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

• Sponsor: Almirall, S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02322866
• Collaborator: Allergan (Industry)
• Enrollment: 1,034
• Locations: 57
• Arms: 2
• Actual Duration (Months): 25.3
• Patients Per Site: 18.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acne Vulgaris	Drug: Sarecycline; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1034 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Dec 3, 2014
• Actual Primary Completion Date: Jan 12, 2017
• Actual Study Completion Date: Jan 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sarecycline Sarecycline tablets, 1.5 milligram(mg)/kilogram(kg)/day, taken orally once daily for 12 weeks.	Drug: Sarecycline; 1.5 mg/kg/day taken orally at the same time each day.
Placebo Comparator: Placebo Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Drug: Placebo; Placebo-matching sarecycline tablets, taken orally at the same time each day.

Outcome Measures

Primary Outcome Measures

1. Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 12 [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.

2. Percentage of Participants With Investigator's Global Assessment (IGA) Scale Success at Week 12 [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.

Secondary Outcome Measures

1. Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 12 [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. 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.

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

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

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

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

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

7. Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 3 [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. 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 Criteria

Criteria

• Ages Eligible for Study: 9 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warner Chilcott Research Site (Site #206)	Mobile	Alabama	United States	36608
2	Warner Chilcott Research Site (Site #236)	Hot Springs	Arkansas	United States	71913
3	Warner Chilcott Research Site (Site #245)	Carlsbad	California	United States	92008
4	Warner Chilcott Research Site (Site #234)	Encinitas	California	United States	92024
5	Warner Chilcott Research Site (Site #209)	Fremont	California	United States	94538
6	Warner Chilcott Research Site (Site #215)	Oceanside	California	United States	92056
7	Warner Chilcott Research Site (Site #204)	San Diego	California	United States	92123
8	Warner Chilcott Research Site (Site #254)	San Diego	California	United States	92123
9	Warner Chilcott Research Site (Site #257)	Santa Ana	California	United States	92701
10	Warner Chilcott Research Site (Site #243)	Santa Monica	California	United States	90404
11	Warner Chilcott Research Site (Site #222)	Denver	Colorado	United States	80220
12	Warner Chilcott Research Site (Site #237)	Aventura	Florida	United States	33180
13	Warner Chilcott Research Site (Site #226)	Clearwater	Florida	United States	33761
14	Warner Chilcott Research Site (Site #238)	Jupiter	Florida	United States	33458
15	Warner Chilcott Research Site (Site #255)	Lauderdale Lakes	Florida	United States	33319
16	Warner Chilcott Research Site (Site #249)	Miami	Florida	United States	33142
17	Warner Chilcott Research Site (Site #202)	Miami	Florida	United States	33144
