Study STF115287, a Clinical Confirmation Study of GSK2585823 in the Treatment of Acne Vulgaris in Japanese Subjects

Study Overview
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Brief Summary
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This is a multicenter, randomized, single-blinded (investigator's blinded), active-controlled (clindamycin [CLDM] 1% gel), parallel-group study in Japanese subjects with acne vulgaris to demonstrate the efficacy of GSK2585823 (CLDM 1%-benzoyl peroxide [BPO] 3% gel) when applied once or twice daily for 12 weeks. This study will also evaluate the safety of GSK2585823 when applied topically either once or twice daily for 12 weeks.

Detailed Description
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Main inclusion criteria will be 12 to 45 years of age, who have an Investigator Static Global Assessment (ISGA) score of 2 or greater at baseline visit, and have both 17 to 60 facial inflammatory lesions (papules plus pustules) and 20 to 150 facial non-inflammatory lesions (open and closed comedones), including nasal lesions. The primary objectives are to demonstrate the superiority of GSK2585823 twice daily to CLDM twice daily in total lesion counts, and to demonstrate the non-inferiority of GSK2585823 once daily to CLDM twice daily in total lesion counts. The secondary objectives are to demonstrate the non-inferiority of GSK2585823 once daily to CLDM twice daily in inflammatory lesion counts, and to evaluate the efficacy of GSK2585823 once or twice daily compared with CLDM twice daily at each visit. A total of 800 subjects will be enrolled and randomly assigned to one of the groups.

Official Title
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Study STF115287, a Clinical Confirmation Study of GSK2585823 (Clindamycin 1%-Benzoyl Peroxide 3% Gel) in the Treatment of Acne Vulgaris in Japanese Subjects. - A Multicenter, Randomized, Single-blind, Active-controlled, Parallel-group Study -

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: GSK2585823(CLDM 1%-BPO 3% gel)
* Drug: CLDM 1% gel twice daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 12 to 45 years (inclusive) of age in good general health. Subjects must have both on the face: A) A minimum of 17 but not more than 60 inflammatory lesions (papules/pustules), including nasal lesions. And B) A minimum of 20 but not more than 150 non-inflammatory lesions (open/closed comedones), including nasal lesions. An ISGA score of 2 or greater at baseline. Females of childbearing potential and women who are less than 2 years from their last menses must agree to use the contraception. The ability and willingness to follow all study procedures and attend all scheduled visits. The ability to understand and sign a written informed consent form (Written informed consent must be obtained also from the parent or guardian in case of subject under 20 years of age at the time of given consent). Exclusion Criteria: Have any nodule-cystic lesions at baseline. Are pregnant or breast-feeding. Have a history or presence of regional enteritis, inflammatory bowel disease (e.g., ulcerative colitis, pseudomembranous colitis, chronic diarrhea or antibiotic-associated colitis) or similar symptoms. Used any of the following agents on the face within the previous 2 weeks:Topical antibiotics (or systemic antibiotics);Topical anti-acne medications (e.g., BPO, azelaic acid, resorcinol, salicylates);Abradants, facials, or peels containing glycolic or other acids;Masks, washes or soaps containing BPO, sulfacetamide sodium, or salicylic acid;Non-mild facial cleansers (e.g., facial scrub, cleansers containing agents with anti-inflammatory action); Moisturizers that contain retinol, salicylic acid, or α- or β-hydroxy acids;Astringents and toner (Subjects are allowed to enroll in this study, if the subject has been on treatment for more than 2 consecutive weeks prior to start of investigational product use). Used the following agents on the face or performed the following procedure within the previous 4 weeks:Topical corticosteroids (Use of inhaled, intra-articular, or intra-lesional steroids other than for facial acne is acceptable);Facial procedure (such as chemical or laser peel, microdermabrasion, blue light treatment, etc.). Used systemic retinoids within the previous 6 months or topical retinoids on the face within the previous 6 weeks. Received treatment with estrogens, androgens, or anti-androgenic agents within the previous 12 weeks (Subjects who have been treated with the above agents for more than 12 consecutive weeks prior to start of investigational product are allowed to enrol as long as they do not expect to change dose, drug, or discontinue use during the study). Used any medication that in the opinion of the investigator may affect this clinical study or evaluation of the study. Plan to use medications that are reported to exacerbate acne (e.g., mega-doses of certain vitamins, such as vitamin D [>2000 IU/day] and vitamin B12 [>1 mg/day], corticosteroids*, androgens, haloperidol, halogens [e.g., iodide and bromide], lithium, hydantoin, and phenobarbital). *: except the using of topical corticosteroids (e.g., inhaled, intra-articular, or intra-lesional steroids) other than for facial acne. Have a known hypersensitivity or have had previous allergic reaction to any of the components of the investigational product. Used any investigational therapy within the previous 12 weeks, or plan to participate in another clinical study at the same time. Participated in Japanese clinical studies planned by GlaxoSmithKline K.K. in the development of investigational products for acne vulgaris. Are currently abusing drugs or alcohol. Have a significant medical history of being immunocompromised. People as follows and the family members:Employees of GlaxoSmithKline, contract research organization (CRO) or site management organization (SMO);Investigators. Have other conditions that would put the subject at unacceptable risk for participation in the study.

