DUAC® Early Onset Efficacy Study in Japanese Subjects

Study Overview
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Brief Summary
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This is a multicentre, randomized, single-blind (investigator is blinded), active (the combination therapy of adapalene [ADA] and clindamycin [CLDM])-controlled and parallel-group study in Japanese subjects with facial acne vulgaris. The purpose of this study is to evaluate the efficacy, safety and tolerability of CLDM 1 percent (%)-benzoyl peroxide 3% (Duac®: trademark owned by GlaxoSmithKline) once daily fixed dose combination gel versus combination therapy of ADA 0.1% gel and CLDM 1% gel in the topical treatment of facial acne vulgaris for 12 weeks. A total of 400 subjects will be screened for enrolment. Subjects will use Duac® fixed dose combination gel with quantity sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) or combination therapy of ADA 0.1% gel with quantity sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) and CLDM 1% gel twice daily, once in the morning and once in the evening (at bedtime) for 12 weeks.

Detailed Description
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Duac® is a registered trademark of Stiefel Laboratories, Inc., a GSK company. Duac® marketed in Japan is CLDM 1%-benzoyl peroxide 3% combination gel.

Official Title
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Clinical Evaluation of Efficacy at 2 Weeks of Duac® Fixed Dose Combination Gel in Treatment of Facial Acne Vulgaris in Japanese Subjects

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Duac® fixed dose combination gel
* Drug: ADA 0.1% gel
* Drug: CLDM 1% gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between 12 to 45 years of age, inclusive. Subjects must have had both: (a) A minimum of 17 but not more than 60 ILs (papules / pustules) on the face, including nasal lesions; (b) A minimum of 20 but not more than 150 non-ILs (open / closed comedones) on the face, including nasal lesions. Subjects who have an ISGA score of 2 or greater at Baseline. Female subjects of childbearing potential and women who are less than 2 years from their last menses must agree to use contraception Subjects who are willing and able to follow all study procedures and to visit all scheduled evaluation points. Subjects who have ability to understand and give a written informed consent form (written informed consent must be obtained also from the parent or guardian if the participant is under 20 years of age). Exclusion Criteria: Subjects who have any nodulo-cystic lesions at Baseline. Female subjects who are pregnant or who are breast-feeding. Subjects who have a history or presence of regional enteritis, inflammatory bowel disease (e.g. ulcerative colitis, pseudomembranous colitis, chronic diarrhoea, antibiotic-associated colitis or bloody diarrhoea) or similar symptoms. Subjects who used any of the following agents within 2 weeks prior to Baseline: topical antibiotics on the face or systemic antibiotics; topical anti-acne medications (e.g. Benzoyl peroxide, azelaic acid, resorcinol, salicylates etc.); abradants, facials, peels, masks containing glycolic or other acids; washes, soaps, non mild facial cleansers containing benzoyl peroxide, salicylic acid or sulfacetamide sodium; moisturizers containing retinol, salicylic acid or alpha or beta-hydroxy acids (except additive agent); astringents and toner. Subjects who used any of the following agents on the face or performed the following procedure within 4 weeks prior to baseline: topical corticosteroids applied onto face (use of inhaled, intra-articular or intra-lesional steroids other than for facial acne is acceptable); facial procedure (such as chemical and laser peel, microdermabration, blue light treatment, etc.). Subjects who used systemic retinoids within the previous 6 months or topical retinoids within 6 weeks prior to Baseline. Subjects who 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). Subjects who are using any medication that in the opinion of the investigator may affect this clinical study or evaluation of the study. Subjects who plan to use medications that are reported to exacerbate acne (such as vitamin D and vitamin B12, corticosteroids, androgens, haloperidol, halogens, lithium, hydantoin and Phenobarbital). Subjects who have a known hypersensitivity or have had previous allergic reaction to any of the components of the investigational product. Subjects who have used investigate therapy within the previous 12 weeks or plan to participate in another clinical study at the same time. Subjects who participated in another Japanese clinical study planned by GlaxoSmithKline K.K. in the development of investigational products for acne vulgaris. Subjects with a history of substance abuse (alcohol or drugs) or substance dependence within 12 months prior to screening. Subjects who have medical history suggestive of an immunocompromized status. Subjects who are employees of a GlaxoSmithKline, an investigator or clinical research organization involved in the study or any immediate family member of an employee involved in the study. Subjects who have any other condition 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: Duac® fixed dose combination gel<br>Subjects will use Duac® fixed dose combination gel (clindamycin phosphate 1.2% and benzoyl peroxide 3%) with quantity sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) for 12 weeks. | Drug: Duac® fixed dose combination gel<br>* Duac® fixed dose combination gel containing clindamycin phosphate 1.2% and benzoyl peroxide 3%.<br>|
