A Efficacy and Safety of Duac™Compared With Clindamycin Phosphate Gel in the Treatment of Mild to Moderate Acne Vulgaris

Study Overview
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Brief Summary
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This is a multicentre, randomized, assessor-blind, comparator-controlled evaluation of the efficacy, safety, and tolerability of Duac™Once Daily Gel and clindamycin phosphate gel in the topical treatment of mild to moderate facial acne vulgaris. A total of 1020 subjects will be enrolled, 510 per study arm. The subjects will be males and females between 12 and 45 years of age, inclusive, at the time of consent, who have mild to moderate facial acne vulgaris. Subjects will use Duac™Once Daily Gel (once daily in the evening) or clindamycin phosphate gel twice daily (once in the morning and once in the evening) for 12 weeks. The subjects will be evaluated for change in lesion counts, investigator's static global assessment (ISGA), subject's global assessment (SGA), local tolerability and AEs/SAEs at Weeks0, 1, 2, 4, 8, and 12 (or at early withdrawal). In addition, quality of life measures will be performed at every study visit.

Official Title
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A Multicentre, Randomized, Assessor-blind, Comparator-Controlled, Parallel-Group Clinical Trial to Establish the Efficacy and Safety of Duac™(1% Clindamycin as Clindamycin Phosphate and 5% Benzoyl Peroxide) Once Daily Gel Compared With Clindamycin Phosphate Gel (1% Clindamycin as Clindamycin Phosphate) Twice Daily in the Treatment of Mild to Moderate Acne Vulgaris.

