Comparison of the Efficacy and Safety of Clindamycin + Benzoyl Peroxide Formulation With Azelaic Acid Formulation in the Treatment of Acne Vulgaris

Study Overview
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Brief Summary
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This is a randomized, comparator-controlled, single-blind, parallel-group study. The current study proposes to compare a fixed-dose combination product containing 3% benzoyl peroxide (BPO) and 1% clindamycin against a cream containing 20% azelaic acid for the treatment of facial acne vulgaris. The results of the study will enable a better assessment of the safety and efficacy of the new dose regime (BPO 3% + clindamycin 1%) in comparison to a well established treatment. Based on the data more evidence based recommendations will be possible to improve the treatment of subjects with acne vulgaris. A total of 220 subjects will be enrolled and will have 5 study visits (Day 1, Weeks 2, 4, 8 and 12). The duration of the study will be over 12 weeks.

Official Title
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A Multi-centre, Single-blind, Parallel Group, Clinical Evaluation of the Efficacy and Safety of Clindamycin 1% / Benzoyl Peroxide 3% and Azelaic Acid 20% in the Topical Treatment of Mild to Moderate Acne Vulgaris

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Clindamycin + BPO
* Drug: Azelaic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are males or females 12 to 45 years of age, inclusive. Subjects with acne vulgaris who have: a minimum of 17 to a maximum of 60 inflammatory facial lesions (papules and pustules), including the nose, and no more than 1 facial nodular cystic lesions and a minimum of 20 to a maximum of 125 non-inflammatory facial lesions (open and closed comedones) and an ISGA score of 2 or 3. Subjects agreeing not to use sun-beds or undergo any ultraviolet (UV) light treatment for 4 weeks prior to entering the study and to minimize the amount of exposure to direct sunlight for the duration of the study. Subjects who are capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol-specific procedures are performed. Subjects under the legal age of consent must provide assent and have the written, informed consent of both parents or legal guardians. Exclusion Criteria: Unable to comply with the requirement of the study. Female subjects who are pregnant, breast-feeding, or sexually active and not using reliable contraception and/or not prepared to do so for the duration of the trial (a negative pregnancy test must be confirmed at Visit 1, 3, 4 and 5, for all females if menarche has occurred). 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 obscure the accurate assessment of acne grade. Subjects who have a history or presence of regional enteritis or inflammatory bowel disease (eg, ulcerative colitis, pseudomembranous colitis, chronic diarrhea, or a history of antibiotic-associated colitis) or similar symptoms. Prior Therapy: Have received treatment with the following therapies at the times specified prior to Baseline: systemic retinoids [6 months]; systemic antibiotics, investigational therapy, facial procedure (chemical or laser peel, microdermabrasion, artificial UV therapy), topical corticosteroids on the face or systemic corticosteroids [4 weeks]; topical antibiotics on the face, topical anti-acne medications (eg, BPO, retinoids, azelaic acid, resorcinol, salicylates, sulfacetamide sodium and derivatives, glycolic acid) [2 weeks]; medications that are reported to exacerbate acne (eg, mega-doses of certain vitamins such as vitamin D, vitamin A, and vitamins B2, B6, and B12; haloperidol; halogens such as iodide and bromide; lithium; hydantoin; and phenobarbital) as these may impact efficacy assessments, neuromuscular blocking agents (Clindamycin has neuromuscular blocking activities, which may enhance the action of other neuromuscular blocking agents), drugs known to be photosensitizers (eg, thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the possibility of increased phototoxicity [1 day]. Subjects who are unwilling to stop using the following types of facial products during the study: astringents, toners, abradants, facials, peels containing glycolic or other acids, masks, washes or soaps containing BPO, sulfacetamide