Bioequivalence of Adapalene Topical Gel in Patients With Acne Vulgaris

A Randomized, Double-Blind, Multiple-Site, Placebo Controlled, Parallel Design, Clinical Study to Evaluate the Bioequivalence of Adapalene Gel 0.1% (PLIVA Research & Development Ltd.) Compared to Differin® (Adapalene 0.1%) Topical Gel (Galderma Laboratories) in Patients With Acne Vulgaris

The objective of this study was to evaluate the efficacy and safety of the test formulation of adapalene gel 0.1% (PLIVA Research & Development Ltd.) as compared to the already marketed formulation, Differin® (adapalene 0.1%) topical gel (Galderma Laboratories) in patients with acne vulgaris.

Study Overview

• Status: Completed
• Conditions: Acne Vulgaris
• Intervention / Treatment: Drug: Adapalene; Drug: Differin®; Drug: Placebo

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria for Comparative Clinical Endpoint Studies.

Statistical Methods: FDA Bioequivalence Statistical Methods for Comparative Clinical Endpoint Studies.

• Study Type: Interventional
• Enrollment (Actual): 601
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belize
  • Belize City, Belize
    • FXM Research International
  • Belize City, Belize
    • Dermatology and Skin Surgery Centre
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Dermatology Research of Arkansas
  • California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
  • Colorado
    • Denver, Colorado, United States, 80209
      • Cherry Creek Research, Inc.
  • Florida
    • Pembroke Pines, Florida, United States, 33024
      • University Clinical Research, Inc.
  • Georgia
    • Newnan, Georgia, United States, 30263
      • MedaPhase, Inc.
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL Clinical Pharmacology Center, Inc.
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Michigan Center for Research Corportation
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Office of Atoya Breona Adams, MD
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Academic Dermatology Associates
  • New York
    • Rochester, New York, United States, 14609
      • Helendale Dermatology & Medical Spa, LLC
    • Rochester, New York, United States, 14623
      • Dermatology Associates of Rochester, PC
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Office of Zoe Diana Draelos, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University Dermatology Consultants, Inc.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Novum Pharmaceutical Research Services
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Knoxville Dermatology, PC
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Center for Dermatology
    • Houston, Texas, United States, 77030
      • Center for Clinical Studies
    • Houston, Texas, United States, 77058
      • Center for Clinical Studies
    • Tyler, Texas, United States, 75701
      • Dermatology Associates of Tyler
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Advanced Healthcare, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant, non-lactating female, 12-40 years of age inclusive.
• Signed informed consent form, which meets all the criteria of the current FDA regulations. For patients under the age of majority in the state they are enrolled, the patient's parent or legal guardian will be required to sign the consent form and the patient will sign an IRB approved "assent to participate" form.
• If female and of child bearing potential, prepare to abstain from sexual intercourse or use reliable method of contraception during the study (i.e. condom, Intrauterine device, hormonal contraceptives). Patients on hormonal contraceptives must have been on the same hormonal contraceptive for 3 months prior to the baseline visit and continue throughout the duration of the study.
• Have moderate to severe facial acne as defines as: at least 20 but no more that 60 facial inflammatory lesions (papules and pustules) and at least 25 but no more than 100 non-inflamed lesions (open and closed comedones) and have a Physician's Global Assessment score of 3, 4, or 5.

Exclusion Criteria:

• Patient has more than 2 facial nodular lesions, any nodules present will be documented but will not be included in the inflammatory lesion count.
• Patient has active cystic acne.
• Patient has acne conglobate.
• Patient with significant facial hair such as beards or tattoos or excessive facial scarring that, in the Investigator's opinion, may interfere with the evaluation of the patient's acne.
• Patients with facial sunburn.
• Any dermatological condition other than acne vulgaris that, in the Investigator's opinion, may interfere with the evaluation of the patient's acne (e.g. rosacea, psoriasis, dermatitis).
• Females who are pregnant, lactating, or likely to become pregnant during the study.
• History of allergy or sensitivity to adapalene or other retinoids, or history of any drug hypersensitivity or intolerance which, in the Investigator's opinion, would compromise the safety of the patient or the study.
• Significant history or current evidence of chronic infectious disease, system disorder, organ disorder, or other medical condition that, in the Investigator's opinion, would place the study participant at undue risk by participation.
• Use of any topical antibiotics, topical steroids, or topical anti-inflammatory products used on the face, any oral antibiotics known to treat acne, any systemic steroids, or any systemic anti-inflammatory agents (other than the use of non-steroidal anti-inflammatory agents) within 28 days of the first dosing day.
• Use of oral isotretinoin (Accutane®) within 6 months. Use of topical tretinoin (Retin-A®), adapalene (Differin®), tazarotene (Tazorac®), or azelaic acid (Azelex®) within 28 days of the first dosing day.
• Receipt of any drug as part of a research study within 30 days prior to dosing.
• Female patients who are using hormonal contraceptives must have been on the same type and strength of hormonal contraceptive for at least 3 months prior to enrollment in the study and throughout the duration of the study.
• Patients should not use any medicated facial products (soaps, lotions, moisturizers, etc.) or other medicated facial cleansing agents for 14 days prior to study enrollment.
• Previous participation in this study.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Test Product; Adapalene Topical Gel, 0.1%	Drug: Adapalene; 0.1% Topical Gel
Active Comparator: Reference Listed Drug; Differin® (adapalene 0.1%) Topical Gel	Drug: Differin®; 0.1% Topical Gel; Other Names: Adapalene
Placebo Comparator: Placebo; Gel base only	Drug: Placebo; Gel Base

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Reduction from Baseline in Non-Nodular Inflamed Lesion Count	Per Protocol Population (PPP) was assessed for the mean percent reduction compared to baseline in non-nodular lesion count (papules and pustules) at Day 84. If a patient was withdrawn from the study prior to Day 84 for lack of efficacy, then their data was carried forward for this analysis.	84 days
Mean Percent Reduction from Baseline in Non-Inflamed Lesion Count	Per Protocol Population (PPP) was assessed for the mean percent reduction in non-inflamed lesion count (open and closed comedones) compared with baseline at Day 84. If a patient was withdrawn from the study prior to Day 84 for lack of efficacy, then their data was carried forward for this analysis.	84 days
Safety Analysis	All 601 patients randomized and dispensed study drug were included in the safety analysis. The frequency, severity, and relationship to the study drug for adverse events in each treatment group were used to compare the safety of the study medications.	84 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Numerical Reduction in Inflamed Lesion Counts	Secondary measure of bioequivalence using the Intent-to-Treat (ITT) population.	84 Days
Mean Numerical Reduction in Non-Inflamed Lesion Counts	Secondary measure of bioequivalence using the Intent-to-Treat (ITT) population.	84 Days
Proportion of Patients Considered a "Clinical Success" or "Clinical Failure"	Secondary measure of bioequivalence using the Intent-to-Treat (ITT) population. "Clinial Success" or "Clinical Failure" is defined by the Physician's Global Assessment.	84 Days

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: August 13, 2010
• First Submitted That Met QC Criteria: August 13, 2010
• First Posted (Estimate): August 17, 2010

Study Record Updates

• Last Update Posted (Estimate): November 24, 2010
• Last Update Submitted That Met QC Criteria: November 22, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Bioequivalence; Acne Vulgaris
• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Acne Vulgaris; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Dermatologic Agents; Adapalene
• Other Study ID Numbers: 70716202