmation of diagnosis4 
X 
 
 
 
 
 
 
                                                     
 
1 If total disappearance of all warts is achieved within all treated areas at visits 2, 3, 4, or 5, respective visit will be 
considered an End of Study (EOS) visit. In the case where reduction of warts is absent or incomplete, a new treatment 
cycle will be initiated for a maximum of four cycles in total for the subject. 
2 Test may not be repeated if the subject has negative HIV test results within 4 weeks before Baseline. Copy of the 
test result needs to be filed with the study records. 
3 If required by applicable local regulations. 
4 Histological confirmation will be obtained if there is any doubt of the diagnosis. 

SAP_001.pdf: 
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STATISTICAL ANALYSIS PLAN 
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STATISTICAL ANALYSIS PLAN 
PHASE III 
VERSION: 1.0 
DATE OF PLAN: 
27-May-2019 
BASED ON: 
Protocol Version 2.0 15-Jan-2018 
Data Management Plan Final Version 1.0 02-Feb-2018 
Study Drug: 
Test Drug: Podofilox Topical Gel 0.5% (Hyloris Developments SA) 
 RLD: Condylox® Gel 0.5% (Allergan Pharmaceuticals) 
Protocol Number: 
016-POD-001 
Study Title: 
A Mulit-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study of 
Hyloris Development’s Podofilox Topical Gel 0.5% compared to Allergan’s Condylox® Gel 
0.5%, and both active treatments to a vehicle control in male and female patients with external 
Anogenital Warts. 
Sponsor: 
Hyloris Developments SA 
Bâtiment GIGA EE1 
Avenue Hippocrate n° 5 
4000 Liège (Sart-Tilman) 
Belgium 






 
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PROTOCOL SYNOPSIS 
Study Title 
A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-
Controlled, Study of Hyloris Developments’s Podofilox Topical Gel 
0.5% compared to Allergan’s Condylox® Gel 0.5% in male and female 
patients with external anogenital warts. 
Protocol Number 
016-POD-001 
Development Phase 
3 
Type of Study 
Bioequivalence (BE) with Clinical Endpoints. 
Study Medication:  
1) Podofilox Topical Gel 0.5% (Test formulation), manufactured by 
Hyloris Developments. 
2) Condylox® Gel 0.5% (Reference Product), manufactured by 
Allergan Pharmaceuticals. 
3) Vehicle of test product, manufactured by Hyloris Developments SA. 
Name of Active 
Ingredient 
Podofilox 
Route of 
administration 
Topical application 
Sponsor 
Hyloris Developments SA 
Bâtiment GIGA EE1 
Avenue Hippocrate n° 5 
4000 Liège (Sart-Tilman) 
Belgium. 
Study Objectives 
PRIMARY 
• To compare the clinical efficacy among patients with anogenital 
warts when treated with Podofilox Topical Gel 0.5% or 
Condylox® Gel 0.5% or placebo. 
SECONDARY  
• To demonstrate safety of Podofilox Topical Gel 0.5% compared 
to Condylox® Gel 0.5% or placebo assessed by the frequency and 
severity of adverse events, and application site reaction scores 


 
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(erythema, dryness, burning/stinging, erosion, edema, pain, 
itching and bleeding). 
Study Design 
This is a multicenter, parallel group, randomized, double-blind, placebo-
controlled, trial with clinical endpoint comparing Podofilox Topical Gel 
0.5% to Condylox® Gel 0.5% and a matching placebo. The study will be 
conducted among adult male and female patients with external anogenital 
warts.  
All study related procedures will be conducted only after written 
informed consent is obtained at the Screening visit, which will occur up 
to 14 days prior to the Baseline (Days -14 to -1). During the Screening 
visit, the Investigator will record subject’s demographics, medical 
history, review concomitant medication, identifying any prohibited 
therapies that subject is currently taking.  
The Investigator will assess vital signs and perform physical examination 
identifying any clinically significant abnormalities. Laboratory samples 
will be collected, including HIV, Hepatitis B&C and urine pregnancy 
tests (UPT) for women of childbearing potential. The Investigator will 
confirm the diagnosis of External Anogenital Warts (EAW) and the 
absence of contraindications specified in the exclusion criterion 4 during 
the visual examination. The biopsy of skin lesions will be performed per 
the discretion of the Investigator for microscopic verification of the 
diagnosis of EAWs if any doubts of the diagnosis. 
Once the results of Screening assessments are obtained, suggesting that 
the subject is eligible for entering the study, the Baseline visit (Day 0) 
will take place. During this visit, the Investigator will identify any AEs 
that occurred from the last visit, review concomitant and prohibited 
therapies, perform vital signs and physical examination. Those subjects 
who qualify for entering the study will be randomized to one of the 
following arms in a ratio of 3:3:1: 
• Arm 1 (Test product): Subjects in this arm will receive test 
formulation of Podofilox Topical Gel 0.5% (Hyloris Developments 
SA). 
• Arm 2 (Reference Listed Drug [RLD]): Subjects in this arm will 
receive RLD Condylox® Gel 0.5% (Allergan Pharmaceuticals). 


 
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• Arm 3 (Placebo): Subjects in this arm will receive a vehicle that 
matches the test product, except for the inclusion of the active 
ingredient (Hyloris Developments SA). 
Randomization and study medication number assignment will be 
performed using an Interactive Web Response System (IWRS).  
EAWs will be inspected and the count of EAWs will be captured in the 
source worksheet and electronic Case Report Form (eCRF). The 
Investigator will assess the baseline level of Local Application Site 
Reactions, recording the scores based on the Local Application Site 
Reactions Scale. 
During the inspection of EAWs, study physician (Principal Investigator 
(PI), or Sub-Investigator) will train the subject on proper application of 
the study drug using the properly labeled demonstration tube (contains 
vehicle of the study drug) and applicator.  The subject will be trained to 
apply the study drug to the surface of the warts at a proper amount (not 
to exceed 0.5 g per day or 0.25 g per application), avoiding unaffected 
and wounded skin areas, and to let the gel dry completely before allowing 
the return of opposing skin surfaces to their normal positions. Mirrors are 
to be used in order to facilitate process of application. Subjects will be 
instructed to not use the study drug in the vagina or in the rectum, and 
remove medication from any areas that experience stinging or burning 
immediately upon application. Site staff will also visually show the 
subjects what the correct amount of drug to be used per application looks 
like. 
The subject will also be trained on Patient’s Diary Card Completion and 
Contraception Methods. The subject will be given a study drug, mirror 
and a Patient’s Diary Card to capture application details, and 
acknowledge any changes in skin reactions, other AEs and concomitant 
medications during the intervening time between the site visits. 
On the following day after the Baseline visit (Day 1) the subject will apply 
the study drug on EAWs following the recommendations given during 
training at the clinic site. The treatment phase will consist of four weekly 
treatment cycles at a maximum, during which the drug will be applied 
twice a day (in the morning and at the bedtime) for 3 consecutive days, 
then discontinuing for 4 consecutive days. Study drug will thus be applied 
only on Days 1, 2, 3, 8, 9, 10, 15, 16, 17, 22, 23 and 24. 


 
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Study visits will occur on the seventh (7) day of each treatment cycle: on 
Day 7 (Week 1), Day 14 (Week 2), Day 21 (Week 3), and Day 28 (Week 
4). Primary endpoint (total disappearance of all treated warts) will be 
evaluated during each of these visits. In case the primary endpoint is 
reached at any of the visits prior to the Day 28 visit, it will be considered 
as End of Study (EOS) visit – the Investigator will perform physical 
examination and repeat urine pregnancy test, and subject’s participation 
will be considered complete. If total disappearance of warts is not 
achieved, a new treatment cycle will be initiated for a maximum of four 
cycles in total for the subject. 
During each study visit, the Investigator will collect vital signs, evaluate 
EAWs for absence or present, capturing the count of EAWs, record Local 
Application Site Reactions and adverse events (AEs), assess Patient’s 
Diary Card completion and subject’s compliance with the study drug 
application, review concomitant medication and confirm that there were 
no prohibited therapies applied from the last visit.  
In the event the primary endpoint (total disappearance of all warts within 
all treated areas) has been achieved prior to the Day 28 visit, this visit will 
be considered End of Study (EOS) visit. In case a subject discontinues 
prematurely, the Investigator will conduct an Early Termination (ET) 
visit, capturing the reason for discontinuation and performing 
assessments of EOS visit. 
Number of Subjects 
and Sites 
The planned overall sample size for this clinical trial is approximately 
413 adult male and female subjects with external anogenital warts, who 
will be randomized at a 3:3:1 ratio (test:RLD:placebo) at about 16 clinical 
research centers in the United States, Russia and Ukraine. mITT and PP 
population size will be approximately 392 and 350 correspondingly. 
Eligibility Criteria 
Subjects who satisfy ALL of the following inclusion and have NONE of 
the following exclusion criteria may be enrolled in the study: 
INCLUSION CRITERIA 
1. Willing and able to provide written informed consent prior to 
participating in this study. 
2. Male or female subjects, aged 18-65 inclusive, with a clinical 
diagnosis of external anogenital warts (i.e., perianal warts and/or 
external genital warts), including two or more distinct external genital 


 
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warts, and wart area that is equal or less than 10 cm2.  Histological 
confirmation should be obtained if there is any doubt of the diagnosis. 
3. Females of childbearing potential may be enrolled if they practice a 
method of birth control with a reliability of at least 90% and agree to 
continue doing so throughout the treatment period. 
4. In addition to birth control method with high reliability, sexually 
active study participants must use a barrier protection method of 
contraception such as male or female condom or abstinence 
throughout the treatment period in order to prevent cross- and 
reinfestation by Human Papilloma Virus (HPV).  
5. Any female subject with childbearing potential has a negative urine 
pregnancy test on first day of dosing (study Day 1). 
6. Negative HIV test within 4 weeks before the first day of dosing (study 
Day 1). 
EXCLUSION CRITERIA 
1. Female subjects who are pregnant or lactating or planning to become 
pregnant during the study period. 
2. Hypersensitivity or intolerance to Podofilox or any component of the 
formulation. 
3. History of previous unsuccessful treatment with any formulation of 
Podofilox. 
4. Wart area that is greater than 10 cm2. 
5. Patients with internal anogenital and mucous membrane warts, 
bowenoid papulosis, squamous cell carcinoma, active herpes lesion, 
or other skin abnormalities of treatment area, such as eczema, or skin 
that had not healed following surgery (cryosurgery, laser ablation or 
similar). 
6. Primary or secondary immunodeficiency. 
7. Known presence of diabetes type I or II. 
8. Local irritation in any treatment area that would interfere with 
treatment. 
9. Use within 4 weeks prior to baseline of any: 1) treatment for 
anogenital warts, 2) systemic corticosteroids, or 3) systemic 
immunosuppressive drug. 
10. Any medical or surgical condition in the judgment of the Investigator 
that may interfere with the assessment of efficacy or safety, or pose 
a risk to the subject. 
11. Patients known to abuse alcohol and/or drugs, or with a history of 
chronic alcohol or drug abuse that may result in protocol non-
compliance. 


