This proposed study is a Multicenter, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Bioequivalence Study with Clinical Endpoint to evaluate the Bioequivalence of Clindamycin 1% and Benzoyl Peroxide 5% Gel of Watson Pharma Pvt Ltd and the Reference Listed Benzaclin^® (Clindamycin 1% and Benzoyl Peroxide 5%) Gel of Dermik Laboratories, Business of Sanofi Aventis US LLC, in treatment of subjects with Acne Vulgaris.

Approximately 690 subjects will be enrolled and randomized at multiple study sites to obtain 516 evaluable subjects (172 in each active treatment group and placebo control group) in PP population. An attempt will be made to have the number of subjects equally distributed amongst sites

Subject participation will last for 70 days (70 days of double-blind study treatment).

The study objectives of this study are:  

Ø  To evaluate the Bioequivalence and the safety of Clindamycin 1% and Benzoyl Peroxide 5% gel of Watson Pharma Pvt Ltd and the Reference Listed Benzaclin® (Clindamycin 1% and Benzoyl Peroxide 5%) gel of Dermik Laboratories, Business of Sanofi Aventis US LLC in the treatment of subjects with Acne Vulgaris.

Ø  To demonstrate the superiority of the efficacy of the test and reference products over the placebo control in the treatment of acne vulgaris.

STUDY DESIGN AND METHODOLOGY:

This is a randomized, double blind, three-arm, parallel group, placebo control bioequivalence study with clinical endpoint, at multiple study sites, designed to establish bioequivalence of Clindamycin 1% and Benzoyl Peroxide 5% gel of Watson Pharma Pvt Ltd and the Reference Listed Benzaclin^® (Clindamycin 1% and Benzoyl Peroxide 5%) gel of Dermik Laboratories, Business of Sanofi Aventis US LLC in the treatment of subjects with Acne Vulgaris.

Clinical Evaluations will be performed at:

            Visit 1: Baseline Visit (Day 1)

            Visit 2: First Interim Visit (Day 28 ± 4 Days)

            Visit 3: Second Interim Visit (Day 56 ± 4 Days)

            Visit 4: End of Treatment Visit (Day 70 ± 4 Days)

An Unscheduled Visit is allowed at any time, for any reason, if in the Investigator’s opinion it is warranted. If a subject is discontinued from the study during an Unscheduled Visit, the Unscheduled Visit will be referred to as an Early Discontinuation Visit and all procedures scheduled for Visit 4 will be performed. If the Unscheduled Visit is not an Early Discontinuation Visit (i.e., the subject will continue to take part in the study), then all procedures scheduled for Visit 4 will be performed, with the exception of the collection of investigational medicinal product and subject diaries from subjects.

Subjects will be admitted into the study after informed consent has been obtained, a medical history and physical examination (with vital signs) have been performed and inclusion/exclusion criteria have been met. Subjects must have a clinical diagnosis of acne vulgaris to qualify for inclusion in this study.

Each subject will be randomly assigned in a double-blind fashion in a 1:1:1 ratio to treatment with the test product, the reference product or the placebo control. The Investigator or designee will dispense blinded investigational product.

At each visit, the following procedures will be performed: a physical examination (with vital signs) will be conducted; counts of the facial comedones (open and closed), papules, pustules and nodulo-cystic lesions will be performed; the Investigator’s Global Assessment (IGA) and UPT for female volunteers (Serum pregnancy test at screening) will be performed; the signs and symptoms of application site reaction will be assessed.

Safety will be assessed by the monitoring of all adverse events and the monitoring of any application site reactions.

CLINICAL ENDPOINTS:

EVALUATION OF EFFICACY:

The two co-primary endpoints of the study are: (1) mean percent change from baseline to week 10 (study Day 70) in the inflammatory (papules and pustules) lesion count, and (2) mean percent change from baseline to week 10 in the non-inflammatory (open and closed comedones) lesion count.

The primary Bioequivalence comparison is that between the test and reference products for the mean percent change from baseline in the inflammatory lesion counts and the non-inflammatory lesion counts, using the PP study population.

The primary superiority evaluations are the comparisons between each active treatment and the placebo control relative to the mean percent change in the inflammatory lesion counts using the mITT study population “with” & “without” Last Observation Carried Forward (LOCF).

The secondary efficacy measures is the proportion of subjects with clinical response of “success” at week 10, measured using the IGA severity scale, where “success” is defined as an IGA score that is at least 2 grades less than the baseline assessment e.g., Grade 4 [Severe] to Grade 2 [Mild]. Failure should be defined as an IGA score that is the same, higher or one grade lower than the baseline assessment.

The secondary Bioequivalence comparison is that between the test and reference products for the proportion of “success” subjects at week 10, using the PP study population.

EVALUATION OF SAFETY:

An adverse event is defined as any untoward medical occurrence (sign, symptom or laboratory finding), regardless of severity and whether or not attributed to the investigational product. All adverse events, whether observed by an Investigator or Study Coordinator or reported by the subject, whether related to study drug or not related to study drug, shall be documented on the CRF and subject records, together with details, i.e. date of onset, the duration and intensity of each episode, the action taken, the relationship to the investigational product and the degree of severity, the seriousness and the outcome.