Comparison Between Podofilox Topical Gel 0.5% and Allergan's Condylox® Gel 0.5% for External Anogenital Warts

Study Overview
=================
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study design and recommendations according to Office of Generic Drugs (OGD) of U.S. Food and Drug Administration (FDA) Draft Guidance for Podofilox recommendations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.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo- Controlled, Study of Hyloris Developments' Podofilox Topical Gel 0.5% Compared to Allergan's Condylox® Gel 0.5% in Male and Female Patients With External Anogenital Warts.

Conditions
-----------------
External Anogenital Warts

Intervention / Treatment
-----------------
* Drug: Podofilox Gel 0.5%
* Drug: Condylox Topical Gel 0.5%
* Drug: Placebo Gel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide written informed consent prior to participating in this study. 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. Females of childbearing potential may be enrolled if they practice a method of birth control with a reliability of at least 90%. 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. Any female subject with childbearing potential has a negative urine pregnancy test at Baseline. Negative HIV test within 4 weeks before Baseline. Exclusion Criteria: Female subjects who are pregnant or lactating or planning to become pregnant during the study period. Hypersensitivity or intolerance to Podofilox or any component of the formulation. History of previous unsuccessful treatment with any formulation of Podofilox. Wart area that is greater than 10 cm2. 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). Primary or secondary immunodeficiency. Known presence of diabetes type I or II. Local irritation in any treatment area that would interfere with treatment. Use within 4 weeks prior to baseline of any: 1) treatment for anogenital warts, 2) systemic corticosteroids, or 3) systemic immunosuppressive drug. 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. Patients known to abuse alcohol and/or drugs, or with a history of chronic alcohol or drug abuse that may result in protocol noncompliance. 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. Subjects who in the opinion of the investigator, are unlikely to be able to follow the restrictions of the protocol and complete the study Employee (or employee's family member) of the research center or private practice, CRO or Sponsor, or subjects who have a conflict of interest. Subjects living (e.g., siblings, spouses, relatives, roommates) in the same household cannot be enrolled in the study at the same time. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Podofilox Gel 0.5 %<br>Podofilox Gel 0.5% twice a day, three days following by four days of discontinuation, up to four cycles | Drug: Podofilox Gel 0.5%<br>* Apply twice daily for three consecutive days, then discontinuing for four consecutive days, up to four treatment cycles<br>|
| Active Comparator: Condylox Topical Gel 0.5%<br>Condylox Topical Gel 0.5% twice daily, three days following by four days of discontinuation, up to four cycles | Drug: Condylox Topical Gel 0.5%<br>* Apply twice daily for three consecutive days, then discontinuing for four consecutive days, up to four treatment cycles<br>|
| Placebo Comparator: Placebo Gel<br>Subjects in this arm will receive a vehicle that matches the test product, except for the inclusion of the active ingredient | Drug: Placebo Gel<br>* Apply twice daily for three consecutive days, then discontinuing for four consecutive days, up to four treatment cycles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Subjects With Total Disappearance of All Warts Within All Treated Areas. | The primary endpoint is the Number and Percentage of subjects in the per protocol (PP) population with treatment success defined as total disappearance of all warts within all treated areas. | 28 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Application Site Reaction Scores (Erythema, Dryness, Burning/Stinging, Erosion, Edema, Pain, Itching, and Bleeding) Per Skin Reaction Scale. | 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. 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. Skin Reaction Scale will be used absent, mild (slight, barely perceptible), moderate (distinct presence) and severe (marked, intense). | 28 days (at visit 6) | 
| Analysis of Safety Variables Will be Based on All Adverse Events (AE). | AEs will be summarized based on the frequency of AEs and their severity for all treated subjects. | 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, a total of up to 65 days. |