 
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12. Received another investigational drug, device or biologic within 30 
days prior to the start of Screening or has planned to participate in 
another clinical trial while enrolled in this study. 
13. Subjects who in the opinion of the investigator, are unlikely to be 
able to follow the restrictions of the protocol and complete the study. 
14. Employee (or employee’s family member) of the research center or 
private practice, CRO or Sponsor, or subjects who have a conflict of 
interest.  
15. Subjects living (e.g., siblings, spouses, relatives, roommates) in the 
same household cannot be enrolled in the study at the same time. 
16. Previous enrollment in this study, current enrollment in this study at 
another participating site or current enrollment in another study (in 
parallel to this study) at another clinical research site. 
Withdrawal and 
Early 
Discontinuation 
Subjects whose condition worsens and require alternate or supplemental 
therapy for the treatment of external anogenital warts during the study 
should be discontinued, and the Early Termination visit must be 
performed. 
Prohibited 
Concomitant 
Medication 
Use of following therapies is prohibited during study participation:  
• Any other topical products applied to the treatment area(s). 
• Systemic corticosteroid or immunosuppressive drugs. 
• Antipruritics, including antihistamines, in the 24 hours prior to study 
visits. 
Study Drug 
Study drug includes Test, Reference and Placebo drug products. The 
Sponsor will supply study drug as matching 3.5 g of clear gel in 
aluminum tubes with an applicator tip, labeled for a blinded study. 
• Test Drug: Podofilox Topical Gel 0.5% (Hyloris Developments SA). 
• RLD: Condylox® Gel 0.5% (Allergan Pharmaceuticals). 
• Placebo: Vehicle of the test drug (Hyloris Developments SA). 
Storage temperature is 20-25°C (68-77°F). 
Duration of Patient 
Study Participation 
Up to 50 Days. 
Study Endpoints 
PRIMARY 


 
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• The primary endpoint is the proportion of subjects in the per protocol 
(PP) population with “treatment success” defined as “total 
disappearance of all warts within all treated areas”. 
SECONDARY (Safety Endpoints) 
• Local application site reactions scores (erythema, dryness, 
burning/stinging, erosion, edema, pain, itching and bleeding) in each 
group during the study drug application period. 
• Other adverse events including serious adverse events throughout the 
study participation. 
Statistical Analysis 
EFFICACY ANALYSIS 
The difference in the proportion of subjects in the test and reference 
treatment groups who achieve “treatment success” defined as “total 
disappearance of all warts within all treated areas” at four days (± 5 days) 
after the last day of the last cycle of treatment will be evaluated using a 
two-sided, continuity-corrected 90% confidence interval. The therapeutic 
equivalence of the test and reference products will be established if the 
confidence bounds of the 90% confidence interval are contained within 
the limits of -0.20 to +0.20.  The results in the per-protocol (PP) 
population will be considered definitive for therapeutic equivalence with 
those in the modified Intent-To-Treat (mITT) population considered 
supportive. 
Superiority will be assessed through continuity-corrected Z-tests 
comparing each active treatment to placebo. If both the test and RLD 
success proportions are statistically significantly greater than the placebo 
proportion (p<0.05, two-sided) then they will be considered to be superior 
to the placebo.  The results in the mITT population will be considered 
definitive for superiority with those in the PP population considered 
supportive. 
Subjects discontinuing due to “treatment failure”, defined as worsening 
of condition and requiring alternate or supplemental therapy for the 
treatment of external anogenital warts during the study, will be included 
in the PP population analysis as treatment failures, and provided with 
effective treatment. Subjects discontinued prematurely from the study for 
any other reason (i.e., noncompliance, or withdrawal of consent, etc.) will 
be excluded from the PP population, but included in the mITT population, 
using Last Observation Carried Forward (LOCF). 
SAFETY ANALYSIS 


 
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Safety data analysis will include local application site reaction scores 
(erythema, dryness, burning/stinging, erosion, edema, pain, itching and 
bleeding), reported adverse events, vital signs and concomitant 
medication assessments summarized by treatment group and time point 
of collection, when appropriate. 
Descriptive statistics (arithmetic mean, standard deviation (SD), 
coefficient of variation (CV), median, minimum, and maximum) will be 
calculated for quantitative safety data as well as for the difference from 
baseline, when appropriate. 
Adverse events will be coded using the most recent version of the Medical 
Dictionary of Regulatory Activities (MedDRA®) noted in the Statistical 
Analysis Plan. A subject AE listing by MedDRA® system organ class and 
by preferred term within system organ class, including verbatim term, 
dose level, severity, and relationship to treatment, will be provided. This 
listing will include all AEs and serious adverse events (SAEs). Adverse 
events will also be presented in summary tables. Concomitant 
medications will be listed by treatment and coded using the most recent 
version of the World Health Organization (WHO) Drug Dictionary. 
 
 
 


 
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1 TABLE OF CONTENTS 
1 
TABLE OF CONTENTS ...................................................................................................... 11 
2 
LIST OF ABBREVIATIONS ............................................................................................... 14 
3 
INTRODUCTION ................................................................................................................. 15 
3.1 
Study Overview ............................................................................................................ 15 
3.2 
Schedule of Events ........................................................................................................ 16 
4 
STUDY OBJECTIVE AND ENDPOINTS ........................................................................... 17 
4.1 
Study Objectives ........................................................................................................... 17 
4.2 
Study Endpoints ............................................................................................................ 17 
4.2.1 
Primary Endpoint .................................................................................................... 17 
4.2.2 
Secondary (Safety) Endpoints ................................................................................. 17 
5 
STUDY DESIGN .................................................................................................................. 18 
5.1 
Summary of Study Design ............................................................................................ 18 
5.2 
Definition of Study Drugs ............................................................................................. 19 
5.3 
Sample Size Considerations .......................................................................................... 19 
6 
PLANNED ANALYSIS ........................................................................................................ 19 
7 
GENERAL CONSIDERATION FOR DATA ANALYSIS AND HANDLING .................. 20 
7.1 
General Summary Table and Individual Subject Data Listing ..................................... 20 
7.2 
General Summary Table and Individual Subject Data Listing Considerations ............ 21 
7.3 
Data Management ......................................................................................................... 22 
7.4 
Data Presentation Conventions ..................................................................................... 22 
7.5 
Analysis Populations ..................................................................................................... 23 


 
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7.5.1 
Definitive and Supplemetal..................................................................................... 23 
7.5.2 
Screen Failures ........................................................................................................ 23 
7.5.3 
Protocol Deviations ................................................................................................. 24 
7.5.4 
Safety Population .................................................................................................... 24 
7.5.5 
Modified Intent-to-Treat (mITT) Population .......................................................... 24 
7.5.6 
Per-Protocol (PP) Population .................................................................................. 24 
7.6 
Baseline Definition ....................................................................................................... 25 
7.6.1 
Baseline Age ........................................................................................................... 25 
7.6.2 
Study Day................................................................................................................ 26 
7.6.3 
Visit Windows ........................................................................................................ 26 
7.6.4 
Multiple Assessments ............................................................................................. 27 
7.6.5 
Handling of Missing Data ....................................................................................... 27 
7.6.6 
Missing Start and Stop Dates for Prior and Concomitant Medication.................... 27 
7.6.7 
Missing Start and Stop Dates for Adverse Events .................................................. 27 
8 
STUDY POPULATION ........................................................................................................ 29 
8.1 
Subject Disposition ....................................................................................................... 29 
8.2 
Protocol Deviations ....................................................................................................... 29 
8.3 
Demographic and Baseline Characteristics .................................................................. 29 
8.4 
Medical History ............................................................................................................ 29 
9 
EFFICACY ANALYSES ...................................................................................................... 30 
9.1 
Primary Efficacy Endpoint ........................................................................................... 30 
9.1.1 
  Bioequivalence Analysis ....................................................................................... 30 


 
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9.1.2 
Superiority Analysis................................................................................................ 31 
10 
SAFETY ANALYSES....................................................................................................... 32 
10.1 
Safety Endpoints ........................................................................................................... 32 
10.1.1 
Adverse Events ....................................................................................................... 32 
10.1.2 
Local Application Site Reactions............................................................................ 33 
10.1.3 
Vital Signs ............................................................................................................... 33 
11 
REFERNCES ..................................................................................................................... 34 
12 
Appendix ............................................................................................................................ 35 
12.1 
APPENDIX A. Tables and Listings.............................................................................. 35 
12.1.1 
List of Tables .......................................................................................................... 35 
12.1.2 
List of Listings ........................................................................................................ 68 
 
 
 


 
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2 LIST OF ABBREVIATIONS 
AE 
Adverse Event 
BE 
Bioequivalence 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CV 
Coefficient of Variation 
DD 
Drug Dictionary 
EAW 
External Anogenital Warts 
eCRF 
Electronic Case Report Form 
EOS 
End of Study 
ET 
Early Termination 
g 
Gram 
GCP 
Good Clinical Practice 
H 
Hours 
HIV 
Human Immunodeficiency Virus 
HPV 
Human Papilloma Virus  
ICH 
International Conference on Harmonization 
IWRS 
Interactive Web Response System 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary of Regulatory Activities 
mITT 
Modified Intent-To-Treat 
PD 
Protocol Deviation 
PI 
Principal Investigator 
PP 
Per-Protocol 
PV 
Protocol Violation 
PVPD 
Protocol Violation and Protocol Deviation 
RLD 
Referenced Listed Drug 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 


 
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TEAE 
Treatment Emergent Adverse Event 
UPT 
Urine Pregnancy Test 
WHO 
World Health Organization 
 
3 INTRODUCTION 
This document describes the statistical methods and data presentations to be used in the summary 
and analysis of data from Protocol 016-POD-001 version 2.0 dated 15Jan2018. Background 
information is provided for the overall study design and objectives. The reader is referred to the 
study protocol and electronic case report forms (eCRFs) for details of study conduct and data 
collection. 
3.1 Study Overview 
Clinical study of protocol 016-POD-001 is a multicenter, parallel group, randomized, double-
blind, placebo-controlled, trial with clinical endpoint comparing Podofilox Topical Gel 0.5% to 
Condylox® Gel 0.5% and a matching placebo. The study will be conducted in adult male and 
female patients with external anogenital warts. The study also assesses comparative safety of 
Podofilox Topical Gel 0.5% and Condylox® Gel 0.5%. 
Safety data analysis will include local application site reaction scores (erythema, dryness, 
burning/stinging, erosion, edema, pain, itching and bleeding), reported adverse events, vital signs 
and concomitant medication assessments summarized by treatment group and time point of 
collection, when appropriate. 
The primary objective is to compare the clinical efficacy among patients with anogenital warts 
when treated with Podofilox Topical Gel 0.5% versus Condylox® Gel 0.5% and placebo. The 
secondary objective is to demonstrate safety of Podofilox Topical Gel 0.5% compared to 
Condylox® Gel 0.5% and placebo assessed by the frequency and severity of adverse events, and 
application site reaction scores (erythema, dryness, burning/stinging, erosion, edema, pain, itching, 
and bleeding).  
The planned overall sample size for this clinical trial is approximately 413 adult male and female 
patients with external anogenital warts, who will be randomized at a 3:3:1 ratio (test: RLD: 
placebo) at about 16 clinical research centers in the United States, Russia and Ukraine. The mITT 
and PP population sizes will be approximately 392 and 350, correspondingly. A subject is 
considered enrolled after he/she has provided a signed informed consent and begins the screening 
process. A subject is considered randomized upon receiving his/her randomized treatment 
assignment.  


 
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The entire study will consist of a maximum of 6 visits: 
1. Visit l (Day -14 up to -1): Screening Evaluations at the Study Site performed. 
2. Visit 2 (Day 0): Study Drug Dispensation. 
3. Visit 3-5 (Day 7 ±1 [Week 1], Day 14 ±1 [Week 2], and Day 21 ±1 [Week 3]: Follow-up 
of the Study Drugs. 
4. Visit 6 (Day 28 ± 5 [Week 4]): End of Study Visit / Early Termination Visit at the Study 
Site including Safety and Efficacy Evaluation. 
3.2 Schedule of Events 
Table 2.2.1 Study visits and assessments. 
Study Visit 
Screening 
Visit 1 
Baseline 
Visit 2 
Treatment Period 
Visit 3 
Visit 4 
Visit 5 
EOS/ET 
Visit 6 
Visit Day 
Day -14 to 
-1 
Day 0 
Day 7 
(±1) 
Day 14 
(±1) 
Day 21 
(±1) 
Day 28 
(±5) 
Informed Consent 
Χ 
 
 
 
 
 
Subject Demographics 
Χ 
 
 
 
 
 
Medical History 
Χ 
 
 
 
 
 
Concomitant and Prohibited 
Therapies Review 
Χ 
Χ 
Χ 
Χ 
Χ 
Χ 
Vital Signs 
Χ 
Χ 
Χ 
Χ 
Χ 
Χ 
Physical Examination 
Χ 
Χ 
 
 
 
Χ 
Visual Inspection of EAWs1 
Χ 
Χ 
Χ 
Χ 
Χ 
Χ 
Serology test for HIV2 
Χ 
 
 
 
 
 
Test for Hepatitis B, C 
Χ 
 
 
 
 
 
Test for Syphilis3 
Χ 
 
 
 
 
 
Urine Pregnancy Test 
Χ 
Χ 
 
 
 
Χ 
Eligibility Criteria Check 
Χ 
Χ 
 
 
 
 
Randomization 
 
Χ 
 
 
 
 
Training on Study Drug 
Application 
 
Χ 
 
 
 
 
Training on Subject Diary Card 
Completion and Contraception 
Methods 
 
Χ 
 
 
 
