Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of an approximate 1.5 mg/kg/day dose of oral sarecycline compared to placebo in the treatment of moderate to severe facial acne vulgaris

Official Title
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A Randomized, Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of 1.5 mg/kg Per Day of Sarecycline Compared to Placebo in the Treatment of Acne Vulgaris

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Sarecycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent or assent form Male/female, 9 to 45 years of age, inclusive Body weight between 33 and 136 kg, inclusive Facial acne vulgaris with: 20-50 inflammatory lesions (papules, pustules and nodules) 30-100 noninflammatory lesions (open and closed comedones) No more than 2 nodules Investigator's Global Assessment (IGA) score of moderate (3) or severe (4) Negative urine pregnancy test at baseline - females of childbearing potential Agrees to use an effective method of contraception throughout the study Refrain from use of any other acne medications and medicated cleansers, and avoid excessive sun exposure and tanning booths for duration of study Able to fulfill the requirements of protocol, indicated willingness to participate in the study and agrees to all study procedures (including mandatory photography) by providing written informed consent/assent and an authorization to disclose protected health information (PHI). Exclusion Criteria: Has a dermatological condition of the face that could interfere with the clinical evaluations Has a history of any of the following: Allergy to tetracycline-class antibiotics or to any ingredient in the study drug Pseudomembranous colitis or antibiotic-associated colitis Treated for any type of cancer within the last 6 months Has known resistance to other tetracyclines Has receive any of the following treatments within 12 weeks of screening: Systemic retinoids Systemic corticosteroids Androgens/anti-androgenic therapy (eg, anabolic steroids, spironolactone) Non-medicated procedures for the treatment of acne (eg, laser, light or ThermaClear) Has used any acne affecting treatment without an appropriate washout period Has initiated hormonal contraceptive use within 12 weeks prior to screening or plans to initiate or switch hormonal contraceptive products during the study period Is pregnant, lactating or planning a pregnancy during the study period Has any other disorder causing hyperandrogenism including, but not limited to polycystic ovary syndrome, adrenal or ovarian tumors, Cushings disease or congenital adrenal hyperplasia Has drug-induced acne Has significant intercurrent illness, psychiatric disposition or other factors that, in the opinion of the Investigator or Medical Monitor, precludes participation in the study Is currently participating, or has participated within 30 days prior to the screening period in an investigational drug or device study Has previously participated in any clinical trial involving the use of sarecycline Is judged by the Investigator to be unsuitable for any reason.

Ages Eligible for Study
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Minimum Age: 9 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: Sarecycline<br>Sarecycline tablets, 1.5 milligram(mg)/kilogram(kg)/day, taken orally once daily for 12 weeks. | Drug: Sarecycline<br>* 1.5 mg/kg/day taken orally at the same time each day.<br>|
| Placebo Comparator: Placebo<br>Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks. | Drug: Placebo<br>* Placebo-matching sarecycline tablets, taken orally at the same time each day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 12 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 centimeter (cm) in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 12 | 
| Percentage of Participants With Investigator's Global Assessment (IGA) Scale Success at Week 12 | The investigator assessed the participant's inflammatory lesions on the face using the IGA 5-point scale. The scale ranges from 0 (best): clear, no evidence of papules or pustules to 4 (worst): severe, inflammatory lesions are more apparent, many papules/pustules, there may or may not be a few nodulocytic lesions. Success was defined as at least a 2-point decrease (improvement) from Baseline on the IGA assessment as well as a score of clear (0) or almost clear (1). The percentage of participants who achieved success is reported. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 12 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Facial inflammatory lesions (pustules, papules, and nodular lesions) were counted and recorded separately. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 12 | 
| Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 9 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Facial inflammatory lesions (pustules, papules, and nodular lesions) were counted and recorded separately. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 9 | 
| Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 6 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Facial inflammatory lesions (pustules, papules, and nodular lesions) were counted and recorded separately. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 6 | 
| Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 3 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Facial inflammatory lesions (pustules, papules, and nodular lesions) were counted and recorded separately. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 3 | 
| Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 9 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Facial inflammatory lesions (pustules, papules, and nodular lesions) were counted and recorded separately. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 9 | 
| Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 6 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Facial inflammatory lesions (pustules, papules, and nodular lesions) were counted and recorded separately. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 6 | 
| Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 3 | Facial area lesion counts were made at the forehead, left and right cheeks, nose, and chin at baseline and at each treatment period visit. Facial inflammatory lesions (pustules, papules, and nodular lesions) were counted and recorded separately. Inflammatory lesion counts were based on the following definitions: papule: a solid, elevated lesion < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; pustule: an elevated lesion containing pus < 0.5 cm in diameter (by inspection) with surrounding erythematous halo; nodule: palpable solid erythematous lesion > 0.5 cm in diameter (by inspection); has depth, not necessarily elevated. A negative change from Baseline indicates that the number of inflammatory lesions decreased. Analyses were based on analysis of covariance (ANCOVA) model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate. | Baseline (Day 1) to Week 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acne