A Bioequivalence Study With Clinical Endpoints Comparing Adapalene and Benzoyl Peroxide Topical Gel 0.1%/2.5% (Actavis Mid-Atlantic LLC) To Epiduo™ (Adapalene and Benzoyl Peroxide) Gel 0.1%/2.5% (Galderma Laboratories, L.P.) in the Treatment of Mild to Severe Acne Vulgaris

Acne Vulgaris Clinical Trial

Official title:

A Multicenter, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing Adapalene and Benzoyl Peroxide Topical Gel 0.1%/2.5% (Actavis Mid-Atlantic LLC) To Epiduo™ (Adapalene and Benzoyl Peroxide) Gel 0.1%/2.5% (Galderma Laboratories, L.P.) and Both Active Treatments to Topical Gel Placebo (Actavis Mid-Atlantic Llc) in the Treatment of Mild to Severe Acne Vulgaris

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01501799
• Other study ID #: ACTA/ADAP/BP/2010
• Status: Completed
• Phase: N/A
• First received: December 27, 2011
• Last updated: December 28, 2011
• Start date: July 2011
• Est. completion date: December 2011

Study information

• Verified date: December 2011
• Source: Actavis Mid-Atlantic LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardIndia: Drugs Controller General of IndiaBelize: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

EPIDUO™ (adapalene and benzoyl peroxide) Gel 0.1%/2.5%, marketed by GALDERMA LABORATORIES, L.P., is a safe and effective topical therapy used for the treatment of acne vulgaris. Actavis Mid-Atlantic LLC has developed a generic formulation of adapalene and benzoyl peroxide topical gel 0.1%/2.5%,and the current study is designed to evaluate the safety and efficacy of this formulation to determine if it is bioequivalent to EPIDUO™.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 885
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Male or nonpregnant female patients must be between the ages of 12 and 40 years old inclusive.

2. Patients who are 18 years of age or older must have provided IEC/IRB approved written informed consent. Patients between the ages of 12 to 17 years of age must have provided IEC/IRB approved written assent; this written assent must be accompanied by an IEC/IRB approved written informed consent from the patient's legally acceptable representative (i.e., parent or guardian). In addition, all patients or their legally acceptable representatives (i.e., parent or guardian) must sign a HIPAA authorization, if applicable.

3. Patients must have a definite clinical diagnosis of mild to severe acne vulgaris (Grade 2, Grade 3 or Grade 4 on the IGE).

4. Patients must have a minimum of 20 inflammatory lesions and a maximum of 100 and a minimum of 25 and a maximum of 100 non-inflammatory lesions (i.e., open and closed comedones) and no more than 2 nodulocystic lesions (i.e., nodules and cysts) at baseline. For the purposes of study treatment and evaluation, these lesions should be limited to the facial treatment area. Lesions involving the eyes, angles of the nose (i.e., the lines around your nostrils and under the nostrils) and scalp should be excluded from the count. Patients may have acne lesions on other areas of the body (e.g., on the back).

5. Female patients of childbearing potential must have been using 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 patients 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 patients must have a negative urine pregnancy test at baseline. A negative result of a pregnancy test having a minimum sensitivity of at least 50 mIU/ml for hCG should be obtained.

6. All male patients 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. 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.

7. Patients must be willing and able to understand and comply with the requirements of the protocol, including attendance at the required study visits.

8. Patients 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. Patients 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).

9. Patients must be in good health and free from any clinically significant disease.

10. Patients 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:

1. Female patients who are pregnant, nursing or planning to become pregnant during study participation (Visit 1 through Visit 5) will be excluded from study participation.

2. Patients who have a known hypersensitivity to benzoyl peroxide, adapalene, and other retinoids, or their excipients will be excluded from study participation.

3. Patients who have conditions that may interfere with the evaluation of acne vulgaris. Such conditions include, but are not limited to the following lesions on the face: rosacea; seborrheic dermatitis; perioral dermatitis; corticosteroid-induced acne or folliculitis; carcinoid syndrome; squamous cell carcinoma; mastocytosis; acneiform eruptions caused by make-up or medication; bacterial folliculitis; facial psoriasis; and facial eczema.

4. Patients who have acne congoblata, acne fulminans, and secondary acne (e.g., chloracne and drug induced acne) will be excluded from participation.

5. Patients who have been treated with systemic antibiotics or systemic anti-acne drugs or systemic anti-inflammatory drugs within 30 days prior to baseline will be excluded from study participation.

6. Patients who have been treated with prescription and/or over-the-counter topical medications for the treatment of acne vulgaris including antibiotics, topical corticosteroids, a-hydroxy/glycolic acid, benzoyl peroxide, or topical anti-inflammatory medications on the face within 14 days prior to baseline will be excluded from study participation.

7. Patients who are currently taking or have been treated with systemic corticosteroids (including intranasal and inhaled corticosteroids) within 30 days prior to baseline will be excluded from study participation.

8. Patients who have started hormonal therapy or changed the dosage of their hormonal therapy within 3 months prior to baseline will be excluded from study participation. The dosage and frequency of use of any hormonal therapy started greater than 3 months prior to baseline must remain unchanged throughout the study (Visit 1 through Visit 5). Hormonal treatments include, but are not limited to, estrogenic and progestational agents such as birth control pills.

9. Patients who use androgen receptor blockers (such as spironolactone or flutamide) will be excluded from study participation.

10. Patients who have received oral retinoids (e.g., isotretinoin) within 180 days prior to study entry,or have used therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed) within 180 days prior to study entry, or have applied topical retinoids (e.g., tretinoin, tazarotene, adapalene) to the face within the 2 weeks prior to baseline will be excluded from study participation.