 
Study Drug Dispensation 
 
Χ 
Χ 
Χ 
Χ 
 
Assessment of Local Application 
Site Reactions 
 
Χ 
Χ 
Χ 
Χ 
Χ 
Adverse Events Assessment 
Χ 
Χ 
Χ 
Χ 
Χ 
Χ 
Study Drug Return and 
Accountability 
 
 
Χ 
Χ 
Χ 
Χ 
Subject Diary Card Return and 
Review 
 
 
Χ 
Χ 
Χ 
Χ 


 
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1 If total disappearance of all warts is achieved within all treated areas at visits 2, 3, 4, or 5, respective visit will be 
considered an End of Study (EOS) visit. In the case where reduction of warts is absent or incomplete, a new 
treatment cycle will be initiated for a maximum of four cycles in total for the subject. 
2 Test may not be repeated if the subject has negative HIV test results within 4 weeks before baseline. Copy of the 
test result needs to be filed with the study records. 
3 If required by applicable local regulations. 
4 Histological confirmation will be obtained if there is any doubt of the diagnosis. 
4 STUDY OBJECTIVE AND ENDPOINTS 
4.1 Study Objectives 
The primary objective of this study is: 
• 
To compare the clinical efficacy of anogenital warts treatment of  patients treated with 
Podofilox Topical Gel 0.5% and patients treated with Condylox® Gel 0.5% to patients 
treated with placebo (superiority comparisons), and to compare efficacy of Podofilox 
Topical Gel 0.5% with that of Condylox® Gel 0.5% (bioequivalence comparison). 
The secondary objective of this study is: 
• 
To demonstrate safety of Podofilox Topical Gel 0.5% compared to Condylox® Gel 0.5% or 
placebo assessed by the frequency and severity of adverse events and application site 
reaction scores (erythema, dryness, burning/stinging, erosion, edema, pain, itching and 
bleeding). 
4.2 Study Endpoints 
4.2.1 Primary Endpoint 
The primary endpoint is the proportion of subjects who achieve complete cure within the 
follow up period. The proportion of subjects with complete cure for Podofilox Topical Gel 
0.5% will be compared with that of Condylox® Gel 0.5% using an equivalence analysis. For 
superiority analysis, each active treatment will be compared with Placebo. 
4.2.2 Secondary (Safety) Endpoints 
Adverse events will be summarized by frequency, by severity and will be tabulated by 
body system/organ class.  
Subject Diary Card Dispensation 
 
Χ 
Χ 
Χ 
Χ 
 
Histological Confirmation of 
Diagnosis4 
Χ 
 
 
 
 
 


 
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Local application site reactions scores (erythema, dryness, burning/stinging, erosion, 
edema, pain, itching and bleeding) in each group during the study drug application period 
will be summarized by type of reaction and by intensity score. 
5 STUDY DESIGN 
5.1 Summary of Study Design 
This is a multicenter, parallel group, randomized, double-blind, placebo-controlled trial with 
clinical endpoint comparing Podofilox Topical Gel 0.5% to Condylox® Gel 0.5% and a 
matching placebo. The study will be conducted among adult male and female patients with 
external anogenital warts.  
On the following day after the Baseline visit (Day 1) the subject will apply the study drug on 
EAWs following the recommendations given during training at the clinic site. The treatment 
phase will consist of four weekly treatment cycles at a maximum, during which the drug will 
be applied twice a day (in the morning and at the bedtime) for 3 consecutive days, then 
discontinuing for 4 consecutive days. Study drug will thus be applied only on Days 1, 2, 3, 8, 
9, 10, 15, 16, 17, 22, 23 and 24. 
Study visits will occur on the seventh (7) day of each treatment cycle: on Day 7 (Week 1), Day 
14 (Week 2), Day 21 (Week 3), and Day 28 (Week 4). Primary endpoint (total disappearance 
of all treated warts) will be evaluated during each of these visits. In case the primary endpoint 
is reached at any of the visits prior to the Day 28 visit, it will be considered the End of Study 
(EOS) visit – the Investigator will perform physical examination and repeat urine pregnancy 
test, and subject’s participation will be considered complete. If total disappearance of warts is 
not achieved, a new treatment cycle will be initiated for a maximum of four cycles in total for 
the subject. 
During each study visit, the Investigator will collect vital signs, evaluate EAWs for absence or 
presence, capturing the count of EAWs, record Local Application Site Reactions and adverse 
events (AEs), assess Patient’s Diary Card completion and subject’s compliance with the study 
drug application, review concomitant medication and confirm that there were no prohibited 
therapies applied since the last visit.  
In the event the primary endpoint (total disappearance of all warts within all treated areas) has 
been achieved prior to the Day 28 visit, this visit will be considered End of Study (EOS) visit. 
In case a subject discontinues prematurely, the Investigator will conduct an Early Termination 
(ET) visit, capturing the reason for discontinuation and performing assessments of EOS visit. 


 
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5.2 Definition of Study Drugs 
• 
Arm 1 (Test product): Subjects in this arm will receive test formulation of Podofilox Topical 
Gel 0.5% (Hyloris Developments SA). 
• 
Arm 2 (Reference Listed Drug [RLD]): Subjects in this arm will receive RLD Condylox® 
Gel 0.5% (Allergan Pharmaceuticals). 
• 
Arm 3 (Placebo): Subjects in this arm will receive a vehicle that matches the test product, 
except for the inclusion of the active ingredient (Hyloris Developments SA). 
5.3 Sample Size Considerations 
Approximately 413 subjects (177 in each active arm and 59 in placebo group) will be enrolled to 
obtain at least 392 mITT subjects (168 in each active treatment arm and 56 in placebo group) and 
to complete 350 PP subjects (150 in each active arm and 50 in placebo group). This sample size 
was calculated assuming that both active treatments would have equivalent success rates of 40% 
and placebo would have a success rate of 15%. This sample size will provide an overall probability 
of at least 0.9 of having the 90% Wald confidence interval, with Yates’ continuity correction, of 
the difference between the test and reference success rates contained within the interval -0.20 to 
+0.20 in the PP population, in addition to establishing that the success rates for both active 
treatments are statistically greater than that of the placebo arm (two-sided continuity-corrected Z-
tests, α = 0.05) in the mITT population. 
*) Superiority analysis based on two-sided, α = 0.05, continuity-corrected Z-tests. 
**) Bioequivalence (BE) analysis based on 90% confidence interval (CI) of the difference between 
Test and reference for proportions of subjects with treatment success, calculated by the Wald’s 
method with Yates’ continuity correction. 
 
6 PLANNED ANALYSIS 
The analysis planned in the SAP will be performed after the database lock. The Efficacy 
Analyses will be conducted as follow: 
mITT             
(T:R:Placebo) 
Prob. of Superiority* 
PP                
(T:R:Placebo) 
Prob. of BE** 
Prob. of study 
success 
168:168:56   (392) 
0.98 
150:150:50 (350) 
0.92 
0.90 


 
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• Superiority to placebo: "treatment success” rate occurring at four days (± 5 days) after the last 
day of the last cycle of treatment using the mITT study population (PP population considered as 
supportive) and LOCF.  
• 
BE: “treatment success” rate between the test product and RLD treatment groups occurring at four 
days (± 5 days) after the last day of the last cycle of treatment must be within [-0.20, +0.20] for the 
dichotomous primary endpoint, using the PP study population (mITT population considered as 
supportive). 
Due to GCP non-compliance of site 201, Sponsor decided to generate two sets of Efficacy 
Analysis:  
• a Definitive Efficacy Analysis Set excluding site 201 and  
• a Supplemental Efficacy Analysis Set including site 201.  
Please see corresponding Note to File (NTF) dated 27 Feb 2019 in study documentation 
detailing the specifics of the GCP non-compliance of site 201. 
 
7 GENERAL CONSIDERATION FOR DATA ANALYSIS AND 
HANDLING 
7.1 General Summary Table and Individual Subject Data Listing 
Summary tables and listings (e.g., post text tables and individual subject data listings are 
prepared according to ICH Guideline E3) include a “footer” providing explanatory notes that 
indicate as a minimum: 
1. SAS program name. 
2. Programmer initials. 
3. Date of data extraction. 
4. Date of output generation. 
Post text tables also include reference(s) to the subject data listing(s) that supports the summary 
data. The data extraction date links the output to the archived database that is locked to ensure 
the replication of the results. 
Post text tables will be organized with respect to treatment group and a column will be included 
to summarize all treated subjects. The order of drug presentation will be investigational drug 


 
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first followed by the reference drug, then the placebo, then the vehicle control. A total column 
will appear as the last column. The summary tables clearly indicate the number of subjects to 
which the data apply and unknown or not performed are distinguished from missing data. 
Summary tables for medications and medical conditions are coded according the WHO Drug 
Dictionary. Adverse event preferred terms and body/organ systems are coded using the 
MedDRA dictionary. The MedDRA dictionary can be used, as well, in the coding of signs and 
symptoms, medical history, physical examination abnormalities, and clinical diagnoses. 
Supportive individual subject data listings, as a minimum, are sorted and presented by treatment 
group and subject ID. Listings also include visit number, visit date, and days relative to the 
initiation of double-blind treatment. 
7.2 General Summary Table and Individual Subject Data Listing Considerations 
The default convention is to number tables and listings using a decimal system to reflect main 
levels of unique tables and listings and sub-levels of replicate tables and listings with two digits 
per level (e.g., Table XX.YY.ZZ. …). 
1. The first level number should be consistent with the corresponding CSR appendix in which 
the tables or listings will appear. For example, the post text tables usually occupy Appendix 
14 and the individual subject data listings are put in Appendix 16. All post text tables should 
have a main number level 14 and listings 16. The subject accounting and disposition table is 
usually first in the first section of the report and should be numbered Table 14.1. The 
supportive subject data listing would be Listing 16.1. A subset by sex 2. Subject accounting 
and final disposition should appear as the second level number (Table 14.1 series). Baseline 
and demographic profile occupy the next sub-level (Table 14.1.2 series). Efficacy should 
come next (Table 14.3 series) followed by safety (Table 14.4 series). Reasons for subjects’ 
being excluded from efficacy and protocol violation summary tables should appear as the 
last level (Table 14.5 series). Similar conventions should be applied to the subject data 
listings. 
3. The title should be complete, accurate, and concise. The last line of the title should provide 
the analysis group being summarized (e.g., Intent-to-Treat Subjects or Per-Protocol Efficacy 
Subjects). If possible, the units of measurement for data contained in the table can appear in 
parentheses to conserve space in the body of the table. For example, the summary of vital 
signs title could read “Summary of Sitting and Standing Blood Pressure (mmHg) and Heart 
Rate (bpm).” Whether in the title or body of a table or listing, units must always be specified 
for all appropriate data. 


