Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne

• ClinicalTrials.gov Identifier: NCT02320149
• Recruitment Status: Completed
• First Posted: December 19, 2014
• Results First Posted: May 17, 2018
• Last Update Posted: February 15, 2019
• Sponsor: Almirall, S.A.
• Collaborator: Allergan
• Information provided by (Responsible Party): Almirall, S.A.

Tracking Information

• First Submitted Date: December 15, 2014
• First Posted Date: December 19, 2014
• Results First Submitted Date: April 17, 2018
• Results First Posted Date: May 17, 2018
• Last Update Posted Date: February 15, 2019
• Actual Study Start Date: December 18, 2014
• Actual Primary Completion Date: February 1, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2018)

• Absolute Change in Facial Inflammatory Lesion Counts at Week 12 [ Time Frame: Baseline (Day 1) to 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.
• Percentage of Participants With Investigator Global Assement (IGA) Success at Week 12 [ Time Frame: Baseline (Day 1) to 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.

Original Primary Outcome Measures (submitted: December 18, 2014)

• Absolute Change in Inflammatory Lesion Count [ Time Frame: Baseline to week 12 ]
• Investigator Global Assement (IGA) Success [ Time Frame: Baseline to week 12 ]
  Defined as at least a 2-point decrease from baseline and a score of clear/0 or almost clear/1

• Change History: Complete list of historical versions of study NCT02320149 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: April 17, 2018)

• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 12 [ Time Frame: Baseline (Day 1) to 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 ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 9 [ Time Frame: Baseline (Day 1) to 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. 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 ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 6 [ Time Frame: Baseline (Day 1) to 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. 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 ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 3 [ Time Frame: Baseline (Day 1) to 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. 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 ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 9 [ Time Frame: Baseline (Day 1) to 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. 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 ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 6 [ Time Frame: Baseline (Day 1) to Weeks 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. 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 ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 3 [ Time Frame: Baseline (Day 1) to 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. 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 ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Percent Change From Baseline in Facial Noninflammatory Lesion Counts at Week 12 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Percent Change From Baseline in Facial Noninflammatory Lesion Counts at Week 9 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Percent Change From Baseline in Facial Noninflammatory Lesion Counts at Week 6 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Percent Change From Baseline in Facial Noninflammatory Lesion Counts at Week 3 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Absolute Change From Baseline in Facial Noninflammatory Lesion Counts at Week 12 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Absolute Change From Baseline in Facial Noninflammatory Lesion Counts at Week 9 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Absolute Change From Baseline in Facial Noninflammatory Lesion Counts at Week 6 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
• Absolute Change From Baseline in Facial Noninflammatory Lesion Counts at Week 3 [ Time Frame: Baseline (Day 1) to 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. Noninflammatory lesion counts were based on the following definitions: open comedones (blackheads): noninfected plugged hair follicle with a dilated/open orifice, black in color; closed comedones (whiteheads): noninfected plugged hair follicle with a small (microscopic) opening at the surface of the skin. A negative change from Baseline indicates that the number of noninflammatory lesions decreased. Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.

• Original Secondary Outcome Measures (submitted: December 18, 2014): Percent Change in Inflammatory Lesion Counts [ Time Frame: Baseline to week 12 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne
• Official Title: A Randomized, Multicenter, Double-blind, Placebocontrolled 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
• Brief Summary: To evaluate the efficacy and safety of an approximate 1.5mg/kg/day dose of oral sarecycline compared to placebo in the treatment of moderate to severe facial acne vulgaris
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Acne Vulgaris

Intervention

• Drug: Sarecycline
  1.5 mg/kg/day taken orally at the same time each day,
• Drug: Placebo
  Placebo-matching sarecycline tablets taken orally at the same time each day.

Study Arms

• Experimental: Sarecycline
  Sarecycline tablets, 1.5 milligram(mg)/kilogram(kg)/day, taken orally once daily for 12 weeks.
  Intervention: Drug: Sarecycline
• Placebo Comparator: Placebo
  Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 15, 2017): 968
• Original Estimated Enrollment (submitted: December 18, 2014): 1000
• Actual Study Completion Date: February 1, 2017
• Actual Primary Completion Date: February 1, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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
• 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 received 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 9 Years to 45 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02320149
• Other Study ID Numbers: SC1401
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Almirall, S.A.
• Study Sponsor: Almirall, S.A.
• Collaborators: Allergan

Investigators

• Study Director: Alexandre Kaoukhov, MD; Warner Chilcott, an Affiliate of Allergan plc

• PRS Account: Almirall, S.A.
• Verification Date: January 2019