sodium or salicylic acid, non-mild facial cleansers, or moisturizers that contain retinol, salicylic acid, or alpha- or beta-hydroxy acids. Subjects who have a known hypersensitivity or previous allergic reaction to any of the active components (azaleic acid, lincomycin, clindamycin, BPO), or excipients of the study medication. Use of estrogens, including oral, implanted, and topical contraceptives, androgens, or anti-androgenic agents of less than 12 consecutive weeks prior to start of study dosing (change of the dose or drug is not permitted between 12 weeks prior study dosing until end of 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: Arm 1<br>A total of 110 subjects will receive clindamycin + BPO once daily in the evening for 12 weeks as per the randomization schedule. | Drug: Clindamycin + BPO<br>* Gel containing 1.2% clindamycin and 3% BPO for once daily application<br>|
| Experimental: Arm 2<br>A total of 110 subjects will receive azelaic acid twice daily (1 in the morning and 1 in the evening) for 12 weeks as per the randomization schedule. | Drug: Azelaic acid<br>* Cream containing 20% azelaic acid for twice daily application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline (Day 1) of Inflammatory Lesion (IL) Count at Week 4 - Superiority Analysis | A count of IL (papules and pustules, including nasal lesions) was performed at baseline and up to Week 12. Lesion counts were confined to the face. Baseline was defined at Visit 1 (Day 1). Change from Baseline in the number of IL was defined as Week 4 values minus the Baseline values. Raw data has been presented for outcome measure results; however, p value is derived from the Wilcoxon test mean scores. | Baseline (Day 1) and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in IL, Non-inflammatory Lesions (NIL) and Calculated Total Lesions to Weeks 2, 4, 8 and 12 | A count of IL (papules and pustules, including nasal lesions), NIL (open and closed comedones) and total lesions was performed at baseline and up to Week 12. Lesion counts were confined to the face. Baseline was defined at Visit 1 (Day 1). Change from Baseline in the number of IL was defined as week 12 values minus the Baseline values. | Baseline (Day 1) up to Week 2, 4, 8, 12 | 
| Percentage Change From Baseline in IL, NIL and Calculated Total Lesions at Weeks 2, 4, 8 and 12 | A count of IL (papules and pustules, including nasal lesions),NIL (open and closed comedones) and total lesions was performed at baseline and up to Week 12. Lesion counts were confined to the face. Baseline was defined at Visit 1 (Day 1). Change from Baseline in the number of IL was defined as week 12 values minus the Baseline values. | Baseline (Day 1) up to Week 2, 4, 8, 12 | 
| Speed of Onset : Time to 50 Percent Reduction in Total Lesion Count | The average time to 50 percent reduction of the calculated total lesion count was analyzed by determination of the number of days between Baseline and the first visit with a 50 percent reduction of the count. | Week 12 | 
| Number of Participants With Change From Baseline in Investigator's Static Global Assessment (ISGA) to Weeks 2,4,8 and 12 | ISGA was conducted at all study visits. The area considered for the ISGA was confined to the face. A 0-5 point rating scale was used: 0 means Clear- Clear skin with no IL or NIL, 1 means Almost Clear- Rare NIL with no more than one small IL, 2 means Mild- Some NIL with no more than a few IL (papules/pustules only, no nodular lesions), 3 means Moderate- Up to many NIL and may have some IL, but no more than one small nodular lesion, 4 means Severe- Up to many NIL and IL, but no more than a few nodular lesions and 5 means Very Severe- Many NIL and IL and more than a few nodular lesions, may have cystic lesions. | Baseline (Day 1) up to Weeks 2, 4, 8, 12 | 
| Number of Participants With Change From Baseline in Local Tolerability as Per Investigator's Assessment at Weeks 2,4,8,12 | Tolerability was assessed by investigator on a 0-3 point rating scale for erythema (0- None, 1- Slight, 2- Some and 3- Very red), dryness (0- None, 1- Slight, 2- Some and 3- Very dry) and peeling (0- None, 1- Slight, 2- Moderate and 3- Strong). A shift table was provided to deduce how the results are varying from the baseline visit to post-baseline visits. Change from Baseline is the value at indicated time point minus the Baseline value. | Baseline (Day 1) and Weeks 2, 4, 8, 12 | 