 
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4. If possible, variables being summarized and statistics reported should appear in the left most 
column of a table. The next columns for treatment groups should report the data from left to 
right for the investigational drug, comparative agents, placebo, and all treated subjects, 
respectively. 
In general, the listings should be sorted and presented by treatment assignment, investigational 
site, and subject number. Treatment assignment and site can appear in the banner of the listing. 
From left to right, the subject number, visit number, visit date, and relative day should appear. 
All tables and listings must have explanatory notes that give, as a minimum, data extraction 
date, output generation date, complete program name and path where it is stored, CRF pages 
from which the data were obtained, and supportive listings or tables supported, as appropriate. 
The definition of all derived variables and decodes for coded data must appear in the notes. Due 
to space limitations, tables and listings may require a page of notes as a one-time preface to the 
output. 
7.3 Data Management 
Biorasi will create SDTM data sets and ADaM analysis data sets using (SAS®) software. Data 
analyses and summary tables wil be generated using SAS version 9.4 or above. 
7.4 Data Presentation Conventions 
Continuous variables (e.g. age) are summarized using descriptive statistics (number of subjects 
with available data, mean, standard deviation (SD), coefficient of variation (CV), median, 
minimum and maximum). Categorical variables (e.g. race) are summarized using counts and 
percentages. Percentages are calculated using the total subjects per treatment group. 
The following conventions are applied to all data presentations and summaries. 
For continuous variables, all mean, median, and coefficient of variation values are formatted to 
one more decimal place than the measured value. Standard deviation values are formatted to 
two more decimal places than the measured value. Minimum and maximum values are 
presented with the same number of decimal places as the measured value. 
For categorical variables, the number and percentage of responses are presented in the form XX 
(XX.X %) where the percentage is in the parentheses.  
Date variables are formatted as DDMMMYYYY for presentation. Time is formatted in military 
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Wherever possible, data will be decimal aligned. 
P-values, if applicable, will be presented to 4 decimal places. If the p-value is less than 0.0001 
then it will be presented as <0.0001. 
Unless otherwise stated, any statistical tests performed will be 2-sided at the 5% significance 
level. 
The table and listing shells and table of contents as part of this SAP provide the expected layout 
and titles of the tables, listings and figures. Any changes to format, layout, titles, numbering, or 
any other minor deviation will not necessitate a revision to the SAP nor will it be considered a 
deviation from planned analyses. Only true differences in the analysis methods or data handling 
will necessitate such documentation. The appropriate listings supporting the tables will be 
included and are not specified in the individual sections throughout the document. 
7.5 Analysis Populations 
7.5.1 Definitive and Supplemetal  
Due to GCP non-compliance at site 201, it was decided to exclude data from that site from 
the Definitive Efficacy Analysis. A Supplemental Efficay Analysis will be presented 
including the data from site 201. 
The mITT and PP populations defined below will not inlcude site 201. However,  there will 
be  a supplemental mITT population (mITTs) and a supplemental PP population (PPs), both 
of which will include site 201. 
7.5.2 Screen Failures 
Investigators must account for all subjects who sign informed consent and will maintain an 
Enrollment Log capturing subjects screened and indicating who was enrolled or excluded 
and the reason why. If the subject is found not to be eligible prior to enrollment, the reason(s) 
for ineligibility must be documented by the Investigator. 
These subjects will neither contribute to data presentations nor be included in formal 
statistical analyses. The number of screen failures will be included in the data disposition 
table. Subject Numbers assigned to subjects who fail Screening will not be re-used. 


 
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7.5.3 Protocol Deviations 
A deviation is defined as an “unintentional and/or accidental change to, or non-adherence 
to, the IRB/EC approved trial protocol (Biorasi SOP CL-035).” Protocol deviations will be 
documented for randomized subjects as well as screen failures in this trial.  
• Minor Protocol Deviation - defined as any change, divergence, or departure from 
the IRB/IEC Approved Trial Protocol, criteria or procedures that does not affect the 
Subject's safety, rights, or welfare and/or the integrity of the Trial and its resultant 
data.  
• Major Protocol Deviation - defined as any change, divergence, or departure from the 
IRB/IEC Approved Trial Protocol, criteria or procedures that may affect the 
Subject's safety, rights, or welfare and/or integrity of the Trial and its resultant data.  
Prior to database lock, there will be a joint classification meeting held between the Sponsor, 
Data Management, Biostatistics, and Clinical in order to classify protocol deviations and 
patient classification. This information will be added to the PVPD log and utilized for setting 
the population flags for analysis. 
Any subject adjudication to the PP population and mITT population should be supported by 
Data Management according to protocol and take into consideration the PVPD log provided 
by Principal Investigators. Subjects who experience a Major Deviation will be excluded 
from the PP population. 
7.5.4 Safety Population 
The safety population includes all randomized subjects who received and used study 
product. 
7.5.5 Modified Intent-to-Treat (mITT) Population 
The modified intent-to-treat population (mITT) includes all subjects who are randomized, 
applied at least one dose of assigned product, and returned for at least one post-baseline 
evaluation visit. Subjects discontinued prematurely from the study for any reason other than 
Treatment Failure, (i.e., noncompliance, withdrawal of consent, etc.) will be included in the 
mITT population, using Last Observation Carried Forward (LOCF). 
7.5.6 Per-Protocol (PP) Population 
All randomized subjects who met all inclusion/exclusion criteria, had no protocol violations 
that would affect the treatment evaluation , were compliant with applying study product, 
and returned to the study site for the primary endpoint evaluation at 4 days (± 5 days) after 
the last day of the last cycle of treatment. Compliant subjects are defined as those who used 


 
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at least 75% and no more than 125% of study drug doses until treatment success or four 
cycles of treatment. 
Subjects discontinuing due to “treatment failure” will be included in the PP population 
analysis as Treatment Failures and will have alternative treatment recommended by the 
Investigator.  
The results in the PP population will be considered definitive for therapeutic equivalence 
and those in the mITT population considered supportive. The results in the mITT population 
will be considered definitive for superiority analysis of each active treatment to placebo and 
those in the PP population will be considered supportive. Safety analyses will be performed 
using the Safety population. 
7.6 Baseline Definition 
The Baseline visit (Day 0) will take place once the results of Screening assessments are 
obtained, suggesting that the subject is eligible for entering the study. During this visit, those 
subjects who qualify for entering the study will be randomized to one of the study arms in a 
ratio of 3:3:1. 
Derived and Transformed Data. 
7.6.1 Baseline Age 
Subject’s age in years will be calculated based on the date of the Baseline Visit date using 
the following formula: 
Age (years) = FLOOR( (INTCK('month', Date of Birth, Date of Baseline Visit) - 
(DAY(Date of Baseline Visit) < MIN(DAY(Date of Birth), DAY (INTNX ('month', Date 
of Baseline Visit, 1) - ) ) ) /12 )17 where: 
• FLOOR( ) is a SAS function that returns the largest integer that is less than or equal to the 
argument. 
• INTCK() is a SAS function that returns the number of interval boundaries of a given kind 
that lie between two dates, times, or datetime values. 
• DAY() is a SAS function that returns the day of the month from a SAS date value. 
• INTNX() is a SAS function that increments a date, time, or datetime value by a given time 
interval, and returns a date, time, or datetime value. 


 
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7.6.2 Study Day  
• Day 1 is defined as the day after the baseline when the subject will receive the first dose. 
• For a visit date on or after the date of the first dose: Study Day = (date of interest – date of 
first dose) + 1 
• For a visit date before the date of the first dose: Study Day = (date of interest – date of first 
dose) 
7.6.3 Visit Windows 
 Visit windows for study 016-POD-001 are as follows: 
Study Phase 
Visit 
Visit Name 
Day 
Screening 
Visit 1 
Screening  
-14 to -1 days 
Baseline 
Visit 2 
Baseline  
Day 0 
Follow-up 
Visit 3 
1st Follow-up Visit (FU 1) 
Day 7 (±1) 
Visit 4  
2nd Follow-up Visit (FU 2) 
Day 14 (±1) 
Visit 5 
3rd Follow-up Visit (FU 2) 
Day 21 (±1) 
Visit 6 
End of Study 
Day 28 (±5) 
End of Study1 
EOS 
End of Study  
Day1 – Day 28 (+5) 
 
ET 
Early Termination Visit 
From Screening to 
Day 28 
 
US 
Unscheduled Visit  
From Screening to 
Day 28 (+5) 
1. If total disappearance of all warts is achieved within all treated areas at visits 2, 3, 4, or 5, respective 
visit will be considered an End of Study (EOS) visit. 
 
 
 


 
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The flowchart for the study is as follows: 
 
7.6.4 Multiple Assessments 
No multiple assessments for same visit are scheduled. 
7.6.5 Handling of Missing Data 
No data will be imputed for the Safety population. Missing Data for Efficacy analyses will 
not be imputed for the PP population. However, if data is missing due to other than early 
termination because of treatment failure, it will be imputed as LOCF for the mITT 
population. 
7.6.6 Missing Start and Stop Dates for Prior and Concomitant Medication 
Start date: 
1. If start date is completely missing, start date will not be imputed. 
2. If (year is present and month and day are missing) or (year and day are present and month 
is missing), set month and day to January 1. 
3. If year and month are present and day is missing, set day to the 1st day of month. 
Stop date: 
1. If end date is completely missing, end date will not be imputed. 
2. If (year is present and month and day are missing) or (year and day are present and month 
is missing), set month and day to December 31st. 
3. If year and month are present and day is missing, set day to the last day of month. 
7.6.7 Missing Start and Stop Dates for Adverse Events 
Start date: 
1. If start date is completely missing, start date is set to date of first dose. 


 
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2. If (year is present and month and day are missing) or (year and day are present and 
month is missing): 
a. If year = year of first dose, then set month and day to month and day of first dose. 
b. If year < year of first dose, then set month and day to December 31st. 
c. If year > year of first dose, then set month and day to January 1st. 
3. If month and year are present and day is missing: 
a. If year = year of first dose and 
i. If month = month of first dose, then set day to day of first dose date. 
ii. If month < month of first dose, then set day to last day of month. 
iii. If month > month of first dose, then set day to 1st day of month. 
b. If year < year of first dose, then set day to last day of month. 
c. If year > year of first dose, then set day to 1st day of month. 
Stop date: 
If the outcome of the AE was ongoing or unknown, then the rules outlined below will not 
be applied. 
1. If stop date is completely missing, stop date is set to date of study discontinuation. 
2. If (year is present and month and day are missing) or (year and day are present and 
month is missing): 
a. If year = year of study discontinuation, then set month and day to month and day of 
study discontinuation. 
b. If year < year of study discontinuation, then set month and day to December 31st. 
c. If year > year of study discontinuation, then set month and day to December 31st. 
3. If month and year are present and day is missing: 
a. If year = year of study discontinuation and 
i. If month = month of study discontinuation, then set day to day of study 
discontinuation date. 
ii. If month < month of study discontinuation, then set day to last day of month. 
iii. If month > month of study discontinuation, then set day to last day of month. 
b. If year < year of study discontinuation, then set day to last day of month. 
c. If year > year of study discontinuation, then set day to last day of month.  
 


 
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8 STUDY POPULATION 
8.1 Subject Disposition 
The subject disposition summary will include the number screened, the number of screen 
failures, the number enrolled, the number in each patient population for analysis, the number 
who completed the study, the number who discontinued the study and reason for discontinuation 
from the study. Disposition data will be summarized by treatment and overall. 
A by-subject data listing of study completion information including the reason for study 
discontinuation will be presented. A by-subject listing of inclusion/exclusion criteria not met 
will also be presented. 
8.2 Protocol Deviations 
A summary of all protocol deviations by type will be generated. Protocol deviation data will be 
summarized by treatment and overall. A by-subject data listing of protocol deviations will also 
be presented. 
Any subject adjudication to the PP population and mITT population should be supported by 
Data Management according to protocol and take into consideration the PVPD log provided by 
Principal Investigators. 
8.3 Demographic and Baseline Characteristics 
Descriptive statistics will be generated by treatment group for selected continuous variables. 
The number and percentage of subjects in each class of categorical demographic and baseline 
variables (e.g., gender, ethnicity, and race) will be tabulated by treatment group. Individual 
subject demographic and baseline characteristic data will be listed. 
8.4 Medical History 
A by subject data listing of medical history will be presented. 


 
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9 EFFICACY ANALYSES 
9.1 Primary Efficacy Endpoint 
The primary endpoint is the proportion of subjects with “treatment success” defined as “total 
disappearance of all warts within all treated areas.” The primary endpoint will be evaluated at 
4 days (± 5 days) after the last day of the last cycle of treatment. The results of analysis for 
bioequivalence in the PP population will be considered definitive and those in the mITT 
population as supportive. 
Due to GCP non-compliance at site 201, it was decided to exclude data from that site from the 
Definitive Efficacy Analysis. A Supplemental Primary Efficay Analysis will be presented 
including the data from site 201. 
 