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Duac™Once Daily Gel
* Drug: 1% clindamycin phosphate gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between 12 and 45 years of age, inclusive age will be calculated by date of birth, from 0 at birth. Subjects who have: i. A minimum of 17 but not more than 60 facial inflammatory lesions (papules plus pustules), and no more than 1 facial nodular lesion, with NO cystic lesions. and ii. A minimum of 20 but not more than 125 facial noninflammatory lesions (open and closed comedones). Subjects who have an ISGA score of 2 or 3 at Baseline. Subjects 18 years of age or older must provide written informed consent (according to any local or national authorization requirements). Subjects under the legal age of consent must provide assent and have written informed consent of both the subject and a parent or the legal guardian (according to any local or national authorization requirements). Subjects who are willing and able to complete the study, to understand and comply with the requirements of the study, abide by the restrictions, apply the medication as instructed, and return for the required study visits. Subjects who are in good health and free from any clinically significant disease, other than acne vulgaris, that might interfere with the study evaluations. Female subjects of childbearing potential must have a negative pregnancy test at baseline. Sexually active females of childbearing potential participating in the study must use a medically acceptable method of contraception for at least 6 consecutive months prior to start of study treatment, and must use a medically acceptable method of contraception while receiving protocol-assigned product. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant; including perimenopausal women who are less than 2 years from their last menses. Medically acceptable contraceptive methods include the following: Hormonal contraception, including oral, injectable, or implantable methods started at least 6 months prior to screening. Reliable barrier methods include condoms and diaphragms. A cervical cap is also a reliable barrier method, provided that the female subject has never given birth naturally. The combined use of a condom and spermicide constitute 2 forms of acceptable nonhormonal contraception, provided that they are both used properly. The use of spermicide alone and the improper use of condoms are inferior methods of contraception. Subjects with surgical sterilization, including tubal ligation or partner's vasectomy, must use a form of nonhormonal contraception. A barrier method or sterilization plus spermatocide are acceptable. Females who are not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study. Subjects who have been treated with estrogens, androgens, or anti-androgenic agents used for prevention of pregnancy (and not for control of acne) for at least 6 consecutive months prior to the first dose of investigational product may enrol as long as they do not expect to change dose, drug, or discontinue use during the study. Exclusion Criteria: Female subjects who are pregnant, trying to become pregnant, or who are lactating. Subjects who have cystic acne lesions, acne conglobata, acne fulminans, or secondary acne (e.g. chloracne or drug-induced acne). Subjects who have any clinically relevant finding at their baseline physical examination or medical history such as severe systemic diseases or diseases of the facial skin other than acne vulgaris. Subjects who have facial hair that may prevent the accurate assessment of acne vulgaris grade or lesion count. Subjects who have a history or presence of regional enteritis or inflammatory bowel disease (e.g. ulcerative colitis, pseudomembranous colitis, chronic diarrhoea, or a history of antibiotic-associated colitis, bloody diarrhoea) or similar symptoms. Subjects who have used a prohibited medication, or undergone a prohibited procedure or treatment within the required washout period. Subjects who have a known hypersensitivity or previous allergic reaction to any of the active components, lincomycin, or excipients of the investigational product. Subjects who are employees of a clinical research organization involved in the study, Stiefel, or GSK or who are an immediate family member (partner, offspring, parents, siblings, or sibling's offspring) of an employee, the investigator, or his/her study staff. Subjects who have a member of the same household in this study at the same time. Subjects who have used traditional remedies known to affect acne vulgaris within the last 4 weeks. Subjects who have had any major illness within 30 days before study enrolment. Subjects who have any other condition that in the judgement of the investigator would put the subject at unacceptable risk for participation in the study. Subjects who have participated in any clinical trials or taken any investigate drugs within 4 weeks before study enrolment.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duac™Once Daily Gel<br>Subjects will use Duac™Once Daily Gel (once daily in the evening)for 12 weeks. The subjects will be evaluated for change in lesion counts, ISGA, SGA , local tolerability, and AEs/SAEs at Weeks0, 1, 2, 4, 8, and 12 (or at early withdrawal). In addition, quality of life measures will be performed at every study visit | Drug: 1% clindamycin phosphate gel<br>* 1% clindamycin as clindamycin phosphate<br>|
| Active Comparator: 1% clindamycin phosphate gel<br>Subjects will use 1% clinidamycin phosphate gel (twice daily in the morning and evening)for 12 weeks. The subjects will be evaluated for change in lesion counts, ISGA, SGA , local tolerability, and AEs/SAEs at Weeks0, 1, 2, 4, 8, and 12 (or at early withdrawal). In addition, quality of life measures will be performed at every study visit | Drug: Duac™Once Daily Gel<br>* 1% clindamycin as clindamycin phosphate and 5% benzoyl peroxide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Total Lesion Count From Baseline to Week 12 | The assessor performed a count of inflammatory lesions (IL) (papules, pustules, nodules, and cysts), non-inflammatory lesions (NIL) (open and closed comedones) and total lesions (the sum of IL and NIL) at each study visit. Lesion counts were confined to the face. Change from Baseline at Week 12 was calculated as the value at Week 12 minus the value at Baseline. Parameters were estimated using analysis of covariance (ANCOVA) with treatment, center, treatment-by-centre interaction and Baseline lesion count in the model. Missing values were imputed using the last observation carried forward (LOCF), i.e., the last available observation was used to estimate subsequent missing data. | Baseline (Week 0) and Week 12 | 
| Number of Participants With an Improvement of 2 Grades in the Investigator Static Global Assessment (ISGA) Score From Baseline to Week 12 | ISGA success is defined as the improvement of 2 grades or more in the participant's acne severity scale at Week 12. Acne severity of the participants' face was assessed by the assessor using the ISGA scale, ranging from 0 to 4: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than one small IL; 2=mild, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: up to many NILs and ILs, but no more than a few NLs. Missing values were imputed using the LOCF, i.e., the last available observation was used to estimate subsequent missing data. | Baseline (Week 0) and Week 12 | 
| Number of Participants With an Improvement of 2 Grades in the Investigator Static Global Assessment (ISGA) Score From Baseline to Week 12 | ISGA success is defined as the improvement of 2 grades or more in the participant's acne severity scale at Week 12. Acne severity of the participants' face was assessed by the assessor using the ISGA scale, ranging from 0 to 4: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than one small IL; 2=mild, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: up to many NILs and ILs, but no more than a few NLs. Missing values were imputed using the LOCF, i.e., the last available observation was used to estimate subsequent missing data . | Baseline (Week 0) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Inflammatory Lesion Counts and Non-inflammatory Lesion Counts From Baseline to Week 12 | The assessor performed a count of ILs (papules, pustules, nodules, and cysts), NILs (open and closed comedones at each study visit. Lesion counts were confined to the face. Change from Baseline at Week 12 was calculated as the value at Week 12 minus the value at Baseline. Analysis of covariance (ANCOVA) model was used with terms for Baseline lesion count, treatment, and center. Missing values were imputed using the LOCF, i.e., the last available observation was used to estimate subsequent missing data. | Baseline (Week 0) and Week 12 | 
| Percent Change in Inflammatory, Non-inflammatory and Total Lesion Counts From Baseline to Week 12 | The assessor performed a count of ILs (papules, pustules, nodules, and cysts), NILs (open and closed comedones) and total lesions (the sum of ILs and NILs)at each study visit. Lesion counts were confined to the face. Change from Baseline at Week 12 was calculated as the value at Week 12 minus the value at Baseline. Analysis of covariance (ANCOVA) model was used with terms for Baseline lesion count, treatment, and center. Missing values were imputed using the LOCF, i.e., the last available observation was used to estimate subsequent missing data. | Baseline (Week 0) and Week 12 | 
| Number of Participants Who Had an ISGA Score of 0 or 1 at Week 12 | The assessor evaluated the acne severity of the participants' face using the ISGA scale, ranging from 0 to 4: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than one small IL; 2=mild, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: up to many NILs and ILs, but no more than a few NLs. Missing values were imputed using the LOCF, i.e., the last available observation was used to estimate subsequent missing data. | Week 12 |