A multiple center, parallel group study to evaluate the bioequivalence of test drug Clindamycin 1% and Benzoyl Peroxide 5% Gel of Watson and reference drug Benzaclin® (Clindamycin 1% and Benzoyl Peroxide 5%) Gel of Dermik Labs, in treatment of subjects with Acne Vulgaris

Active, not recruiting

• Conditions: Acne Vulgaris

• Registration Number: CTRI/2014/07/004734
• Lead Sponsor: Watson Pharma Pvt Ltd India

Brief Summary

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.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-09-24
• Last Update Posted: 2015-03-30

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: All
• Target Recruitment: 690

Inclusion Criteria

• Healthy male or non-pregnant female aged ≥ 18 and ≤ 40 years with a clinical diagnosis of acne vulgaris 2.
• On the face, ≥25 non-inflammatory lesions (i.e., open and closed comedones) and ≥ 20 inflammatory lesions (i.e., papules and pustules) and ≤ 2 nodulocysticlesions (i.e., nodules and cysts).
• For the purposes of study treatment and evaluation, these lesions should be limited to the facial treatment area.
• Counts of nodules and cysts should be reported separately and not included in the inflammatory or non-inflammatory lesion counts.
• Lesions involving the eyes and scalp should be excluded from the count.
• Subjects must have Investigator’s Global Assessment (IGA) of acne severity grade 2, 3, or 4.
• Willing to refrain from use of all other topical acne medications or antibiotics during the 10 week treatment period.
• Subjects must have provided IEC/IRB approved written informed consent.
• Subjects may have acne lesions on other areas of the body (e.g., on the back).
• Female subjects of childbearing potential must use accepted methods of birth control or must agree to continue to practice abstinence, from 30 days prior to study entry to 30 days after the last administration of study drug.
• All female subjects are considered to be of childbearing potential unless they have been surgically sterilized or have been postmenopausal for at least 1 year.
• Abstinence is an acceptable method of birth control.
• Any of the following methods of birth control are acceptable: oral contraceptives, contraceptive patches/implants (e.g., Norplant®) Depo-Provera®, double barrier methods (e.g., condom and spermicide) or IUD.
• Female subjects must have a negative serum pregnancy test at baseline.
• All male subjects must agree to use accepted methods of birth control with their partners, from the day of the first dose administration to 30 days after the last administration of study drug.
• Subjects must be willing and able to understand and comply with the requirements of the protocol, including attendance at the required study visits.
• Subjects must be willing to refrain from using any other treatments for acne vulgaris, including antibiotics, other than the investigational product, for acne present on the face.
• Subjects may use other topical acne treatments that do not have significant or measurable systemic absorption for treatment of acne of the back, shoulders and chest (e.g. benzoyl peroxide, salicylic acid).
• Subjects must be in good health and free from any clinically significant disease at the discretion of the Investigator.
• Subjects having normal 12-lead electrocardiogram (ECG) as certified by physician.
• Subjects having normal chest X-Ray (Postero Anterior view) 14.
• Subjects who use make-up must have used the same brands/types of make-up for a minimum period of 14 days prior to study entry and must agree to not change make-up brand/type or frequency of use throughout the study.