9.1.1   Bioequivalence Analysis 
The efficacy bioequivalence of the test and reference treatments will be based on the 
proportions of subjects with clinical success. The hypothesis tested for clinical equivalence 
between test and reference will be:  
Bioequivalence between the test and the reference product will be established if the 90% 
confidence interval for the difference in success proportions is contained within the 
equivalence limits [-0.20, +0.20]. 
In this case, the compound hypothesis to be tested is: 
𝐻𝐻0: 𝑃𝑃𝑇𝑇−𝑃𝑃𝑅𝑅 < −0.2  𝑜𝑜𝑜𝑜  𝑃𝑃𝑇𝑇−𝑃𝑃𝑅𝑅 >  0.2    (meaning test product is not bioequivalent to 
the reference); 
versus 
𝐻𝐻𝑎𝑎: −0.2 ≤𝑃𝑃𝑇𝑇−𝑃𝑃𝑅𝑅 ≤ 0.2   (supporting bioequivalence); 
where PT = success proportion of test treatment, PR = success proportion of reference 
treatment.  
Let  
1. nT = sample size of test treatment group 
2. cnT = number of subjects with success in test treatment group 
3. nR = sample size of reference treatment group 
4. cnR = number of subjects with success in reference treatment group 
𝑃𝑃෠𝑇𝑇= 𝑐𝑐𝑐𝑐𝑇𝑇𝑛𝑛𝑇𝑇
ൗ
 ,   𝑃𝑃෠𝑅𝑅= 𝑐𝑐𝑐𝑐𝑅𝑅𝑛𝑛𝑅𝑅
ൗ
 ,  


 
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and 𝑠𝑠𝑠𝑠= ቆ𝑃𝑃෠𝑅𝑅൫1 −𝑃𝑃𝑅𝑅
෢൯
𝑛𝑛𝑅𝑅
൘
+ 𝑃𝑃෠𝑇𝑇൫1 −𝑃𝑃𝑇𝑇
෢൯
𝑛𝑛𝑇𝑇
൘
ቇ
1 2
ൗ
    
The 90% confidence interval will be estimated using Wald’s method with Yates’ continuity 
correction, as: 
 
H0 will be rejected if L ≥ -0.20 and U ≤ 0.20 resulting in accepting HA and concluding 
bioequivalence of the two products. 
Tthe following SAS code will be used to test bioequivalence: 
proc freq data = dataset; 
tables treat*outcome/ riskdiff (Equiv correct); 
run; 
 
9.1.2 Superiority Analysis 
Superiority will be assessed through continuity-corrected Z-tests comparing each active 
treatment to placebo. If both the test and RLD success proportions are statistically 
significantly greater than the placebo proportion (p<0.05) then they will be considered 
superior to the placebo.  The results in the mITT population will be considered definitive 
and those in the PP population will be considered supportive. 
For each treatment (Test and RLD) the Hypothesis to be tested is: 
𝐻𝐻0: 𝑝𝑝𝑡𝑡− 𝑝𝑝𝑝𝑝 ≤ 0 
𝐻𝐻𝑎𝑎: 𝑝𝑝𝑡𝑡− 𝑝𝑝𝑝𝑝 >  0 
Where pt = Proportion of cure for Treatment, and pp is proportion of cure for Placebo. 
The rest of the formulation is the similar to the one for Equivalence assessment, using 95% 
Confidence Interval. For testing the superiority, the following SAS code will be used: 
proc freq data = dataset; 


 
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tables treat*outcome/ riskdiff (Equal correct); 
run; 
 
10 SAFETY ANALYSES 
10.1 Safety Endpoints 
The reporting of safety data is descriptive, and it will include all subjects who receive at 
least one dose of investigational product. The variables for safety endpoints are AEs, Local 
Application Site Reactions and vital signs measurements. Safety data will be summarized 
by treatment group and time point of collection, when appropriate. 
Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHO-DD). These data will be summarized by treatment group. Previous and 
concomitant medications will be presented in a data listing. 
10.1.1 Adverse Events 
Adverse events will be coded using the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA) and will be summarized based on frequency and severity 
of AEs for all treated subjects. Data will be summarized using preferred term and system 
organ classifications. Summary will show number and percentage of subjects who 
experience each AE. 
If a subject experiences multiple events that map to a single preferred term, the greatest 
severity and strongest Investigator assessment of relation to study drug will be assigned to 
the preferred term for the appropriate summaries. Should an event have a missing severity 
or relationship, it will be classified as having the highest severity and/or strongest 
relationship to study drug. 
Summaries of treatment-emergent AEs will include any AEs reported beginning with the 
first dose of study drug on Day 1. The occurrence of treatment-emergent adverse events will 
be summarized by treatment group using preferred terms, system organ classifications, and 
severity. Separate summaries of treatment-emergent serious adverse events, treatment-
emergent adverse events related to study drug, and events leading to the discontinuation of 
study drug will be generated. All adverse events reported will be listed for individual 
subjects showing both verbatim and preferred terms. 
 


 
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10.1.2 Local Application Site Reactions  
Local Application Site Reactions will be recorded at each study visit and will be 
summarized by the type of reaction (erythema, dryness, burning/stinging, erosion, edema, 
pain, itching and bleeding) and intensity score: 0=absent, 1=mild (slight, barely 
perceptible), 2=moderate (distinct presence), 3=severe (marked, intense The number and 
percentage of subjects affected will also be presented. 
 
10.1.3 Vital Signs 
Vital Signs will be examined at several visits as per schedule on Section 3.2 above and will 
be summarized by visit and by treatment group. 
 
 


 
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11 REFERNCES 
1 Protocol Number 016-POD-001. Version 1.0 “A Multicenter, Randomized, Double-Blind, 
Parallel Group, Placebo-Controlled Study of Hyloris Development’s Podofilox Topical Gel 
0.5% compared to Allergan’s Condylox® Gel 0.5%, and Both Active Treatments to a 
Vehicle Control in male and female patients with external anogenital warts”. 
2 Wang, Wei. (1988, October 28). Calculating Age in One Line of Code. Paper presented at 
annual meeting of Northeast SAS Users Group, New York, New York. Paper retrieved from 
http://www.lexjansen.com/nesug/nesug01/cc/cc4022.pdf. 
3 Kim, Yeonhee and Won, Seunghyun. (2013, May 15). Adjusted Proportion Difference and 
Confidence Interval in Stratified Randomized Trials. Paper presented at annual meeting of 
Pharma SAS Users Group, Chicago, Illinois. Paper retrieved from 
http://www.pharmasug.org/proceedings/2013/SP/PharmaSUG-2013-SP04.pdf. 
4 Oracle. (2016, February 22). Oracle Health Sciences Empirica Study - Data sheet | Oracle 
[PDF]. 
Redwood 
City, 
CA: 
Oracle. 
http://www.oracle.com/us/industries/lifesciences/empirica-study-on-demand-ds-
396095.pdf. 
5 Oracle. (2016, March 22). Clinical Significance Criteria. Retrieved January 26, 2018, form 
https://docs.oracle.com/health-sciences/empirica-study-
80/WEWUG/Clinical_Significance_Criteria.htm.   
 
 


 
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12 APPENDIX 
12.1 APPENDIX A. Tables and Listings 
12.1.1 List of Tables 
Display Number Title 
Population 
Unique/Repeat 
Study 
Population 
 
 
 
Table 14.1.1.1.1 Subject Disposition 
All Subjects 
Unique 
Table 
14.1.1.1.2.1 
Subject Enrollment and Disposition 
All Subjects 
Unique 
Table 
14.1.1.1.2.2 
Subject Enrollment and Disposition, 
Supplemental (including site 201) 
All Subjects 
Repeat 
Table 14.1.1.1.3 Subject Disposition by Site and Treatment 
All Subjects 
Unique 
Table 14.1.1.2 
Randomized Subjects Not Included in Safety, 
PP, and mITT Populations by Treatment 
 
All Subjects 
Unique 
Table 14.1.2.1 
Summary of Protocol Deviations by 
Classification and Category  
Safety 
Population 
Unique 
Table 14.1.2.2 
Summary of Protocol Deviations by 
Classification and Category Supplemental 
(including site 201) 
Safety 
Population 
Repeat 
Table 14.1.3.1.1 Summary of Demographic  
mITT 
Unique 
Table 14.1.3.1.2 Summary of Demographic  
PP 
Repeat 
Table 14.1.3.1.3 Summary of Demographic 
Safety 
Repeat 
Efficacy Tables  
 
 
Table 14.2.1.1.1 Summary of Treatment Success by Visit 
PP 
Unique 
Table 14.2.1.1.2 Summary of Treatment Success by Visit, 
Supplemental (including site 201) 
PPs 
Repeat 
Table 14.2.1.2.1 Summary of Treatment Success by Visit 
mITT 
Repeat 
Table 14.2.1.2.2 Summary of Treatment Success by Visit, 
Supplemental (including site 201) 
mITTs 
Repeat 
Table 14.2.2.1.1 Treatment Success, Bioequivalence Test 
between Test Product and Reference 
PP/mITT 
Unique 


 
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Display Number Title 
Population 
Unique/Repeat 
Table 14.2.2.1.2 Treatment Success, Bioequivalence Test 
between Test Product and Reference, 
Supplemental (including site 201) 
PPs/mITTs 
Repeat 
Table 14.2.3.1.1 Treatment Success, Superiority Test from 
Placebo 
mITT/PP 
Unique 
Table 14.2.3.1.2 Treatment Success, Superiority Test from 
Placebo, Supplemental (including site 201) 
mITTs/PPs 
Repeat 
Table 14.2.4.1.1 Number of Genital Warts by Visit 
PP 
Unique 
Table 14.2.4.1.2 Number of Genital Warts by Visit, 
Supplemental (including site 201) 
PPs 
Repeat 
Table 14.2.4.2.1 Number of Genital Warts by Visit 
mITT 
Repeat 
Table 14.2.4.2.2 Number of Genital Warts by Visit, 
Supplemental (including site 201) 
mITTs 
Repeat 
Table 14.2.5.1.1 Number of Perianal Warts by Visit 
PP 
Unique 
Table 14.2.5.1.2 Number of Perianal Warts by Visit, 
Supplemental (including site 201) 
PPs 
Repeat 
Table 14.2.5.2.1 Number of Perianal Warts by Visit 
mITT 
Repeat 
Table 14.2.5.2.2 Number of Perianal Warts by Visit, 
Supplemental (including site 201) 
mITTs 
Repeat 
Table 14.2.6.1.1 Number of Genital and Perianal Warts by 
Visit 
PP 
Unique 
Table 14.2.6.1.2 Number of Genital and Perianal Warts by 
Visit, Supplemental (including site 201) 
PPs 
Repeat 
Table 14.2.6.2.1 Number of Genital and Perianal Warts by 
Visit 
mITT 
Repeat 
Table 14.2.6.2.2 Number of Genital and Perianal Warts by 
Visit, Supplemental (including site 201) 
mITTs 
Repeat 
Table 14.2.7.1.1 Warts Area (cm2) by Visit 
PP 
Unique 
Table 14.2.7.1.2 Warts Area (cm2) by Visit, Supplemental 
(including site 201) 
PPs 
Repeat 
Table 14.2.7.2.1 Warts Area (cm2) by Visit 
mITT 
Repeat 
Table 14.2.7.2.2 Warts Area (cm2) by Visit, Supplemental 
(including site 201) 
mITTs 
Repeat 
Safety 
 
 
 
Table 14.3.1.1 
Summary of Vital Sign  
Safety  
Unique 


 
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Display Number Title 
Population 
Unique/Repeat 
Table 14.3.1.2 
Vital Signs Changes from Baseline 
Safety 
Unique 
Table 14.3.2 
Summary of Physical Examination 
Safety 
Unique 
Table 14.3.3 
Summary of Study Drug Exposure, Dose in 
grams by Week 
Safety 
Unique 
Table 14.3.4.1 
Summary of Study Drug Exposure, Number 
of Applications by Week 
Safety 
Unique 
Table 14.3.4.2 
Summary of Study Drug Exposure, Duration 
of Exposure in Hours by Week 
Safety 
Unique 
Table 14.3.5 
Summary of Treatment Compliance (%) by 
Week 
Safety 
Unique 
Table 14.3.6 
Summary of Concomitant Medications by 
Preferred Term 
Safety 
Repeat 
Table 14.3.7 
Summary of Site Reaction by Intensity and 
Visit 
Safety 
Unique 
Table 14.3.8 
Overall Summary of Adverse Events 
Safety 
Unique 
Table 14.3.8.1.1 Summary of Treatment Emergent Adverse 
Events (TEAEs) by System Organ Class and 
Preferred Term 
Safety 
Unique 
Table 14.3.8.1.2 Summary of Treatment Emergent Adverse 
Events (TEAEs) by System Organ Class, 
Preferred Term, and Severity 
Safety 
Unique 
Table 14.3.8.1.3 Summary of Treatment Emergent Adverse 
Events (TEAEs) by System Organ Class, 
Preferred Term, and Causality 
Safety 
Repeat 
Table 14.3.8.2 
Summary of Treatment Emergent Serious 
Adverse Events (TESAEs) by System Organ 
Class and Preferred Term 
Safety 
Unique 
 


 
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Table 14.1.1.1.1 
Subject Disposition, All Subjects 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
Listing: 16.1.1.1 
Snapshot Data: DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
Population 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
All Subjects 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Safety Population 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
mITT Population 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
PP Population 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
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Table 14.1.1.1.2.1 
Subject Enrollment and Disposition, All Subjects 
Disposition 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
Screened 
 