18	Warner Chilcott Research Site (Site #211)	Miramar	Florida	United States	33027
19	Warner Chilcott Research Site (Site #247)	Ocala	Florida	United States	34471
20	Warner Chilcott Research Site (Site #241)	Orlando	Florida	United States	32806
21	Warner Chilcott Research Site (Site #228)	Pinellas Park	Florida	United States	33781
22	Warner Chilcott Research Site (Site #203)	Tampa	Florida	United States	33609
23	Warner Chilcott Research Site (Site #242)	Snellville	Georgia	United States	30078
24	Warner Chilcott Research Site (Site #210)	Champaign	Illinois	United States	61820
25	Warner Chilcott Research Site (Site #213)	Louisville	Kentucky	United States	40202
26	Warner Chilcott Research Site (Site #217)	Rockville	Maryland	United States	20850
27	Warner Chilcott Research Site (Site #248)	Watertown	Massachusetts	United States	02472
28	Warner Chilcott Research Site (Site #205)	Bay City	Michigan	United States	48706
29	Warner Chilcott Research Site (Site #251)	Clarkston	Michigan	United States	48346
30	Warner Chilcott Research Site (Site #235)	Clinton Township	Michigan	United States	48038
31	Warner Chilcott Research Site (Site #227)	Fort Gratiot	Michigan	United States	48059
32	Warner Chilcott Research Site (Site #221)	Fridley	Minnesota	United States	55432
33	Warner Chilcott Research Site (Site #231)	Omaha	Nebraska	United States	68144
34	Warner Chilcott Research Site (Site #253)	Newington	New Hampshire	United States	03801
35	Warner Chilcott Research Site (Site #239)	Albuquerque	New Mexico	United States	87106
36	Warner Chilcott Research Site (Site #208)	New York	New York	United States	10155
37	Warner Chilcott Research Site (Site #240)	Rochester	New York	United States	14623
38	Warner Chilcott Research Site (Site #230)	Stony Brook	New York	United States	11790
39	Warner Chilcott Research Site (Site #229)	Raleigh	North Carolina	United States	27612
40	Warner Chilcott Research Site (Site #250)	Wilmington	North Carolina	United States	28405
41	Warner Chilcott Research Site (Site #218)	Beachwood	Ohio	United States	44122
42	Warner Chilcott Research Site (Site #256)	Philadelphia	Pennsylvania	United States	19103
43	Warner Chilcott Research Site (Site #214)	Warwick	Rhode Island	United States	02886
44	Warner Chilcott Research Site (Site #219)	Fountain Inn	South Carolina	United States	29644
45	Warner Chilcott Research Site (Site #225)	Goodlettsville	Tennessee	United States	37072
46	Warner Chilcott Research Site (Site #216)	Knoxville	Tennessee	United States	37922
47	Warner Chilcott Research Site (Site #252)	Arlington	Texas	United States	76011
48	Warner Chilcott Research Site (Site #220)	College Station	Texas	United States	77845
49	Warner Chilcott Research Site (Site #201)	Katy	Texas	United States	77494
50	Warner Chilcott Research Site (Site #223)	Pflugerville	Texas	United States	78660
51	Warner Chilcott Research Site (Site #207)	San Antonio	Texas	United States	78218
52	Warner Chilcott Research Site (Site #224)	Webster	Texas	United States	77598
53	Warner Chilcott Research Site (Site #212)	West Jordan	Utah	United States	84088
54	Warner Chilcott Research Site (Site #244)	Norfolk	Virginia	United States	23507
55	Warner Chilcott Research Site (Site #246)	Seattle	Washington	United States	98105
56	Warner Chilcott Research Site (Site #233)	Walla Walla	Washington	United States	99362
57	Warner Chilcott Research Site (Site #232)	Madison	Wisconsin	United States	53719