| Active Comparator: Combination therapy: ADA 0.1% gel + CLDM 1% gel<br>Subjects will use combination therapy of ADA 0.1% gel with quantity sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) and subjects will also apply CLDM 1% gel twice daily, once in the morning and once in the evening (at bedtime) for 12 weeks. The CLDM 1% gel should apply subsequent to the application of ADA 0.1% gel in the evening. The CLDM 1% gel should be applied to ILs only. | Drug: ADA 0.1% gel<br>* ADA 0.1% gel containing 0.1% of adapalene.<br>Drug: CLDM 1% gel<br>* CLDM 1% gel containing clindamycin phosphate 1.2% (1% as clindamycin).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Total Lesion Counts (TLs) From Baseline to Week 2 | The assessor performed a count of IL (papules, pustules, nodular lesions), non-ILs (open and closed comedones) and total lesions (the sum of IL and non-IL) at each study visit. Lesion counts were confined to the face. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. Data for adjusted mean has been reported. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100. The Baseline value was the latest pre-dose assessment value. The non-inflammatory lesions were counted by diagnosis based on palpation of the investigator (or sub-investigator). | Baseline (Day 1) and Week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in TLs to Weeks 1, 4, 8 and 12 | The assessor performed a count of IL (papules, pustules, nodular lesions), non-ILs (open and closed comedones) and total lesions (the sum of IL and non-IL) at each study visit. Lesion counts were confined to the face. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. Data for adjusted mean has been reported. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100. The Baseline value was the latest pre-dose assessment value. The non-ILs were counted by diagnosis based on palpation of the investigator (or sub-investigator). A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM. | Baseline (Day 1) and Week 1, 4, 8, 12 | 
| Percent Change Form Baseline in Lesion Counts (ILs and Non-ILs) to Weeks 1, 2, 4, 8 and 12 | The assessor performed a count of IL (papules, pustules, nodular lesions), non-ILs (open and closed comedones). Lesion counts were confined to the face. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. Data for adjusted mean has been reported. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100. The Baseline value was the latest pre-dose assessment value. The non-ILs were counted by diagnosis based on palpation of the investigator (or sub-investigator). | Baseline (Day 1) and Week 1, 2, 4, 8, 12 | 
| Absolute Change From Baseline in Lesion Counts (TLs, ILs and Non-ILs) to Weeks 1, 2, 4, 8 and 12 | The assessor performed a count of IL (papules, pustules, nodular lesions), non-ILs (open and closed comedones) and total lesions (the sum of IL and non-IL) at each study visit. Lesion counts were confined to the face. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. Data for adjusted mean has been reported. The non-ILs were counted by diagnosis based on palpation of the investigator (or sub-investigator). A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM. The Baseline value was the latest pre-dose assessment value. | Baseline (Day 1) and Week 1, 2, 4, 8, 12 | 
| Percentage of Participants With a Minimum of 2-grade Improvement in Investigator's Static Global Assessment (ISGA) Score From Baseline to Weeks 1, 2, 4, 8 and 12 | Responder was defined as participants with a minimum 2-grade improvement in ISGA score from Baseline. ISGA scale was scored from 0-5 (0= Clear skin with no inflammatory or non-ILs, 1= Almost clear: rare non-ILs present, with no more than rare papules, 2= Mild severity: greater than Grade 1, some non-ILs with no more than few inflammatory lesions, 3= Moderate severity: greater than Grade 2, many non-ILS, may have some ILs, but no more than 1 small nodular lesion, 4= Severe: greater than Grade 3, up to many non-ILs and ILs, but no more than a few nodular lesions, 5= Very severe: many non -ILs and ILs and more than a few nodular lesions. May have cystic lesions). Percentage of participants was calculated by dividing number of participants with 2-grade improvement in ISGA score from Baseline by total number of participants value multiplied by 100. | Week 1, 2, 4, 8, 12 | 
