To Compare the Efficacy and Safety of Clindamycin Phosphate 1.2% / Benzoyl Peroxide 5% Gel of CHL Versus DUAC® Gel

Acne Vulgaris Clinical Trial

Official title:

A Randomized, Double-blind, Multicentric, Parallel-group, Active and Placebo Controlled, Three Arm Clinical Study to Compare the Efficacy and Safety of Clindamycin Phosphate 1.2% / Benzoyl Peroxide 5% Gel (of Cadila Healthcare Limited, India) Versus DUAC® Gel (of Stiefel Laboratories, USA) Versus Placebo (Vehicle Gel) in the Ratio of 2:2:1 Respectively, in Patients With Acne Vulgaris

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02005666
• Other study ID #: CRL/CT/09/11-12
• Status: Completed
• Phase: Phase 3
• Start date: November 2013
• Est. completion date: September 28, 2016

Study information

• Verified date: February 2017
• Source: Cadila Healthcare Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an Randomized, Double-blind, Multicentric, Parallel-group, Active and Placebo Controlled, Three Arm Clinical Study.

The main objective is to evaluate bioequivalence of Test formulation (Clindamycin Phosphate 1.2%/Benzoyl peroxide 5% gel) of Cadila Healthcare with Reference formulation (DUAC® Gel of Stiefel Laboratories)in the ratio of 2:2:1 of Test drug, Reference drug and Placebo respectively.

Total study duration will be for a period of 78 days which includes treatment duration of 77 days.

850 subjects will be enrolled (randomized)as per the inclusion and exclusion criteria mentioned in the protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: September 28, 2016
• Est. primary completion date: September 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Healthy male or non pregnant female aged = 12 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 nodulocystic lesions (i.e., nodules and cysts).

3. Investigator's Global Assessment (IGA) of acne severity grade 2, 3 OR 4

4. Willing to refrain from use of all other topical acne medications or antibiotics during the 11 week treatment period.

5. If female of childbearing potential, willing to use an acceptable form of birth control during the study.

6. Have used the same brand of make-up for a minimum period of 2 weeks prior to randomization, for subjects who use make-up, and agree to not change make-up brands or types during the study.

7. Willing to provide written informed consent or assent (HIPAA consent/authorization, as applicable)

Exclusion Criteria:

1. 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).

2. Patients who have acne conglobata, acne fulminans and secondary acne (e.g.: chloracne and drug induced acne).

3. Excessive facial hair (e.g. beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of acne vulgaris. Well trimmed moustaches are allowed.

4. History of hypersensitivity or allergy to benzoyl peroxide or clindamycin and/or any of the study medication ingredients.

5. Patients who have a severe or intense irritation on the Face.

6. Use within 6 months prior to baseline (Randomization) of oral retinoids (e.g. Accutane®) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).

7. Use for less than 3 months prior to baseline (Randomization) of estrogens or oral contraceptives; use of such therapy is allowed if it will remain constant throughout the study.

8. Use on the face within 1 month prior to baseline (Randomization) 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.

9. Use within 1 month prior to baseline (Randomization) 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.

10. Use within 2 weeks prior to baseline (Randomization) 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.

11. Patients who have had general anesthesia for any reason and patients who have received neuromuscular blocking agents within 14 days prior to study entry (Randomization).

12. Concomitant use of facial product containing glycolic or other acids, masks, washes or soaps containing benzoyl peroxide or salicylic acid, non mild cleansers or moisturizers containing retinol, salicylic or a- or ß-hydroxy acids.

13. Concomitant use of mega-doses of certain vitamins (such as vitamin D and vitamin B12), haloperidol, halogens such as iodide and bromide, lithium, hydantoin and phenobarbital.

14. Facial procedures (chemical or laser peel, microdermabrasion, etc.) within the past 2 weeks or during the study.

15. Concomitant use of tanning booths or sunbathing.

16. A significant medical history of or are currently immunocompromised

17. Have any systemic or dermatologic disease that may affect the evaluation of study results.

18. Have a history of regional enteritis, ulcerative colitis, pseudomembranous colitis or antibiotic-associated colitis.

19. Subjects with clinically significant unstable medical disorders, life-threatening disease, or current malignancies.

20. Subjects who engage in activities that involve excessive or prolonged exposure to sunlight.

21. Subjects with History of Alcohol abuse or other drugs of abuse within 2 years prior to Randomization.

22. Female subjects who are breast-feeding or planning to become pregnant.

23. Subjects who have been treated with an investigational drug or investigational device within a period of 30 days prior to study enrollment.