 
 
xx (xx.x) 
Randomized 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Treated 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Completed Study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Completed Day 0 (Baseline) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Completed Day 7 (Visit 3) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Completed Day 14 (Visit 4) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Completed Day 21 (Visit 5) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Completed Day 28 (Visit 6) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Discontinued 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Screen Failure 
 
 
 
xx (xx.x) 
Withdrawal of consent by subject  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Withdrawal of subject by Investigator’s Decision 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Pregnancy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Occurrence of an Adverse Event (AE) or Serious 
Adverse Event (SAE) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Significant non-compliance with study 
procedures  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Treatment failure 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
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Disposition 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
Subject's medication code unblinded 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Subject no longer meets the entry criteria 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Lost of follow-up 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Investigator discretion 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
Source: <Dataset> 
Listing: 16.1.1.1 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
Repeat as Supplemental Analysis including site 201 


 
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Table 14.1.1.1.3 
Subject Disposition by Site and Treatment, All Subjects 
Site 
Disposition 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
101 
Screened 
 
 
 
xx (xx.x) 
 
Screen failure 
 
 
 
xx (xx.x) 
 
Randomized 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Treated 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Completed 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Discontinued 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Repeat for each site 
 
 
 
 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
Source: <Dataset> 
Listing: 16.1.1.1 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Table 14.1.1.2 
Randomized Subjects Not Included in Safety, PP, and mITT Populations by Treatment, All Subjects 
 
Statistic 
Test Product 
 Reference 
Placebo 
All Subjects 
Randomized 
N 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
Total Safety Population 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Total exclusion from Safety population 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Reason for exclusion from Safety 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          No record of first dose 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Total mITT Population 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Total exclusion from mITT population 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Reason for exclusion from mITT 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          No record of first dose 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          No post-treatment data 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          [add additional items] 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Total PP Population 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Total exclusion from PP population 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Reason for exclusion from PP 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          Enrolled in error 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          Lost to follow-up 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          Non-compliant (dosing) 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          Outside visit window 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          Randomized in error 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          Restricted medication 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
          [add additional items] 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
Source: <Dataset> 
Listing: 16.1.1.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
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Table 14.1.2.2 
Summary of Protocol Deviations by Classification and Category,  
Safety Population 
Classification/Category 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
Number of patients with: 
 
 
 
 
At least one Major Deviation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At least one Minor Deviation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Major Deviations 
xx  
xx  
xx  
xx  
Subject Dosing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Inclusion/Exclusion criteria 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
[add additional items] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Minor Deviations 
xx  
xx  
xx  
xx  
Out of window 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
[add additional items] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
n: Number of deviations, except for the two first lines where it is specified as number of patients. 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
Source: <Dataset> 
Listing: 16.1.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Table 14.1.3.1.1 
Summary of Demographics, mITT Population 
Variable 
Statistic 
Test Product 
N = 
Reference 
N= 
Placebo 
N= 
All Subjects 
N = 
Age 
N 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Sex 
n 
 
 
 
 
Male 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Female 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Ethnicity 
n (%) 
 
 
 
 
Hispanic or Latino  
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Hispanic or Latino 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Race 
n (%) 
 
 
 
 
American Indian or Alaskan         
Native 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Asian 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Black or African American  
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Native Hawaiian or Other 
Pacific Islander 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
White 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Other 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Repeat for PP and Safety populations 
Source: <Dataset> 
Listing: 16.1.3.1 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 45 of 87 
Table 14.2.1.1.1 
Summary of Treatment Success by Visit, PP Population 
Visit 
Test Product 
N = 
n (%) 
Reference 
N = 
n (%) 
Placebo 
N = 
n (%) 
All Subjects 
N = 
n (%) 
Visit 3 (Day 7) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
Visit 4 (Day 14) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
Visit 5 (Day 21) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
Visit 6 (Day 28) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
EOS 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
Treatment success: total disappearance of all warts within all treated areas. 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Repeat for mITT population, and as Supplemental Analysis including site 201 for PPs and mITTs 
 
 
Source: <Dataset> 
Listing: 16.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 46 of 87 
Table 14.2.2.1.1 
Bioequivalence Test for Proportion of Treatment Success between Test and Reference Products  
Population 
Test Product 
n (%) 
Reference    Difference (SE)        90% CI 
       n (%)     
PP                               EOS 
xx (xx.xx) 
  xx (xx.xx)        x.xx (x.xxx)        (x.xx, x.xx) 
          mITT 
xx (xx.xx) 
  xx (xx.xx)        x.xx (x.xxx)        (x.xx, x.xx) 
n: Number of subjects who experienced treatment success 
SE: Standard Error 
CI: Confidence Interval 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
 
Repeat as Supplemental Analysis including site 201 for PPs/mITTs 
Source: <Dataset> 
Listing: 16.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 47 of 87 
Table 14.2.3.1.1 
Treatment Success, Superiority Test from Placebo  
 
 
Test Productn 
(%) 
Reference 
n (%) 
Placebo 
n (%) 
Test vs. Placebo 
Diff (95% CI) p 
Reference vs. Placebo- 
Diff (95% CI)  
 
mITT                    
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
x.xx (x.xx, x.xx) x.xxxx 
x.xx (x.xx, x.xx)  
PP 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
x.xx (x.xx, x.xx) x.xxxx 
x.xx (x.xx, x.xx)  
 
 
 
 
 
 
 
n: Number of subjects who experienced treatment success 
SE: Standard Error 
CI: Confidence Interval 
p: Probability of lower bound of CI with Walt-Yate’s continuity correction 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
 
 
 
Repeat as Supplemental Analysis including site 201 for PPs/mITTs 
Source: <Dataset> 
Listing: 16.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD THH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 48 of 87 
Table 14.2.4.1.1 
Number of Genital Warts by Visit, PP Population 
Visit 
Statistic 
N = 
Test Product 
N = 
Reference 
N = 
Placebo 
N = 
All Subjects 
N = 
Baseline (Day 0) 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 (Day 7) 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 change from 
baseline 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for Visits 4, 5, 6 and EOS  
 
 
 
 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
Repeat for mITT population, and as Supplemental Analysis including site 201 for PPs and mITTs 
 
 
Source: <Dataset> 
Listing: 16.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 49 of 87 
Table 14.2.5.1.1 
Number of Perianal Warts by Visit, PP Population 
Visit 
Statistic 
Test Product 
N= 
Reference 
N= 
Placebo 
N= 
All Subjects 
N= 
Baseline (Day 0) 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 (Day 7) 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 change from 
baseline 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for Visits 4, 5, 6 and EOS.  
 
 
 
 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
Repeat for mITT population, and as Supplemental Analysis including site 201 for PPs and mITTs 
Source: <Dataset> 
Listing: 16.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 50 of 87 
Table 14.2.6.1.1 
Number of Genital and Perianal Warts by Visit, PP Population 
Visit 
Statistic 
Test Product 
N= 
Reference 
N= 
Placebo 
N= 
All Subjects 
N= 
Baseline (Day 0) 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 (Day 7) 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 change from 
baseline 
n 
n (%) 
n (%) 
n (%) 
n (%) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for Visits 4, 5, 6 and EOS.  
 
 
 
 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
Repeat for mITT population, and as Supplemental Analysis including site 201 for PPs and mITTs 
Source: <Dataset> 
Listing: 16.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 51 of 87 
Table 14.2.7.1.1 
Warts Area (cm2) by Visit, PP population 
Visit 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
Baseline (Day 0) 
n 
n 
 
 
 
 
Mean (SD)  
xx.x (xx.xx) 
 
 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max  
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 (Day 7) 
n 
 
 
 
 
 
Mean (SD)  
xx.x (xx.xx) 
 
 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max  
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Visit 3 change from 
baseline  
n 
 
 
 
 
 
Mean (SD)  
xx.x (xx.xx) 
 
 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max  
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for Visits 4, 5, 6 and EOS. 
 
 
 
 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
Repeat for mITT population, and as Supplemental Analysis including site 201 for PPs and mITTs 
 
Source: <Dataset> 
Listing: 16.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 52 of 87 
Table 14.3.1.1 
Summary of Vital Signs, Safety Population  
Visit 
Vital Sign 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
Baseline (Day 0) 
Temperature 
n 
xx 
xx 
xx 
xx 
 
(°C) 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
Heart Rate 
n 
xx 
xx 
xx 
xx 
 
(beats per  
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
minute) 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
Systolic BP 
n 
xx 
xx 
xx 
xx 
 
(mmHg) 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
Diastolic BP 
n 
xx 
xx 
xx 
xx 
 
(mmHg) 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for visits 3, 4, 5 and 6. 
 
 
 
 
 
Test Product: Podofilox Topical Gel 0.5% 
 
Reference: Condylox® Gel 0.5% 
 
Placebo: vehicle that matches the test product 
 
Source: <Dataset> 
Listing: 16.3.1 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
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Version 2.0, 15-Jan-2018 
 
 
 
  
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Page 53 of 87 
Table 14.3.1.2 
Vital Signs Changes from Baseline, Safety Population  
Visit 
Vital Sign 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
Visit 3 (Day 7) 
Temperature 
n 
xx 
xx 
xx 
xx 
 
(°C) 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
Heart Rate 
n 
xx 
xx 
xx 
xx 
 
(beats per  
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
minute) 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
Systolic BP 
n 
xx 
xx 
xx 
xx 
 
(mmHg) 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
Diastolic BP 
n 
xx 
xx 
xx 
xx 
 
(mmHg) 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for Visits 4, 5 and 6. 
 
 
 
 
 
Test Product: Podofilox Topical Gel 0.5% 
 
Reference: Condylox® Gel 0.5% 
 
Placebo: vehicle that matches the test product 
 
Source: <Dataset> 
Listing: 16.3.1 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 54 of 87 
Table 14.3.2 
Summary of Physical Examination, Safety Population  
Visit 
Physical Examination 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
Baseline (Day 0) 
Height (cm) 
n 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
Weight (kg) 
n 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
General Appearance 
 
 
 
 
 
 
Normal  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal NCS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal CS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Heart Cardiovascular 
 
 
 
 
 
 
Normal  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal NCS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal CS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Lungs 
 
 
 
 
 
 
Normal  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal NCS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal CS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Gastrointestinal 
 
 
 
 
 
 
Normal  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal NCS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal CS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 55 of 87 
Visit 
Physical Examination 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
 
Not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Ear/Nose/Throat 
 
 
 
 
 
 
Normal  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal NCS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal CS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Extremities 
 
 
 
 
 
 
Normal  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal NCS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal CS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Skin 
 
 
 
 
 
 
Normal  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal NCS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal CS 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Other 
 
 
 
 
 
Repeat for EOS, ET visit and the change from 
Baseline. 
 
 
 
 
 
NCS: Non-Clinically Significant 
CS: Clinically Significant 
 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
Listing: 16.3.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 56 of 87 
Table 14.3.3 
Summary of Study Drug Exposure, Dose in grams by Week, Safety Population  
Week 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
Week 1  
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
Repeat for all Weeks 
 
 
 
 
 
 
 
 
 
 
 
Weekly Average  
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
n: Number of Subjects 
Mean, SD, Median, Min, and Max in Grams. 
Test Product: Podofilox Topical Gel 0.5% 
 
Reference: Condylox® Gel 0.5% 
 
 
Placebo: vehicle that matches the test product 
 
 
 
Source: <Dataset> 
Listing: 16.3.3 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 57 of 87 
Table 14.3.4.1 
Summary of Study Drug Exposure, Number of Applications by Week, Safety Population 
Week 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
Week 1 
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for all Weeks 
 
 
 
 
 
 
 
 
 
 
 
Weekly Average  
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
n: Number of Subjects 
Mean, SD, Median, Min, and Max of number of applications during a week. 
Test Product: Podofilox Topical Gel 0.5% 
 
 
Reference: Condylox® Gel 0.5% 
 
 
Placebo: vehicle that matches the test product 
 
 
 
 
Source: <Dataset> 
Listing: 16.3.4 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 58 of 87 
Table 14.3.4.2 
Summary of Study Drug Exposure, Duration of Exposure in Hours by Week, Safety Population 
Week 
Statistic 
Test Product 
Reference 
Placebo 
All Subjects 
Week 1 
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for all 
Weeks 
 
 
 
 
 
 
 
 
 
 
 
Weekly Average  
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
n: Number of Subjects 
Mean, SD, Median, Min, and Max of hours from first application of the week to last application of the week.  
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
Source: <Dataset> 
Listing: 16.3.4 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 59 of 87 
Table 14.3.5 
Summary of Treatment Compliance (%) by Week, Safety Population 
Week 
Statistic 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
Week 1 
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for all 
Weeks 
 
 
 
 
 
 
 
 
 
 
 
Weekly Average  
n 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
xx.x (xx.xxx) 
 
CV 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
n: Number of Subjects 
Mean, SD, Median, Min, and Max of percentage of treatment compliance by week.  
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
Source: <Dataset> 
Listing: 16.3.5 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
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Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 60 of 87 
Table 14.3.6 
Summary of Concomitant Medications by Preferred Term, Safety Population 
WHO-DD ATC Class Level 1 
      WHO-DD ATC Class Level 2 
           WHO-DD Preferred Term 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
 
 
 
 
 
Number of subjects with at least one concomitant 
medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
WHO-DD ATC Class Level 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
      WHO-DD ATC Class Level 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
           WHO-DD Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
           WHO-DD Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
            etc. 
 