| Percentage of Participants With ISGA Score of 0 or 1 at Weeks 1, 2, 4, 8 and 12 | Responder was defined as participant with ISGA score of 0 or 1. ISGA scale was scored from 0-5 (0= Clear skin with no inflammatory or non-ILs, 1= Almost clear: rare non-ILs present, with no more than rare papules, 2= Mild severity: greater than Grade 1, some non-ILs with no more than few inflammatory lesions, 3= Moderate severity: greater than Grade 2, many non-ILS, may have some ILs, but no more than 1 small nodular lesion, 4= Severe: greater than Grade 3, up to many non-ILs and ILs, but no more than a few nodular lesions, 5= Very severe: many non -ILs and ILs and more than a few nodular lesions. May have cystic lesions). Percentage of participants was calculated by dividing number of participants with 0-1 ISGA score post Baseline by total number of participants value multiplied by 100. | Week 1, 2, 4, 8 and 12 | 
| Percentage of Participants With at Least 50% Reduction in Lesion Counts (TLs, ILs and Non-ILs) From Baseline at Weeks 1, 2, 4, 8 and 12 | Responder was defined as participants with at least a 50% reduction in TLs, ILs and non-ILs. Data for number of participants is reported. Percentage of participants was calculated by dividing number of responders by total number of participants value multiplied by 100. | Week 1, 2, 4, 8 and 12 | 
| Number of Participants With Treatment Adherence Rate at Weeks 1, 2, 4, 8 and 12 | The investigator (or sub-investigator), the product storage manager, or the blinded coordinator dispensed a study compliance log to record participant's compliance with investigational product application from Baseline to the end of study treatment. The product storage manager or the blinded coordinator evaluated the participant's compliance with study treatment, using the study compliance log at each visit, and recorded the compliance data in the eCRF. | Week 1, 2, 4, 8 and 12 | 
| Number of Participants Who Continued Treatment at Weeks 1, 2, 4, 8 and 12 | Number of participants who continued the treatment till Week 12 was measured. Overall data for participants who have not missed any dose during the treatment period has been reported. | Up to Week 12 | 
| Participant's Treatment Preference at Weeks 1, 2, 4, 8 and 12 | Participants had to rate each question on a 5-point scale of 0 to 4 (4: yes, very easy to use, 3: yes, easy, 2: slightly easy, 1: slightly difficult, 0: No) where larger score indicates more preferable participant's feeling. There were 5 questions in the questionnaire: ease of application, comfort, satisfaction with treatment (ST), comparison with prior therapies (CPT) and willingness to continue using the product (WCP). | Week 1, 2, 4, 8 and 12 | 
| Change From Baseline in Quality of Life (QoL) Score at Week 2, 4, 8 and 12 | QOL questionnaire was assessed using Skindex-16 with 16 questions in 3 multi-item scales: symptoms, emotions and functioning for the past week: skin condition-itching, burning or stinging, hurting, being irritated, persistence/reoccurrence of skin condition, worry about condition, appearance of skin, frustration about skin, embarrassment about skin, being annoyed about your skin, feeling depressed about skin, effects of your skin on your interactions with others, effects of your skin condition on your desire to be with people, skin condition making it hard to show affection, effects of your skin condition on your daily activities and skin condition making it hard to work or do what you enjoy. Data for adjusted mean has been reported. The Baseline value was the latest pre-dose assessment value. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. Scores range from 0-never bothered to 100-always bothered. | Baseline(Day 1) and Week 2, 4, 8 and 12 | 
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate. For liver injury and impaired liver function, alanine aminotransferase greater than or equal to (>=)3 times upper limit of normal (ULN) and total bilirubin >=2xULN (less than [>] 35% direct) was defined. | Up to Week 12 | 
| Local Tolerability Score for Erythema, Dryness, Peeling, Itching, and Burning or Stinging | Local tolerability score for erythema (no redness, faint red or pink coloration, barely perceptible, light red or pink coloration, medium red coloration, beet red coloration), dryness (none, barely perceptible dryness with no flakes or fissure formation, easily perceptible dryness with no flakes or fissure formation, easily noted dryness and flakes but no fissure formation, easily noted dryness with flakes and fissure formation), peeling (no peeling, mild localized peeling, mild and diffuse peeling, moderate and diffuse peeling, moderate to prominent, dense peeling) and itching and burning/stinging (normal-no discomfort, noticeable discomfort that causes intermittent awareness, continuous awareness, intermittent awareness and interferes occasionally with normal daily activities, a definite continuous discomfort that interferes with normal daily activities) was assessed on a scale of 0 to 4 (0= absent, 1= slight, 2= mild, 3= moderate and 4= severe). | Week 1, 2, 4, 8 and 12 | 
| Number of Participants With Severity of AEs | The severity of AEs was assessed by the investigator; events were assigned to one of the following categories: mild, an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate, an event that was sufficiently discomforting to interfere with normal everyday activities; and severe, an event that prevented normal everyday activities. | Up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clindamycin, Gel, Benzoyl Peroxide, Acne Vulgaris