Acne Vulgaris
Conditions
Keywords
Acne Vulgaris, DUAC, CADILA, CLIANTHA
Brief 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.
Interventions
DRUGClindamycin 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
DRUGDUAC® Gel
Drug:-DUAC® Gel Dosage Form:-Gel Dosage:-Thin Layer/Pea sized Frequency:-Once a day ,every evening Duration:-77 consecutive days
DRUGPlacebo
Drug:-Placebo, Dosage Form:-Gel Dosage:-Thin Layer/Pea sized Frequency:-Once a day ,every evening Duration:-77 consecutive days
Sponsors
Zydus Lifesciences Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 40 Years
Healthy volunteers
No
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 α- or β-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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline to Week 11 (Study Day 77) for Inflammatory (Papules and Pustules) Lesions. | week 11 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline to Week 11 in the Non-inflammatory Lesion Count | week 11 | 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) |
| Proportion of Subjects With a Clinical Response of Success at Week 11 | 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 |
Countries
India, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test-Cadila Healthcare Limited 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 | 338 |
| Reference-DUAC® Gel DUAC® Gel Dosage Form:-Gel Dosage:-Thin Layer/Pea sized Frequency:-Once a day ,every evening Duration:-77 consecutive days | 343 |
| Placebo Placebo, Dosage Form:-Gel Dosage:-Thin Layer/Pea sized Frequency:-Once a day ,every evening Duration:-77 consecutive days | 169 |
| Total | 850 |
Baseline characteristics
| Characteristic | Test-Cadila Healthcare Limited | Reference-DUAC® Gel | Placebo | Total |
|---|---|---|---|---|
| Age, Customized <18 | 86 Participants | 87 Participants | 47 Participants | 220 Participants |
| Age, Customized 18 - 40 | 252 Participants | 256 Participants | 122 Participants | 630 Participants |
| Age, Customized 41 - 65 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >65 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 240 Participants | 245 Participants | 121 Participants | 606 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 8 Participants | 1 Participants | 18 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 44 Participants | 50 Participants | 23 Participants | 117 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other pacific Islander | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Non Hispanic/Latino | 294 Participants | 293 Participants | 146 Participants | 733 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 83 Participants | 88 Participants | 45 Participants | 216 Participants |
| Sex/Gender, Customized Female | 152 Participants | 151 Participants | 66 Participants | 369 Participants |
| Sex/Gender, Customized Male | 186 Participants | 192 Participants | 103 Participants | 481 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 338 | 0 / 343 | 0 / 169 |
| other Total, other adverse events | 59 / 338 | 61 / 343 | 29 / 169 |
| serious Total, serious adverse events | 0 / 338 | 0 / 343 | 0 / 169 |
Outcome results
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)
Time frame: week 11
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test-Cadila Healthcare Limited | Mean Percent Change From Baseline to Week 11 (Study Day 77) for Inflammatory (Papules and Pustules) Lesions. | -67.6 percentage of mean change from baseline | Standard Deviation 28.39 |
| Reference-DUAC® Gel | Mean Percent Change From Baseline to Week 11 (Study Day 77) for Inflammatory (Papules and Pustules) Lesions. | -71.3 percentage of mean change from baseline | Standard Deviation 25.98 |
| Placebo | Mean Percent Change From Baseline to Week 11 (Study Day 77) for Inflammatory (Papules and Pustules) Lesions. | -51.9 percentage of mean change from baseline | Standard Deviation 33.99 |
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)
Time frame: week 11
Population: Total randomized subjects 850,in 2:2:1 ratio(Test:338,Reference:343,Placebo:169).80 subjects withdrawn,770 subjects completed study.Efficacy analysis done in Per Protocol (PP)Population, total 253 subjects were excluded from total randomized subjects.For efficacy analysis,597 subjects considered in PP population (Test:236,Reference:233,Placebo:128)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test-Cadila Healthcare Limited | Mean Percent Change From Baseline to Week 11 in the Non-inflammatory Lesion Count | -61.7 percentage of change | Standard Deviation 29.5 |
| Reference-DUAC® Gel | Mean Percent Change From Baseline to Week 11 in the Non-inflammatory Lesion Count | -61.3 percentage of change | Standard Deviation 28.46 |
| Placebo | Mean Percent Change From Baseline to Week 11 in the Non-inflammatory Lesion Count | -42.0 percentage of change | Standard Deviation 34.99 |
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
Time frame: Week 11
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test-Cadila Healthcare Limited | Proportion of Subjects With a Clinical Response of Success at Week 11 | Failure Rate | 196 Participants |
| Test-Cadila Healthcare Limited | Proportion of Subjects With a Clinical Response of Success at Week 11 | Success Rate | 40 Participants |
| Reference-DUAC® Gel | Proportion of Subjects With a Clinical Response of Success at Week 11 | Failure Rate | 201 Participants |
| Reference-DUAC® Gel | Proportion of Subjects With a Clinical Response of Success at Week 11 | Success Rate | 32 Participants |
| Placebo | Proportion of Subjects With a Clinical Response of Success at Week 11 | Failure Rate | 118 Participants |
| Placebo | Proportion of Subjects With a Clinical Response of Success at Week 11 | Success Rate | 10 Participants |