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: GSK2585823(CLDM 1%-BPO 3% gel) once daily<br>Subjects will apply in a quantity sufficient to cover the entire face (including the forehead, nose, cheeks, and chin). Also, the dose regimen will be once daily in the evening/bedtime. | Drug: GSK2585823(CLDM 1%-BPO 3% gel)<br>* Topical gel in 1 g containing clindamycin 10 mg and benzoyl peroxide 30 mg<br>* Other names: GSK2585823;|
| Experimental: GSK2585823(CLDM 1%-BPO 3% gel) twice daily<br>Subjects will apply in a quantity sufficient to cover the entire face (including the forehead, nose, cheeks, and chin). Also, the dose regimen will be twice daily in the morning and evening/bedtime. | Drug: GSK2585823(CLDM 1%-BPO 3% gel)<br>* Topical gel in 1 g containing clindamycin 10 mg and benzoyl peroxide 30 mg<br>* Other names: GSK2585823;|
| Active Comparator: CLDM 1% gel twice daily<br>Subjects will apply in a quantity sufficient to cover the entire face (including the forehead, nose, cheeks, and chin). Also, the dose regimen will be twice daily in the morning and evening/bedtime. | Drug: CLDM 1% gel twice daily<br>* Topical gel containing clindamycin 10 mg/1 g gel<br>* Other names: CLDM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline to Week 12 in Total Lesion Counts. | The investigator (or subinvestigator) counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedones) on the face at each study visit. An open comedone was an open, widely dilated follicle with black-colored sebum, due to melanin and oxidation, and keratinous material that forms a plug, thereby obstructing the pilosebaceous duct. A closed comedone was a closed follicle filled with impacted sebum covered by keratin that has a whitish color. A papule was a small, raised, red, dome-shaped palpable lesion. A pustule was a raised, dome-shaped palpable lesion containing yellow fluid (pus). A nodule might be a raised or deep-seated, dome-shaped palpable lesion of at least 5 millimeters in diameter. Day 1 was Baseline and change from baseline was calculated by subtracting the Baseline value from post-randomization value at Week 12. | Baseline (Day 1) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline to Weeks 1, 2, 4, and 8 in Total Lesion Counts | The investigator (or subinvestigator) counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedones) on the face at each study visit. An open comedone was an open, widely dilated follicle with black-colored sebum, due to melanin and oxidation, and keratinous material that forms a plug, thereby obstructing the pilosebaceous duct. A closed comedone was a closed follicle filled with impacted sebum covered by keratin that has a whitish color. A papule was a small, raised, red, dome-shaped palpable lesion. A pustule was a raised, dome-shaped palpable lesion containing yellow fluid (pus). A nodule might be a raised or deep-seated, dome-shaped palpable lesion of at least 5 millimeters in diameter. Day 1 was Baseline and change from baseline was calculated by subtracting the Baseline value from value at indicated time points. | Baseline (Day 1) and Weeks 1, 2, 4, and 8 | 
| Absolute Change From Baseline to Weeks 1, 2, 4, 8, and 12 in Inflammatory and Non-inflammatory Lesion Counts | The investigator (or subinvestigator) counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedones) on the face at each study visit. An open comedone was an open, widely dilated follicle with black-colored sebum, due to melanin and oxidation, and keratinous material that forms a plug, thereby obstructing the pilosebaceous duct. A closed comedone was a closed follicle filled with impacted sebum covered by keratin that has a whitish color. A papule was a small, raised, red, dome-shaped palpable lesion. A pustule was a raised, dome-shaped palpable lesion containing yellow fluid (pus). A nodule might be a raised or deep-seated, dome-shaped palpable lesion of at least 5 millimeters in diameter. Day 1 was Baseline and change from baseline was calculated by subtracting the Baseline value from value at indicated time points. | Baseline (Day 1) and Weeks 1, 2, 4, 8, and 12 | 
