Study STF115288, a Clinical Confirmation Study of GI148512 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, double-blinded, vehicle-controlled, parallel-group study in Japanese subjects with acne vulgaris to demonstrate the efficacy of GI148512 (benzoyl peroxide [BPO] 3% gel) when applied once daily for 12 weeks. This study will also evaluate the safety of GI148512 when applied topically once 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 objective is to demonstrate the superiority of GI148512 to vehicle gel in total lesion counts. The secondary objectives are to demonstrate the superiority of GI148512 to vehicle gel in inflammatory lesion counts, and to evaluate the efficacy of GI148512 compared with vehicle gel at each visit. A total of 360 subjects will be enrolled and randomly assigned to one of the groups.

Official Title
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Study STF115288, a Clinical Confirmation Study of GI148512 (Benzoyl Peroxide 3% Gel) in the Treatment of Acne Vulgaris in Japanese Subjects.- A Multicenter, Randomized, Double-blinded, Vehicle-controlled, Parallel-group Study -

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: GI148512
* Drug: vehicle gel


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 (global assessment of severity by the investigator: refer to Section 6.2.1 Assessment) 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. 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 intralesional 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GI148512 (Benzoyl Peroxide 3% Gel)<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. Comparison of 2 arms (GI148512 vs vehicle) | Drug: GI148512<br>* GI148512, Topical gel in 1 g containing benzoyl peroxide 30 mg<br>* Other names: Benzoyl Peroxide 3% Gel;|
| Placebo Comparator: vehicle gel<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: vehicle gel<br>* Matching vehicle gel of GI148512, not containing active ingredient (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 Counts From Baseline to Week 12 | The investigator (or subinvestigator) counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedos; diagnosis based on palpation) on the face at each study visit. An open comedo is 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 comedo is a closed follicle filled with impacted sebum covered by keratin that has a whitish color. A papule is a small, raised, red, dome-shaped palpable lesion. A pustule is a raised, dome-shaped palpable lesion containing yellow fluid (pus). A nodule may be a raised or deep-seated, dome-shaped palpable lesion of at least 5 millimeters in diameter. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Total Lesion Counts From Baseline to Weeks 1, 2, 4, and 8 | The investigator/subinvestigator counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedo) on the face at each study visit. An open comedo is 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 comedo is a closed follicle filled with impacted sebum covered by keratin that has a whitish color. A papule is a small, raised, red, dome-shaped palpable lesion. A pustule is a raised, dome-shaped palpable lesion containing yellow fluid (pus). A nodule may be a raised or deep-seated, dome-shaped palpable lesion of at least 5 millimeters in diameter.Data were analyzed using an ANCOVA model with terms for Baseline value, treatment, and center. | Baseline; Weeks 1, 2, 4, and 8 | 
| Absolute Change From Baseline in Inflammatory Lesion (IL) Count and Non-inflammatory Lesion (NIL) Count to Weeks 1, 2, 4, 8, and 12 | The investigator/subinvestigator counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedo) on the face at each study visit. An open comedo is 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 comedo is a closed follicle filled with impacted sebum covered by keratin that has a whitish color. A papule is a small, raised, red, dome-shaped palpable lesion. A pustule is a raised, dome-shaped palpable lesion containing yellow fluid (pus). A nodule may be a raised or deep-seated, dome-shaped palpable lesion of at least 5 millimeters in diameter. Data were analyzed using an ANCOVA model with terms for Baseline value, treatment, and center. | Baseline; Weeks 1, 2, 4, 8, and 12 | 
| Percent Change From Baseline in Total, Inflammatory, and Non-inflammatory Lesion Counts to Weeks 1, 2, 4, 8, and 12 | The percent change from Baseline to Weeks 1, 2, 4, 8, and 12 in lesion counts (total [inflammatory and non-inflammatory], inflammatory [IL], and non-inflammatory [NIL]) was analyzed using an ANOVA model with terms for treatment and center. Percent change from Baseline was calculated as: (post-Baseline value minus Baseline value) * 100. | Baseline; Weeks 1, 2, 4 and 8 and 12 | 
| Number of Participants Who Had a Minimum 2-grade Improvement in the Investigator's Static Global Assessment (ISGA) Score From Baseline to Week 12 | Investigators evaluated the acne severity of the participants' face using the ISGA scale, ranging from 0 to 5: 0=clear skin with no inflammatory lesions (ILs) or non-inflammatory lesions (NILs); 1=almost clear: rare NILs with no more than rare papules; 2=mild acne: greater than Grade 1, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate acne: greater than Grade 2, up to many NILs and had some ILs, but no more than one small NL; 4=severe acne: greater than Grade 3, up to many NILs and ILs, but no more than a few NLs; 5=very severe acne: many NILs and ILs and more than a few NLs, had cystic lesions. | Baseline and Week 12 | 
| Number of Participants Who Had an ISGA Score of 0 or 1 at Weeks 1, 2, 4, 8, and 12 | Investigators evaluated the acne severity of the participants' face using the ISGA scale, ranging from 0 to 5: 0=clear skin with no inflammatory lesions (ILs) or non-inflammatory lesions (NILs); 1=almost clear: rare NILs with no more than rare papules; 2=mild acne: greater than Grade 1, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate acne: greater than Grade 2, up to many NILs and had some ILs, but no more than one small NL; 4=severe acne: greater than Grade 3, up to many NILs and ILs, but no more than a few NLs; 5=very severe acne: many NILs and ILs and more than a few NLs, had cystic lesions. | Weeks 1, 2, 4, 8, and 12 | 
| Number of Participants Who Had a Reduction in Total Lesions of at Least 50% From Baseline to Weeks 1, 2, 4, 8, and 12 | The proportion of participants who have a reduction in total lesions (inflammatory and non-inflammatory) of at least 50% from Baseline at Weeks 1, 2, 4, 8, and 12 was measured. | Baseline; Weeks 1, 2, 4, 8, and 12 | 
| Mean Change From Baseline in Erythema, Dryness, and Peeling Scores at Weeks 1, 2, 4, 8, 12/Withdrawal | Erythema (redness), dryness, and peeling were evaluated independently by the investigator as: 0 (absent)=no erythema, dryness, or peeling; 1 (slight)=faint red/pink coloration, barely perceptible dryness with no flakes or fissure, mild localized peeling; 2 (mild)=light red/pink coloration, perceptible dryness with no flakes/fissure, mild and diffuse peeling; 3 (moderate)=medium red coloration, easily noted dryness and flakes but no fissure, moderate and diffuse peeling; 4 (severe)=beet red coloration, dryness with flakes and fissure, prominent dense peeling. Change from Baseline was calculated as the post-Baseline/Withdrawal value minus the Baseline value. | Baseline; Weeks 1, 2, 4, 8, 12 or Withdrawal | 
| Mean Change From Baseline in Itching and Burning/Stinging Scores at Weeks 1, 2, 4, 8, 12/Withdrawal | Itching and burning/stinging were evaluated by the participant as: 0 (none)=normal, no discomfort; 1 (slight)=noticeable discomfort that caused intermittent awareness; 2 (mild)=noticeable discomfort that caused continuous awareness; 3 (moderate)=noticeable discomfort that caused intermittent awareness and interfered occasionally with normal daily activities; 4 (severe)=definite continuous discomfort that interfered with normal daily activities. Change from Baseline was calculated as the post-Baseline/Withdrawal value minus the Baseline value. | Baseline; Weeks 1, 2, 4, 8, 12 or withdrawal | 

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