Related Conditions & MeSH terms

• Acne Vulgaris

Intervention

Drug:
• Clindamycin Phosphate 1.2% / Benzoyl Peroxide 5% Gel
Drug:-1.2% Clindamycin Phosphate/ 5% Benzoyl Peroxide Gel of Cadila healthcare limited Dosage Form:-Gel Dosage:-Thin Layer/Pea sized Frequency:-Once a day ,every evening Duration:-77 consecutive days
• DUAC® Gel
Drug:-DUAC® Gel Dosage Form:-Gel Dosage:-Thin Layer/Pea sized Frequency:-Once a day ,every evening Duration:-77 consecutive days
• Placebo
Drug:-Placebo, Dosage Form:-Gel Dosage:-Thin Layer/Pea sized Frequency:-Once a day ,every evening Duration:-77 consecutive days

Locations

Country	Name	City	State
India	AMC-MET Medical College, Sheth LG General Hospital,	Ahmedabad	Gujarat
India	Dept of Dermatology, Leprosy and STI, Civil Hospital and BJ Medical College,	Ahmedabad	Gujarat
India	NHL Medical College and VS Hospital	Ahmedabad	Gujarat
India	Sanjeevani Hospital,	Ahmedabad	Gujarat
India	Dept of Dermatology, Bhagawan Mahaveer Jain Hospital Millers Road,Vasanthnagar -	Bangalore	Karnataka
India	Dept of Dermatology, Kempegowda Institute of Medical Sciences	Bangalore	Karnataka
India	Sapthagiri Hospital,	Bangalore	Karnataka
India	Postgraduate Institute of Medical Education & Research (PGIMER)	Chandigarh	Punjab
India	Ganga Ram Hospital,	Delhi
India	Gandhi Hospital,	Hyderabad	Andhra Pradesh
India	Osmania General Hospital	Hyderabad	Andhra Pradesh
India	Institute of Post graduate medical and Research	Kolkata	West Bengal
India	M.V. Hospital and research Center	Lucknow	Uttar Pradesh
India	Dept of Dermatology, BYL Nair Hospital and TN medical college, Dr ALNair Road, Mumbai Central,	Mumbai	Gujarat
India	Dept of Skin & STD, JSS Hospital Ramanuja Road, -	Mysore	Karnataka
India	Government Medical Collge	Nagpur	Maharashtra
India	NKP Salve Institute of Medical Siences and Lata Mangeshkar Hospital,	Nagpur	Maharashtra
India	Dr. D Y Patil Hospital and Research Center	Navi Mumbai	Maharashtra
India	Maulana Azad Medical College	New Delhi	Delhi
India	Jehangir Clinical Development Center	Pune	Maharashtra
India	Medipoint Hosp	Pune	Maharashtra
India	Department of Dermatology, New Civil Hospital and Government Medical College	Surat	Gujarat
India	Baroda Medical College	Vadodara	Gujarat
India	King George Hospital	Visakhapatnam	Andrapradesh
United States	Academic Dermatology Associates	Albuquerque	New Mexico
United States	Visions Clinical Research	Boynton Beach	Florida
United States	Discover Research	Bryan	Texas
United States	Dermatology Research Instititue	Coral Gables	Florida
United States	Universal BioPharma Research	Dinuba	California
United States	Minnesota Clinical Study Center	Fridley	Minnesota
United States	Dermatology Specialists	Louisville	Kentucky
United States	International Dermatology Research, Inc.	Miami	Florida
United States	Skin Specialists, PC	Omaha	Nebraska
United States	The Indiana Clinical Trials Center	Plainfield	Indiana
United States	Research Across America	Santa Ana	California
United States	Yardley Dermatology Associates	Yardley	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Cadila Healthcare Limited

Countries where clinical trial is conducted

United States,  India, 

References & Publications (2)

Eller MG, Smith RB, Phillips JP. Absorption kinetics of topical clindamycin preparations. Biopharm Drug Dispos. 1989 Sep-Oct;10(5):505-12. — View Citation