| Percent Change From Baseline to Weeks 1, 2, 4, 8, and 12 in Total, Inflammatory, and Non- Inflammatory Lesion Counts | The investigator (or subinvestigator) counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedones) on the face at each study visit. An open comedone was an open, widely dilated follicle with black-colored sebum, due to melanin and oxidation, and keratinous material that forms a plug, thereby obstructing the pilosebaceous duct. A closed comedone was a closed follicle filled with impacted sebum covered by keratin that has a whitish color. A papule was a small, raised, red, dome-shaped palpable lesion. A pustule was a raised, dome-shaped palpable lesion containing yellow fluid (pus). A nodule might be a raised or deep-seated, dome-shaped palpable lesion of at least 5 millimeters in diameter. Day 1 was Baseline and change from baseline was calculated by subtracting the Baseline value from value at indicated time points.( Weeks 1, 2, 4, 8 and 12) | Baseline (Day 1) and Weeks 1, 2, 4, 8, and 12 | 
| Percentage of Participants With a Minimum 2-grade Improvement From Baseline to Week 12 in Investigator's Static Global Assessment (ISGA) Score | Proportion of participants with at least a 2-Grade Improvement in ISGA was reported using a 5 point scale which indicates Score 0 (Clear): skin with no inflammatory or non-inflammatory lesions, Score 1 (Almost Clear): rare non-inflammatory lesions with no more than rare papules, Score 2 (Mild): greater than Grade 1, some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions), Score 3 (Moderate): greater than Grade 2, many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion, Score 4 (Severe): greater than Grade 3, many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions and 5(very severe): many non-inflammatory and inflammatory lesions and more than a few nodular lesions. May have cystic lesions. The investigator assessed ISGA score at baseline (Week 0/Day 1) and Weeks 1, 2, 4, 8, and 12. The area evaluated ISGA was limited to the face. | Baseline (Day 1) and Week 12 | 
| Percentage of Participants With an ISGA Score of 0 (Clear) or 1 (Almost Clear) at Weeks 1, 2, 4, 8, and 12 | Proportion of participants with at least a 2-Grade Improvement in ISGA was reported using a 5 point scale which indicates Score 0 (Clear): skin with no inflammatory or non-inflammatory lesions, Score 1 (Almost Clear): rare non-inflammatory lesions with no more than rare papules, Score 2 (Mild): greater than Grade 1, some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions), Score 3 (Moderate): greater than Grade 2, many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion, Score 4 (Severe): greater than Grade 3, many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions and 5 (very severe): many non-inflammatory and inflammatory lesions and more than a few nodular lesions. May have cystic lesions. The investigator assessed ISGA score at baseline (Week 0/Day 1) and Weeks 1, 2, 4, 8, and 12. The area evaluated ISGA was limited to the face. | Week 1, 2, 4, 8, and 12 | 
| Percentage of Participants Who Have a Reduction of at Least 50 Percent in Total Lesions | The percentage of participants who had reduction in total lesions (inflammatory and non-inflammatory) of at least 50 percent from Baseline at Weeks 1, 2, 4, 8, and 12 was measured. | Baseline (Day 1) and Week 1, 2, 4, 8, and 12 | 
| Minimum Inhibitory Concentration (MIC) of Clinical Isolates to Antibiotics CLDM and Nadifloxacin (NDFX) | MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism). MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism) for the susceptibility of clinical isolates (Propionibacterium acnes before and after application of the CLDM and NDFX was reported. MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis. | Baseline (Day 1) and Week12 | 
| Change in Investigator Assessment of Tolerability (Erythema, Dryness and Peeling) From Baseline to Weeks 1, 2, 4 and 8 and 12 | Erythema (redness), dryness, and peeling, were evaluated independently by the investigator on a five point scale from 0 to 4 defined as 0-none, 1-very minimal, 2-mild, 3-moderate, 4-severe. Day 1 was Baseline and Change from Baseline was calculated by subtracting Baseline value from value at specified time points (Week 1, 2, 4, 8, and 12). | Baseline (Day 1) and Week 1, 2, 4, 8, and 12 | 
| Change in Participant Assessment of Tolerability ( Itching and Burning/Stinging ) From Baseline to Weeks 1, 2, 4, 8 and 12 | Burning/stinging, itching were evaluated independently by the participant on a five point scale from 0 to 4 defined as 0-none, 1-very minimal, 2-mild, 3-moderate, 4-severe. Day 1 was Baseline and Change from Baseline was calculated by subtracting Baseline value from value at specified time points (Week 1, 2, 4, 8, and 12). | Baseline (Day 1) and Week 1, 2, 4, 8 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clindamycin (CLDM), twice daily, once daily, CLDM 1%-BPO 3% gel, benzoyl peroxide (BPO), inflammatory lesion, non-inflammatory lesion, acne vulgaris