Exclusion Criteria

• History of hypersensitivity or allergy to clindamycin or benzoyl peroxide or clindamycin and/or any of the study medication ingredients.
• Presence of any skin condition that would interfere with the diagnosis or assessment of acne vulgaris (e.g., on the face: rosacea, dermatitis, psoriasis, squamous cell carcinoma, eczema, acneform eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis).
• Excessive facial hair (e.g. beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of acne vulgaris 4.
• Use within 6 months prior to baseline of oral retinoids (e.g. Accutane®) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).
• Use for less than 3 months prior to baseline of estrogens or oral contraceptives; use of such therapy must remain constant throughout the study 6.
• Use on the face within 1 month prior to baseline or during the study of: 1) cryodestruction or chemodestruction, 2) dermabrasion, 3) photodynamic therapy, 4) acne surgery, 5) intralesional steroids, or 6) x-ray therapy.
• Use within 1 month prior to baseline of: 1) spironolactone, 2) systemic steroids, 3) systemic antibiotics, 4) systemic treatment for acne vulgaris (other than oral retinoids, which require a 6-month washout), or 5) systemic anti-inflammatory agents.
• Use within 2 weeks prior to baseline of: 1) topical steroids, 2) topical retinoids, 3) topical acne treatments including over-the-counter preparations, 4) topical anti-inflammatory agents, 5) medicated cleansers or 6) topical antibiotics.
• Subjects who have acne congoblata, acne fulminans, and secondary acne (e.g., chloracne and drug induced acne) will be excluded from participation.
• Female subjects who are pregnant, nursing or planning to become pregnant during study participation (Visit 1 through Visit 4 and 30 days post visit 4) will be excluded from study participation.
• Subjects who have received radiation therapy and/or anti-neoplastic agents within90 days prior to baseline will be excluded from study participation.
• Subjects who have on-going malignancies requiring systemic treatment will be excluded from study participation.
• In addition, subjects who have any malignancy of the skin of the facial area will be excluded from study participation.
• Subjects who engage in activities that involve excessive or prolonged exposure to sunlight or weather extremes, such as wind or cold, will be excluded from study participation.
• Subjects who have facial sunburn will be excluded from study participation 16.
• Subjects who consume excessive amounts of alcohol (greater than two drinks per day) or use drugs of abuse (including, but not limited to, cannabinoids and cocaine) as judged by their medical history will be excluded from study participation.
• History or presence of significant smoking (more than 10 cigarettes or bidis/day or consumption of tobacco products).
• Systolic blood pressure less than 90 mm Hg or more than 140 mm Hg, Diastolic blood pressure less than 60 mm Hg or more than 90 mm Hg and Pulse rate less than 50 beats/minute or more than 100 beats/minute 19.
• Subjects who have participated in an investigational drug study (i.e., subjects have been treated with an investigational drug) within 3 months prior to baseline will be excluded from study participation.
• Subjects who are participating in non-treatment studies such as observational studies or registry studies can be considered for inclusion.
• Major illness during 3 months before screening 21.
• Subjects who have been previously enrolled in this study will be excluded from study participation.
• Subjects who have had laser therapy and electrodessication to the facial area within 180 days prior to study entry will be excluded from participation.
• Subjects who have had cosmetic procedures (e.g., facials) which may affect the efficacy and safety profile of the investigational medicinal product within 14 days prior to study entry will be excluded from participation.
• Subjects who have had general anesthesia for any reason and subjects who have received neuromuscular blocking agents within 14 days prior to study entry willbe excluded from study participation.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
EVALUATION OF SAFETY/EFFICACY	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)
1. Mean% change from baseline to week 10 in the inflammatory (papules and pustules) lesion count	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)
2. Mean% change from baseline to week 10 in the non-inflammatory (open and closed comedones) lesion count	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)
3. The primary BE comparison is between the T and R for the mean% change from baseline in the inflammatory & non-inflammatory lesion counts using the PP study population	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)
4. Incidence of all AEs reported during study will be summarized using the MedDRA dictionary	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)

Secondary Outcome Measures

Name	Time	Method
The secondary efficacy evaluation is based on the secondary efficacy measure, i.e. the proportion of “success†subjects at week 10, measured using the IGA severity score (see section 6.2) where “success†is defined as an IGA score that is at least 2 grades less than the baseline assessment and “failure†is defined as an IGA score that is the same, higher or one grade lower than the baseline assessment.	Visit 1: Baseline Visit (Day 1)

Trial Locations

Locations (18)

Apollo Hospital; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

Bhagwan Mahaveer Jain Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Care Hospital; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

Father Muller Medical College Hospital; 🇮🇳 Kannada, KARNATAKA, India

Global Hospital; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

HCG Multi Specialty Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Jehangir Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Kempegowda Institute Of Medical Sciences; 🇮🇳 Bangalore, KARNATAKA, India

King George Hospital; 🇮🇳 Visakhapatnam, ANDHRA PRADESH, India

M. V. Hospital & Research Centre; 🇮🇳 Lucknow, UTTAR PRADESH, India

Scroll for more (8 remaining)

Apollo Hospital

🇮🇳Hyderabad, ANDHRA PRADESH, India

Dr Radha Shah

Principal investigator

4023607777

drradhashah@gmail.com