| Number of Participants With Participant Global Change Assessment Score 12 Weeks | An SGCA was conducted by the participant to assess the efficacy of treatment on Week 2, 4, 8 and 12 as Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse, Very Much Worse and missing. | Weeks 2, 4, 8 and 12 | 
| Number of Participants With Change From Baseline in Local Tolerability as Per Participant's Assessment at Weeks 2, 4, 8 and 12 | Tolerability was assessed by the participants based on a 0-3 point rating scale for stinging/burning (S/B) and pruritus of the face (0- None, 1- Slight, 2- Moderate and 3- Strong). A shift table was provided to deduce how the results are varying from the Baseline visit to post-baseline visits. | Baseline (Day 1), Weeks 2, 4, 8 and 12 | 
| Number of Participants With Participant Satisfaction Score at Week 12 (Simple Grading) | The product acceptability and preference questionnaire (PAP-Q ) served as a patient satisfaction score and was performed only once at the final study visit (ie, after 12 weeks (V5) or earlier in case of premature termination). Severity of each facial acne sign and symptom (scaling, redness, dryness, burning, itching) was based on a 0-5 point rating scale (0- None, 1- Very minimal, 2- Mild, 3- Moderate, 4- Severe, 5- Very severe). | Week 12 | 
| Number of Treatment Adherent Participants at Week 12 | The general assessment of 'overall satisfaction' with study therapy was assessed at week 12 on a 0-4 point rating scale (0-Very satisfied, 1- Satisfied, 2- Neutral, 3- Unsatisfied and 4- Very unsatisfied). | Week 12 | 
| Absolute Change From Baseline in Total Score as Per Dermatology Life Quality Index (DLQI) at Week 2,4,8 and 12 | This outcome measure was a measure of quality of life (QOL). The DLQI was used to assess the quality of life at each visit. Participants completed the questionnaire to evaluate how their acne has affected their life. The DLQI is a 10 item questionnaire, which addresses feelings, daily activities, leisure, work, school, personal relationships, and treatment. Each question was scored out of 0-3, as follows: 0- Not at all, 1- A little, 2- A lot, 3- very much, indicating 0 as the least and 3 as the best quality Index. The sub-scale scores of 10 questions were combined and a composite score was presented. The total score ranged from 0 to 30, 0 indicated the least and highest score indicated the best quality Index. The DLQI was for participants with 17 to 45 years of age. Baseline was defined at Visit 1 (Day 1). Change from Baseline is the value at indicated time point minus the Baseline value. | Baseline (Day 1) up to Weeks 2, 4, 8, 12 | 
| Absolute Change From Baseline in Total Score as Per Children's Dermatology Life Quality Index (CDLQI) at Week 2,4,8 and 12 | This outcome measure was a measure of QOL. The CDLQI was used to assess the quality of life at each visit. Participants completed the questionnaire to evaluate how their acne has affected their life. The DLQI is a 10 item questionnaire, which addresses feelings, daily activities, leisure, work, school, personal relationships, and treatment. Each question was scored out of 0-3, as follows: 0- Not at all, 1- A little, 2- A lot, 3- very much, indicating 0 as the least and 3 as the best quality Index. The sub-scale scores of 10 questions were combined and a composite score was presented. The total score ranged from 0 to 30, 0 indicated the least and highest score indicated the best quality Index. The CDLQI was for participants with 12 to 16 years of age. Baseline was defined at Visit 1 (Day 1). Change from Baseline is the value at indicated time point minus the Baseline value. | Baseline (Day 1) up to Weeks 2, 4, 8, 12 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) Related to Study Medication | Adverse events are defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious adverse events are defined as any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect and medically significant. TEAEs and TESAEs were reported up to 12 weeks. | Up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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azelaic acid, Clindamycin, Benzoyl peroxide, Acne vulgaris