Randomized, Double-blind, Placebo-controlled Study to Eva... | NCT02322866

Name	Class
Allergan	INDUSTRY

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

Name	Type	Description	Arm Group Labels	Other Names
Sarecycline	Drug	1.5 mg/kg/day taken orally at the same time each day.	Sarecycline

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

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
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.

Name	Affiliation	Role
David Berk, MD	Allergan, plc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Warner Chilcott Research Site (Site #206)		Mobile	Alabama	36608	United States
Warner Chilcott Research Site (Site #236)

ID	Title	Description
FG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
FG001	Sarecycline	Sarecycline tablets, 1.5 milligram(mg)/kilogram(kg)/day, taken orally once daily for 12 weeks.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

lesion count

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Units	Counts
Participants	OG000515 OG001519

Title

Denominators

Categories

Title	Measurements
	OG000-10.7± 0.5 OG001-15.1± 0.6

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		< 0.0001	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.	Least Squares Mean Difference	-4.4			2-Sided	95	-5.8	-2.9			sarecycline - placebo		Superiority

Primary

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.

ITT Population included all randomized participants.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Units	Counts

Secondary

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.

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

percent change in lesion counts

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Secondary

Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 9

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

percent change in lesion counts

Baseline (Day 1) to Week 9

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Secondary

Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 6

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

percent change in lesion counts

Baseline (Day 1) to Week 6

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Secondary

Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 3

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

percent change in lesion counts

Baseline (Day 1) to Week 3

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Secondary

Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 9

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

lesion count

Baseline (Day 1) to Week 9

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Secondary

Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 6

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

lesion count

Baseline (Day 1) to Week 6

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

Secondary

Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 3

ITT Population included all randomized participants.

Posted

Least Squares Mean

Standard Error

lesion count

Baseline (Day 1) to Week 3

ID	Title	Description
OG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
OG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	0	513	1	513	0	513
EG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.	0	513	4	513	0	513

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Crohn's disease	Gastrointestinal disorders	MedDRA, Version 19.1	Systematic Assessment	EG0000 affected513 at risk EG0011 affected513 at risk
Tonsillitis	Infections and infestations	MedDRA, Version 19.1	Systematic Assessment	EG0000 affected513 at risk EG0011 affected513 at risk
Abortion	Pregnancy, puerperium and perinatal conditions	MedDRA, Version 19.1	Systematic Assessment	EG0000 affected513 at risk EG0011 affected513 at risk
Depression	Psychiatric disorders	MedDRA, Version 19.1	Systematic Assessment	EG0000 affected513 at risk EG0011 affected513 at risk
Oppositional defiant disorder	Psychiatric disorders	MedDRA, Version 19.1	Systematic Assessment	EG0001 affected513 at risk EG0010 affected513 at risk

ID	Term
D017486	Acneiform Eruptions
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D012625	Sebaceous Gland Diseases

ID	Title	Description
BG000	Placebo	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.
BG001	Sarecycline	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
BG002	Total	Total of all reporting groups