Zouboulis CC, Fischer TC, Wohlrab J, Barnard J, Alió AB. Study of the efficacy, tolerability, and safety of 2 fixed-dose combination gels in the management of acne vulgaris. Cutis. 2009 Oct;84(4):223-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Percent Change From Baseline to Week 11 (Study Day 77) for Inflammatory (Papules and Pustules) Lesions.	Mean percent change from baseline to week 11 (study Day 77) for inflammatory (papules and pustules) lesions in PP populations. The primary endpoint of the study is mean percent change from baseline to week 11 (study Day 77) in the inflammatory (papules and pustules) lesion count.; Papule was Inflammatory lesion; small (< 5mm in diameter), solid palpable lesion, usually with inflamed elevation of the skin that does not contain pus. Pustule was Inflammatory lesion; small (< 5mm in diameter), inflamed skin swelling that is filled with pus. The test product was judged therapeutically equivalent to the reference product in the reduction of inflammatory lesions if the 90% confidence interval was contained within the interval (0.80, 1.25)	week 11
Secondary	Mean Percent Change From Baseline to Week 11 in the Non-inflammatory Lesion Count	Mean percent change from baseline to week 11 in the non-inflammatory lesion count. The mean percent change from baseline to week 11 in the non-inflammatory (open and closed comedones) lesion count in per protocol population . The analysis was same as the analysis performed for the mean percent reduction from baseline to Day 77 in the number of inflammatory lesion count.; Closed Comedone was Non-inflammatory lesion; whitehead, skin-colored or slightly inflamed "bump" in the skin. Open Comedone was Non-inflammatory lesion; blackhead, surface of the plugged sebaceous follicle has a blackish appearance. The test product was judged therapeutically equivalent to the reference product in the reduction of Non inflammatory lesions if the 90% confidence interval was contained within the interval (0.80, 1.25)	week 11
Secondary	Proportion of Subjects With a Clinical Response of "Success" at Week 11	Success was defined as an Investigator Global Assessment (IGA) score that is at least 2 grades less than the baseline assessment.; Percentage of subjects with at least 2 grades improvement in IGA scoring from baseline to week 11 for test, reference and placebo in Per protocol population.; IGA is evaluated in the range of 0 to 4. Grade 0=Clear skin with no inflammatory or non-inflammatory lesions;Grade 1=Almost clear;rare non-inflammatory lesions with no more than one small inflammatory lesion; Grade 2 = Mild severity; greater than grade 1;some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions);Grade 3 = Moderate severity; greater than Grade 2; up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion;Grade 4= Severe; greater than Grade 3;up to many non-inflammatory lesions and may have some inflammatory lesions,but no more than a few nodular lesions	Week 11

External Links

•   1. Feldman S, Careccia RE, Barham KL, et al. Diagnosis and treatment of acne. Am Fam Physician
•   2. NilFroushzadeh MA, Siadat AH, Baradaran EH, Moradi S. Clindamycin lotion alone versus combination lotion of clindamycin phosphate plus Tretinoin versus combination lotion of clindamycin phosphate plus salicylic acid in the topical treatment of mild to
•   3. Irby CE, Yentzer BA, Feldman SR. A Review of Adapalene in the Treatment of Acne Vulgaris. Journal of Adolescent Health
•   6. Barza M, Goldstein JA, Kane A. Systemic absorption of clindamycin hydrochloride after topical application. Journal of the American Academy of Dermatology
•   Cleocin T® Prescribing Information
•   DUAC® Gel Prescribing Information
•   Guin JD, Lummis WL. Comedonal levels of free clindamycin following topical treatment with a 1% solution of clindamycin phosphate. Journal of the American Academy of Dermatology
•   Nacht S, Yeung D, Beasley JN, Anjo MD, Maibach HI. Benzoyl peroxide: percutaneous penetration and metabolic disposition. Journal of the American Academy of Dermatology
•   Plaisnce KI, Drusano GL, Forrest A, Townsend RJ, Standiford HC. Pharmacokinetic evaluation of two dosage regimens of clindamycin phosphate. Antimicrob Agents Chemother
•   U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Draft Guidance for Industry: Acne Vulgaris: Developing Drugs for Treatment.