 
 
 
 
 
 
 
 
WHO-DD ATC Class Level 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
      WHO-DD ATC Class Level 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
           WHO-DD Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
           WHO-DD Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
            etc. 
 
 
 
 
Concomitant medications are coded using the World Health Organization Drug Dictionary (WHO-DD). 
Test Product: Podofilox Topical Gel 0.5% 
 
 
 
 
Reference: Condylox® Gel 0.5% 
 
 
 
 
Placebo: vehicle that matches the test product 
 
 
 
 
Source: <Dataset> 
Listing: 16.3.6 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 61 of 87 
Table 14.3.7 
Summary of Site Reaction by Intensity and Visit, Safety Population 
Site Reaction 
Visit 
Score 
Test Product 
n (%) 
Reference 
n (%) 
Placebo 
n (%) 
All Subjects 
n (%) 
Erythema 
Baseline (Day 0) 
Absent 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Present 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Visit 3(Day7) 
Absent 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Present 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Visit 3 Change 
from Baseline 
Absent 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Present 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Repeat for Site reactions: dryness, burning/stinging, erosion, edema, pain, itching, and bleeding. 
Then Repeat for visit 4, 5, 6 and EOS. 
 
 
n: number of patients affected. 
 
Test Product: Podofilox Topical Gel 0.5% 
 
Reference: Condylox® Gel 0.5% 
 
Placebo: vehicle that matches the test product 
 
Source: <Dataset> 
Listing: 16.3.7 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 62 of 87 
Table 14.3.8 
Overall Summary of Adverse Events, Safety Population 
 
Test Product 
(N=xxx) 
n (%) 
Reference  
(N=xxx) 
n (%) 
Placebo  
(N=xxx) 
n (%) 
All Subjects (N=xxx) 
n (%) 
Total number of AEs 
xx 
xx 
xx 
xx 
Total number of SAEs 
xx 
xx 
xx 
xx 
Total Number of TEAEs 
xx 
xx 
xx 
xx 
Total Number of TESAEs 
xx 
xx 
xx 
xx 
 
 
 
 
 
Number of Subjects with: 
 
 
 
 
At Least One TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One Related TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One Severe TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One TEAE Leading to 
Discontinuation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One TEAE Leading to 
Death 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One TESAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One Related TESAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One Severe TESAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
At Least One TESAE Leading to 
Discontinuation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
(S)AE: (Serious) Adverse Event reported from signature of the Informed Consent Form to 30 days following the last study drug application. 
TE(S)AE: Treatment Emerging (Serious) Adverse Event reported during the treatment period (from the day of the first application of the study 
drug and up to the last visit). 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
Listings: 16.3.8.1 – 16.3.8.2 – 16.3.8.3 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 63 of 87 
Table 14.3.8.1.1 
Summary of Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term, Safety Population 
 
Test Product 
(N=xxx) 
n (%) 
Reference 
(N=xxx) 
n (%) 
Placebo 
(N=xxx) 
n (%) 
All Subjects 
(N=xxx) 
n (%) 
Total Number of AEs 
xx 
xx 
xx 
xx 
Number of Subjects with at Least One AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of subjects with at least One AE: 
 
 
 
 
System Organ Class #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     etc. 
 
 
 
 
 
 
 
 
 
System Organ Class #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     etc. 
 
 
 
 
 
AE: Adverse Event reported from signature of the informed Consent Form to 30 days following the last study drug application. 
N (%): Number of subjects and % of subjects, except for first line where it is specified as Number of AEs. 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
Source: <Dataset> 
Listing:16.3.8.1 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
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Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 64 of 87 
Table 14.3.8.1.2 
Summary of Tretment Emergent Adverse Events (TEAEs) by System Organ Class, Preferred Term, and Severity, Safety Population 
 
Severity 
Test Product 
(N=xxx) 
n (%) 
Reference 
(N=xxx) 
n (%) 
Placebo 
(N=xxx) 
n (%) 
All Subjects 
(N=xxx) 
n (%) 
Number of Subjects with at Least One 
TEAE 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Subjects with at Least One 
TEAE: 
 
 
 
 
 
System Organ Class #1 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
       Preferred Term #1 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
       etc. 
 
 
 
 
 
TEAE: Treatment Emergent Adverse Event reported during the treatment period (from the day of the first application of the study 
drug and up to the last visit). 
n (%): Number of subjects and % of subjects, except for first line where it is specified as Number of TEAEs. 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
Listing: 16.3.8.1 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
STATISTICAL ANALYSIS PLAN  
 
Version 2.0, 15-Jan-2018 
 
 
 
  
Confidential  
 
 
 
 
 
Page 65 of 87 
Table 14.3.8.1.3 
Summary of Treatment Emergent Adverse Events (TEAEs) by System Organ Class, Preferred Term, and Causality,  
Safety Population 
 
 
Causality 
Test Product 
(N=xxx) 
n (%) 
Reference 
(N=xxx) 
n (%) 
Placebo 
(N=xxx) 
n (%) 
All Subjects 
(N=xxx) 
n (%) 
Number of Subjects 
with at Least One 
TEAE 
Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Probably Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Possibly Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Probably not Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Subjects 
with at Least One 
TEAE: 
 
 
 
 
 
System Organ Class 
#1 
Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Probably Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Possibly Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Probably not Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
       Preferred Term 
#1 
Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Probably Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Possibly Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Probably not Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not Related 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
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Page 66 of 87 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
       etc. 
 
 
 
 
 
 
 
 
TEAE: Treatment Emergent Adverse Event reported during the treatment period (from the day of the first application of the study drug and up to 
the last visit) 
n (%): Number of subjects and % of subjects, except for first line where it is specified as Number of TEAEs. 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
Source: <Dataset> 
Listings:16.3.8.1 - 16.3.8.3 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
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Page 67 of 87 
Table 14.3.8.2 
Summary of Treatment Emergent Serious Adverse Events (TESAEs) by System Organ Class and Preferred Term, Safety Population 
 
Test Product 
(N=xxx) 
n (%) 
Reference 
(N=xxx) 
n (%) 
Placebo 
(N=xxx) 
n (%) 
All Subjects 
(N=xxx) 
n (%) 
Total Number of TESAEs 
xx 
xx 
xx 
xx 
Number of Subjects with at Least One TESAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of subjects with at least One TESAE: 
 
 
 
 
System Organ Class #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     etc. 
 
 
 
 
 
 
 
 
 
System Organ Class #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Preferred Term #3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     etc. 
 
 
 
 
 
 
 
 
 
TE(S)AE: Treatment Emergent (Serious) Adverse Event reported during the treatment period (from the day of the first application of the 
study drug and up to the last visit).N (%): Number of subjects and % of subjects, except for first line where it is specified as Number of 
TESAEs. 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
Source: <Dataset> 
Listing: 16.3.8.2 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
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Confidential  
 
 
 
 
 
Page 68 of 87 
12.1.2 List of Listings 
Display Number 
Title 
Population 
Study Population 
 
 
Listing 16.1.1.1 
Subject Enrollment and 
Disposition  
All Subjects 
Listing 16.1.1.2 
Randomized Patients Not 
Included in the Safety, PP and 
mITT Populations 
Randomized Subjects 
Listing 16.1.2 
Protocol Deviations 
All Subjects 
Listing 16.1.3.1 
Subject Demographics and 
Characteristics 
All Subjects 
Listing 16.1.3.2 
Medical History 
All Subjects 
Listing 16.1.3.3 
Laboratory Results. 
All Subjects 
Listing 16.1.3.4 
Prior Medications 
Safety 
Efficacy 
 
 
Listing 16.2 
Number of Warts and Area 
All Subjects 
Safety 
 
 
Listing 16.3.1 
Vital Signs 
All Subjects 
Listing 16.3.2 
Physical Examinations 
All Subjects 
Listing 16.3.3 
Study Drug Dispensation and 
Return 
Safety 
Listing 16.3.4 
Drug Administrations 
Safety 
Listing 16.3.5 
Diary Card Dispensation and 
Return, and Treatment 
Compliance 
Safety  
Listing 16.3.6 
Concomitant Medications 
Safety 
Listing 16.3.7 
Site Reaction  
Safety 
Listing 16.3.8.1 
Adverse Events by System 
Organ Class, Preferred Term, 
Frequency and Severity 
All Subjects 
Listing 16.3.8.2 
Adverse Events by System 
Organ Class, Preferred Term, 
Seriousness, Treatment 
Unblinding and 
All Subjects 


 
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Page 69 of 87 
Discontinuation of the subject 
from the Study 
Listing 16.3.8.3 
Adverse Events by System 
Organ Class, Preferred Term, 
Causality, Action Taken with 
the Study Drug, Outcome  
All Subjects 


 
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Page 70 of 87 
Listing 16.1.1.1 
Subject Enrollment and Disposition by Study Site, All Sujects 
FU: Follow-up visit 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 6, 19-22, 23, 35-38, 39, 44, 56, 68, 79, 
104, 105, 110 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name> 
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
Site 
Patient 
ID 
Treatment 
Group 
Population 
Visit 
Date 
Disposition 
Primary Reason for Screen 
Failure/Discontinuation 
100 
100001 
Test Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
Screening, 
Baseline, Visit 3 
(Day 7), Visit 4 
(Day14), Visit 5 
(Day 21), Visit 6 
(Day 28) ET, EOS, 
US  
DDMMMYYYY 
Screened, Screen 
failure, 
Randomized, FU 
1, FU 2, FU 3, 
Discontinuated, 
Completed 
 
xxxxxxxxxxxxxxxxxxxx 
 


 
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Page 71 of 87 
Listing 16.1.1.2 
Randomized Patients Not Included in the Safety, PP and mITT Populations, Randomized Subjects  
 
Site Patient ID 
Treatment Group 
Not Included Population 
Reason for Exclusion 
100 
100001 
Test Product, 
Reference, 
Placebo 
PP, mITT, Safety 
xxxxxxxxxx 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
Derived from multiple sources 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 


 
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Page 72 of 87 
Listing 16.1.2 
Protocol Deviations, All Subjects  
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
Derived from multiple sources 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
Site 
Patient 
ID 
Treatment 
Group 
Population 
Date 
Classification 
Category 
Verbatim Text 
100 
100001 
Test Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
DDMMMYYYY 
Major, Minor 
Subject Dosing, 
Inclusion/Exclusion 
criteria, ect… 
 


 
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Page 73 of 87 
Listing 16.1.3.1 
Subject Demographics and Characteristics, All Subjects 
Patient 
ID 
Treatment 
Group 
Population 
Date of Informed 
Consent 
Date of Birth  
Age (Years) 
Sex 
Ethnicity 
Race 
100001 
Test Product, 
Reference, 
Placebo 
Safety, 
PP, mITT 
DDMMMYYYY 
DDMMMYYYY 
xxx 
Male, 
Female 
Hispanic 
or Latino, 
Not 
Hispanic 
or Latino 
American Indian or 
Alaska Native, 
Asian, Black or 
African American, 
Native Hawaiian or 
Other Pacific 
Islander, White, 
Other (xxx) 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF page 7 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Page 74 of 87 
Listing 16.1.3.2 
Medical History, All Subjects 
Patient ID 
Treatment 
Group 
Population 
MH 
Seq 
System Organ Class /  
Preferred Term /  
MH / Procedure Term Verbatim 
Start Date 
End date 
Ongoing 
100001 
Test Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
xxx 
xxxxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxxxxx 
DDMMYYYY 
 