Sponsors and Collaborators

• Almirall, S.A.
• Allergan

Investigators

• Study Director: David Berk, MD, Allergan, plc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Almirall, S.A.
• ClinicalTrials.gov Identifier: NCT02322866
• Other Study ID Numbers: SC1402
• First Posted: Dec 23, 2014
• Last Update Posted: Feb 1, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Almirall, S.A.: acne
• Additional relevant MeSH terms: Acne Vulgaris; Sarecycline

Study Results

Participant Flow

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 milligram(mg)/kilogram(kg)/day, taken orally once daily for 12 weeks.
Period Title: Overall Study
STARTED	515	519
COMPLETED	444	433
NOT COMPLETED	71	86

Baseline Characteristics

Arm/Group Title	Placebo	Sarecycline	Total
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.	Total of all reporting groups
Overall Participants	515	519	1034
Age, Customized (participants) [Number]
≥9 and <12 years	4 0.8%	7 1.3%	11 1.1%
≥12 and <18 years	256 49.7%	227 43.7%	483 46.7%
≥18 years	255 49.5%	285 54.9%	540 52.2%
Sex: Female, Male (Count of Participants)
Female	292 56.7%	315 60.7%	607 58.7%
Male	223 43.3%	204 39.3%	427 41.3%

Outcome Measures

1. Primary Outcome

Title	Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 12
Description	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.
Time Frame	Baseline (Day 1) to Week 12

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [lesion count]	-10.7 (0.5)	-15.1 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -5.8 to -2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

2. Primary Outcome

Title	Percentage of Participants With Investigator's Global Assessment (IGA) Scale Success at Week 12
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Number [percentage of participants]	15.3 3%	22.6 4.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments	P-values were based on the test of general association between the response and treatment group using Cochran-Mantel-Haenszel test with pooled site as stratification factor.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment Rate Difference
	Estimated Value	7.30
	Confidence Interval	(2-Sided) 95%; 2.53 to 12.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

3. Secondary Outcome

Title	Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 12
Description	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.
Time Frame	Baseline (Day 1) to Week 12

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [percent change in lesion counts]	-35.4 (1.8)	-49.9 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments	Percent Change from Baseline to Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-14.4
	Confidence Interval	(2-Sided) 95%; -19.4 to -9.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

4. Secondary Outcome

Title	Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 9
Description	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.
Time Frame	Baseline (Day 1) to Week 9

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [percent change in lesion counts]	-31.9 (1.7)	-44.5 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments	Percent Change from Baseline to Week 9
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-12.6
	Confidence Interval	(2-Sided) 95%; -17.3 to -7.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

5. Secondary Outcome

Title	Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 6
Description	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.
Time Frame	Baseline (Day 1) to Week 6

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [percent change in lesion counts]	-27.3 (1.6)	-39.1 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments	Percent Change from Baseline to Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-11.8
	Confidence Interval	(2-Sided) 95%; -16.1 to -7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

6. Secondary Outcome

Title	Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 3
Description	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.
Time Frame	Baseline (Day 1) to Week 3

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [percent change in lesion counts]	-18.6 (1.6)	-28.0 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments	Percent Change from Baseline to Week 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-9.4
	Confidence Interval	(2-Sided) 95%; -13.5 to -5.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

7. Secondary Outcome

Title	Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 9
Description	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.
Time Frame	Baseline (Day 1) to Week 9

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [lesion count]	-9.5 (0.5)	-13.4 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments	Change from Baseline to Week 9
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -5.2 to -2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

8. Secondary Outcome

Title	Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 6
Description	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.
Time Frame	Baseline (Day 1) to Week 6

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [lesion count]	-8.0 (0.5)	-11.7 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments	Change from Baseline to Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -5.0 to -2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

9. Secondary Outcome

Title	Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 3
Description	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.
Time Frame	Baseline (Day 1) to Week 3

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Placebo	Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Measure Participants	515	519
Least Squares Mean (Standard Error) [lesion count]	-5.5 (0.5)	-8.4 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sarecycline
	Comments	Change from Baseline to Week 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Analyses were based on ANCOVA model for the endpoint with treatment group and pooled study center as factors and baseline value as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -4.1 to -1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	sarecycline - placebo

Adverse Events

Time Frame	Up to 157 Days
Adverse Event Reporting Description	The number of participants at risk for Serious Adverse Events and Adverse Events was based on the Safety Population that included all participants who received at least 1 dose of study treatment.
Arm/Group Title	Placebo		Sarecycline
Arm/Group Description	Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.		Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
All Cause Mortality
	Placebo		Sarecycline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/513 (0%)		0/513 (0%)
Serious Adverse Events
	Placebo		Sarecycline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/513 (0.2%)		4/513 (0.8%)
Gastrointestinal disorders
Crohn's disease	0/513 (0%)		1/513 (0.2%)
Infections and infestations
Tonsillitis	0/513 (0%)		1/513 (0.2%)
Pregnancy, puerperium and perinatal conditions
Abortion	0/513 (0%)		1/513 (0.2%)
Psychiatric disorders
Depression	0/513 (0%)		1/513 (0.2%)
Oppositional defiant disorder	1/513 (0.2%)		0/513 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Sarecycline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/513 (0%)		0/513 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.