11. Patients who have received radiation therapy and/or anti-neoplastic agents within 90 days prior to baseline will be excluded from study participation.

12. Patients who have unstable medical disorders that are clinically significant or life-threatening diseases will be excluded from study participation.

13. Patients who have on-going malignancies requiring systemic treatment will be excluded from study participation. In addition, patients who have any malignancy of the skin of the facial area will be excluded from study participation.

14. Patients who have facial hair will be excluded from study participation. Unacceptable facial hair includes, but is not limited to, beards, and long side-burns. A well-trimmed mustache is acceptable. Patients who have performed wax epilation of the face within 14 days prior to baseline will also be excluded from study participation.

15. Patients 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.

16. Patients 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 history will be excluded from study participation.

17. Patients who have participated in an investigational drug study (i.e., patients have been treated with an investigational drug) within 30 days prior to baseline will be excluded from study participation. Patients who are participating in non-treatment studies such as observational studies or registry studies can be considered for inclusion.

18. Patients who have been previously enrolled in this study will be excluded from study participation.

19. Patients who have had within 30 days prior to baseline or during the study cryodestruction or chemodestruction, dermabrasion, photodynamic therapy, acne surgery, intralesional steroids, or x-ray therapy will be excluded from study participation.

20. Patients who have had laser therapy, and electrodessication to the facial area within 180 days prior to study entry will be excluded from participation.

21. Patients who have had cosmetic procedures (e.g., facials) which may affect the efficacy and safety profile of the investigational product within 14 days prior to study entry will be excluded from participation.

22. Patients who have had general anesthesia for any reason and patients who have received neuromuscular blocking agents within 14 days prior to study entry will be excluded from study participation.

23. Patients who have a baseline local irritation score of 3 (severe, marked/intense) as scored using the Application Site Reaction Scale (Section 5.2) will be excluded from participation.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acne Vulgaris

Intervention

Drug:
• adapalene 0.1% and benzoyl peroxide 2.5% topical gel
Dosage form: topical gel Dosage: A pea-sized amount was applied to each affected area of the face Frequency: once daily in the evening Duration: 12 weeks
• EPIDUO
EPIDUO (adapalene 0.1% and benzoyl peroxide 2.5%) Gel
• Placebo (Vehicle Gel)
Vehicle Gel

Locations

Country	Name	City	State
Belize	FXM Research International - Belize	Belize City
India	Bhatia Skin, Laser & Cosmetic Center	Anand Bazar	Indore
India	Swarnakar Super Specialty Centre	Anand Bazar	Indore
India	MS Clinical Research Pvt. Ltd.	Bangalore
India	Raga's Skin Care	Bangalore
India	Skin & Cosmetology Clinic	Banjara Hills	Hyderabad
India	Chamarajpet Skin and Laser Centre	Chamarajpet	Bangalore
India	Sri Gayathri Skin Care & Hair Transplant Centre	Dwarakanagar	Visakhapatnam
India	Rajbal Polyclinic & Research Center	Kalyan Nagar	Bangalore
India	Skin Clinic	RNT Marg	Indore
India	Department of Skin & STD, Kempegowda Institute of Medical Sciences,	V.V. Puram	Bangalore
India	Bhagwan Mahaveer Jain Hospital	Vasanthnagar	Bangalore
India	Department of Dermatology, Durga Bai Deshmukh Hospital	Vidya Nagar	Hyderabad
India	Agrawal Skin & Laser Centre	Vijaya Nagar	Indore
India	B.V. Department of Dermatology King George Hospital	Visakhapatnam
India	Dayal Clinic	Visakhapatnam
India	Skin & Cosmetology	Visakhapatnam
United States	Center for Dermatology Clinical Research Inc.	Fremont	California
United States	Dermatology Consulting Services	High Point	North Carolina
United States	FXM Research Corp.	Miami	Florida
United States	FXM Research Miramar	Miramar	Florida
United States	Adult & Pediatric Dermatology	Overland Park	Kansas
United States	The Indiana Clinical Trials Center	Plainfield	Indiana
United States	Skin Search of Rochester Inc.	Rochester	New York
United States	Haber Dermatology and Cosmetic Surgery Inc.	South Euclid	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Actavis Mid-Atlantic LLC

Countries where clinical trial is conducted

United States,  Belize,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in inflammatory and non-inflammatory lesions from Baseline to Week 12	The mean percent change from Baseline to Visit 5 (End of Treatment) in the inflammatory and non-inflammatory lesion counts.	Week 12	No
Primary	Treatment-emergent adverse events	All adverse events (AEs) and treatment-emergent AEs reported during the study were summarized for the safety assessment. A treatment-emergent AE was defined as any event not present prior to the initiation of treatment with the investigational products or any event present at Baseline that worsened in either intensity or frequency following exposure to investigational products.	12 Weeks	Yes
Primary	Signs and Symptoms of Local Irritation	Patients will be evaluated for any signs and/or symptoms as separate scores of local irritation, including: erythema, dryness, burning / stinging, erosion, edema, pain, scaling, and itching using the following scale: 0 = None; = Mild, barely perceptible; = Moderate, distinctive presence; = Severe, marked/intense	12 Weeks	Yes
Secondary	The proportion of "success" patients at Visit 5 using the IGE	The proportion of "success" patients at Visit 5 using the IGE, where "success" was defined as a two-grade improvement.	12 Weeks	No
Secondary	Mean Percent Change in Total Lesion Count from Baseline to Visit 5	The mean percent change in the total lesion count from Baseline to Visit 5.	12 Weeks	No