DDMMYYYY 
 
Yes/ 
No 
MH: Medical History 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 8, 9 
 Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Page 75 of 87 
Listing 16.1.3.3 
Laboratory Results, All Subjects 
Patient 
ID 
Treatment 
Group 
Population 
Visit 
Lab Seq 
Lab Test 
Sample 
collected 
Result 
Reason fot Test Not 
Done 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
Screening, 
Baseline, 
ET, EOS, 
US 
xxx 
HIV, Hepatitis B, 
Hepatitis C, 
Syphilis, 
Pregnancy 
Yes, No 
Positive, 
Negative 
xxxxxx 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 16, 17, 30, 87, 112, 113 
 Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Page 76 of 87 
Listing 16.1.3.4 
Prior Medications, All Subjects 
Patient 
ID 
Treatment 
Group 
Population 
PM 
Seq 
WHO-DD ATC 
Class Level1/  
WHO-DD ATC 
Class Level 2/  
WHO-DD Preferred 
Term/  
PM Verbatim 
Indication/ Type 
Treatment was 
Given 
Dose/ Unit/ 
Form/ 
Frequency/ 
Route/ 
Start Date/ End 
Date 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
xxx 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxx 
xxxxxx/ 
Medication/Non-drug 
Treatment (xxxxx), 
Surgical/ Diagnostic 
Procedure (xxxxxxx) 
AE, MH, Study 
Indication, 
Prophylactically
, Other 
(xxxxxx) 
xxx.xx/ 
xxxxxx/ 
xxxxxx/ 
xxxxxxxx/ 
xxxxxxxx 
DDMMYYYY/ 
DDMMYYYY, 
Ongoing 
Prior medication: any medications taken within the 30 days prior to the start of the study and with stop dates occurring before the date of first 
administration of the study drug. 
PM: Prior Medication 
AE: Adverse Event 
MH: Medical History 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 97, 98, 99, 101 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 


 
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Page 77 of 87 
Listing 16.2 
Number of Warts and Area, Safety Population 
Patient 
ID 
Treatment 
Group 
Population 
Visit  
Date 
Number of 
Genital 
Warts 
Number of 
Perianal 
Warts 
Area of 
Warts 
(cm2) 
Reason for 
Assessment Not 
Done 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, 
PP, mITT 
Screening, Baseline, 
Visit 3 (Day 7), 
Visit 4 (Day 14), 
Visit 5 (Day 21), 
Visit 6 (Day 28), 
ET, EOS, US 
DDMMYYYY 
xxx 
xxx 
xxx 
xxxxxxxxxxxx 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 18, 31, 48, 60, 72, 86, 128 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Page 78 of 87 
Listing 16.3.1 
Vital Signs, Safety Population 
[1] 1 = Temperature (°C). 2 = Pulse rate (beats per minute). 3 = Systolic Blood Pressure (mmHg). 4 = Diastolic Blood Pressure (mmHg).  
ND: Not Done 
CS: Clinically Significant 
NCS: Not Clinically Significant 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
 
Patient 
ID 
Treatment 
Group 
Population Visit 
Date 
Test 
[1] 
Result/ 
Not 
Done 
5 min 
Rest 
Clinical 
Significance 
Reason 
for Test 
Not 
Done 
Reason for 
Not Rest 5 
min 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, 
PP, mITT 
Screening, 
Baseline, Visit 3 
(Day 7), Visit 4 
(Day 14), Visit 5 
(Day 21), Visit 6 
(Day 28), EOS, 
ET, US 
DDMMMYYYY 
1, 2, 
3, 4 
xx.xx, 
xxx, 
ND 
Yes, 
No 
CS, NCS 
xxxxx 
xxxxx 
Source: <Dataset> 
CRF pages 10, 11, 24, 25, 46, 47, 58, 59, 70, 
71, 80, 81, 118, 119 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
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Page 79 of 87 
Listing 16.3.2 
Physical Examinations, All Subjects 
Patient 
ID 
Treatment 
Group 
Population 
Visit 
Height 
(cm) 
Weight 
(kg) 
Body System 
Result 
Clinical 
significance 
Finding (if 
Abnormal)/ 
Reason (if not 
done) 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
Screening, 
Baseline, 
EOS, ET, 
US 
xxx.xx 
xxx.xx 
General Appearance, 
Heart/Cardivascular, 
Lungs, 
Gastrointestina, 
Ear/Nose:/Throat, 
Extremities, Skin, 
[Other]  
Normal, 
Abbnormal, 
Not Done 
CS, NCS 
xxxxxx 
CS: Clinically Significant 
NCS: Not Clinically Significant 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 12-15, 26-29, 82-85, 114-117 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Page 80 of 87 
Listing 16.3.3 
Study Drug Dispensation and Return, Safety Population  
Patient 
ID 
Treatment 
Group 
Population 
Visit 
Dispensation 
Date/ Time 
Drug Dispensed 
Weight (gram) 
Return Date 
Drug Returned 
Weight (gram) 
Reason for 
no Return 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
Baseline, 
Visit 3 (day 
7), Visit 4 
(Day 14), 
Visit 5 (day 
21), Visit 6 
(Day 28), 
EOS, ET, 
US 
DDMMMYYYY/ 
HH24:MI 
x.xx 
DDMMMYYYY 
x.xx 
xxxxx 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 41, 52, 53, 61, 62, 73, 74, 88, 120, 
121, 126 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
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Page 81 of 87 
Listing 16.3.4 
Study Drug Administrations, Safety Population 
Patient ID 
Treatment Group 
Population 
Day 
Date of Application  
Time of AM 
Application 
Time of PM 
Application 
100001 
Test Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
Day 1, Day 2, Day 3, 
Day 8, Day 9, Day 
10, Day 15, Day 16, 
Day 17, Day 22, Day 
23, Day 24 
DDMMMYYYY 
HH24:MI 
HH24:MI 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
 
Source: <Dataset> 
CRF page 102 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
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Page 82 of 87 
Listing 16.3.5 
Diary Card Dispensation and Return, and Treatment Compliance, Safety Population 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
 
Patient 
ID 
Treatment 
Group 
Population 
Visit 
Diary Card 
Dispensed 
Diary Card 
Return 
Reason for Diary 
Card not 
Dispensed/Returned 
Treatment 
Compliance (%) 
100001 
Test Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
Visit 3 (Day 7), 
Visit 4 (Day 14), 
Visit 5 (Day 21),  
Visit 6 (Day 28), 
 EOS, ET, US 
Yes, No 
Yes, No 
xxxxxxx 
xxx 
Source: <Dataset> 
CRF pages 42, 45, 54, 57, 66, 69, 78, 92, 125, 129 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
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Page 83 of 87 
Listing 16.3.6 
Concomitant Medications, Safety Population 
Patient 
ID 
Treatment 
Group 
Population 
CM 
Seq 
WHO-DD ATC 
Class Level1/  
WHO-DD ATC 
Class Level 2/  
WHO-DD Preferred 
Term/  
CM Verbatim 
Indication/ Type 
Treatment was 
Given 
Dose/ Unit/ 
Form/ 
Frequency/ 
Route/ 
Start Date/ End 
Date 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, 
PP, mITT 
xxx 
xxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxxx 
xxxxxx/ 
Medication/Non-drug 
Treatment (xxxxx), 
Surgical/ Diagnostic 
Procedure (xxxxxxx) 
AE, MH, Study 
Indication, 
Prophilactically, 
Other (xxxxxx) 
xxx.xx/ 
xxxxxx/ 
xxxxxx/ 
xxxxxxxx/ 
xxxxxxxx 
DDMMYYYY/ 
DDMMYYYY, 
Ongoing 
Concomittant medication: any medications taken within 30 days prior to the start of the Study Treatment and through the final study visit. 
CM: Concomittent Medication 
AE: Adverse Event 
MH: Medical History 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 97, 98, 99, 101 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 


 
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Page 84 of 87 
Listing 16.3.7  
Site Reaction, Safety Population 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 32-34, 49-51, 63-65, 75-77, 89-
91, 122-124 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 
Patient 
ID 
Treatment 
Group 
Population 
Visit  
Assessment 
Assessement 
Date  
Site Reaction 
Severity 
Reason for no 
Assement 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
Baseline/ Visit 
3 (Day 7), 
Visit 4 (Day 
14), Visit 5 
(Day 21), ET, 
EOS, US 
Yes, No 
DDMMYYYY 
Erythema, 
Dryness, 
Burning/Stinging, 
Erosion, Edema, 
Pain, Itching, 
Bleeding 
Absent, 
Mild, 
Moderate, 
Severe 
xxxxxxx 


 
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Page 85 of 87 
Listing 16.3.8.1 
Adverse Events by System Organ Class, Preferred Term, Frequency and Severity, Safety Population 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
Source: <Dataset> 
CRF pages 93, 94 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 
 
 
 
 
Patient ID 
Treatment 
Group 
Population 
AE 
Seq 
System Organ Class/  
Preferred Term/  
AE Verbatim 
Start Date/Time 
Stop Date/Time 
Frequency 
Severity 
100001 
Test Product, 
Reference, 
Placebo 
Safety, PP, 
mITT 
xx 
xxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxxxx 
DDMMYYYY/ 
HH24:MI 
DDMMYYYY/ 
HH24:MI, 
Ongoing 
Single 
occurrence, 
Intermittent, 
Continuous 
Mild, 
Moderate, 
Severe 


 
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Listing 16.3.8.2 
Adverse Events by System Organ Class, Preferred Term, Seriousness, Treatment Unblinding and Discontinuation of the Subject from 
the Study, Safety Population 
[1] 1 = Death. 2 = Life-Threatening. 3 = Hospitalization. 4 = Prolongation of Hospitalization. 5 = Congenital anomaly / Birth defec. 6 = Persistent 
or significant disability / Incapacity. 7 = Other Important Medical Event 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
Patient 
ID 
Treatment 
Group 
Population 
AE 
Seq 
System Organ 
Class/  
Preferred Term/  
AE Verbatim 
Seriousness 
SAE 
Criteria [1] 
Treatment 
Unblinding/ Date 
and Time 
AE causes Subject 
Discontinuation from 
the Study 
100001 
Test Product, 
Reference, 
Placebo 
Safety, 
PP, mITT 
xx 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx 
Yes, No 
1, 2, 3, 4, 
5, 6, 7 
Yes, No/ 
DDMMYYYY/ 
HH24:MI 
Yes, No 
Source: <Dataset> 
CRF pages 94, 95, 96 
Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials> 


 
Protocol: 16-POD-001  
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Page 87 of 87 
Listing 16.3.8.3 
Adverse Events by System Organ Class, Preferred Term, Causality, Action Taken with the Study Drug, Outcome, Safety Population 
[1] 1 = Related. 2 = Probably Related. 3 = Possibly Related. 4 = Probably Not Related, 5 = Not Related. 6 = Aleternative Ethiology. 
[2] 1 = None. 2 = Drug interrupted. 3 = Drug Withdrawn. 4 = Not Applicable. 
[3] 1 = None. 2 = Medication Administered. 3 = Non-Drug Treatment. 4 = Other. 
[4] 1 = Reolved. 2 = Resolved with Sequelae. 3 = Improving. 4 = Still present and unchanging. 5 = Death. 
Test Product: Podofilox Topical Gel 0.5% 
Reference: Condylox® Gel 0.5% 
Placebo: vehicle that matches the test product 
 
 
 
Patient 
ID 
Treatment 
Group 
Population 
AE 
Seq 
System Organ 
Class /  
Preferred Term /  
AE Verbatim 
Causality [1] 
Action Taken 
with the study 
Drug [2] 
Other Action 
Taken [3] 
Outcome [4] 
Death Date 
100001 
Test 
Product, 
Reference, 
Placebo 
Safety, 
PP, mITT 
xx 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
1, 2, 3, 4, 5, 
6 
1, 2, 3, 4 
1, 2, 3, 4 
1, 2, 3, 4, 5 
DDMMYYYY 
Source: <Dataset> 
CRF pages 93, 95, 96 
           Snapshot Data DD-MMM-YYYY 
Program Name: <Pgm name>   
Date: YYYY-MM-DD Time: HH:MM:SS 
Programmer: <Programmer Initials>