Trial Outcomes & Findings for Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne (NCT NCT02322866)

NCT ID: NCT02322866

Last Updated: 2019-02-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1034 participants
• Primary outcome timeframe: Baseline (Day 1) to Week 12
• Results posted on: 2019-02-01

Participant Flow

Participant milestones

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

Reasons for withdrawal

Measure	Placebo Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline Sarecycline tablets, 1.5 milligram(mg)/kilogram(kg)/day, taken orally once daily for 12 weeks.
Overall Study Adverse Event	6	11
Overall Study Withdrawal of Consent	16	25
Overall Study Lost to Follow-up	36	39
Overall Study Protocol Violation	1	0
Overall Study Noncompliance with Treatment	3	4
Overall Study Lack of Efficacy	3	1
Overall Study Other Miscellaneous Reasons	6	6

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.	Total n=1034 Participants Total of all reporting groups
Age, Customized ≥9 and <12 years	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Age, Customized ≥12 and <18 years	256 participants n=5 Participants	227 participants n=7 Participants	483 participants n=5 Participants
Age, Customized ≥18 years	255 participants n=5 Participants	285 participants n=7 Participants	540 participants n=5 Participants
Sex: Female, Male Female	292 Participants n=5 Participants	315 Participants n=7 Participants	607 Participants n=5 Participants
Sex: Female, Male Male	223 Participants n=5 Participants	204 Participants n=7 Participants	427 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 12

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 12	-10.7 lesion count Standard Error 0.5	-15.1 lesion count Standard Error 0.6

PRIMARY outcome

Timeframe: Week 12

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Percentage of Participants With Investigator's Global Assessment (IGA) Scale Success at Week 12	15.3 percentage of participants	22.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 12	-35.4 percent change in lesion counts Standard Error 1.8	-49.9 percent change in lesion counts Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 9

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 9	-31.9 percent change in lesion counts Standard Error 1.7	-44.5 percent change in lesion counts Standard Error 1.7

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 6

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 6	-27.3 percent change in lesion counts Standard Error 1.6	-39.1 percent change in lesion counts Standard Error 1.6

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 3

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 3	-18.6 percent change in lesion counts Standard Error 1.6	-28.0 percent change in lesion counts Standard Error 1.5

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 9

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 9	-9.5 lesion count Standard Error 0.5	-13.4 lesion count Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 6

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 6	-8.0 lesion count Standard Error 0.5	-11.7 lesion count Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 3

Population: ITT Population included all randomized participants.

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.

Outcome measures

Measure	Placebo n=515 Participants Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=519 Participants Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 3	-5.5 lesion count Standard Error 0.5	-8.4 lesion count Standard Error 0.5

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Sarecycline

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=513 participants at risk Placebo-matching sarecycline tablets, taken orally once daily for 12 weeks.	Sarecycline n=513 participants at risk Sarecycline tablets, 1.5 mg/kg/day, taken orally once daily for 12 weeks.
Gastrointestinal disorders Crohn's disease	0.00% 0/513 • Up to 157 Days 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.	0.19% 1/513 • Up to 157 Days 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.
Infections and infestations Tonsillitis	0.00% 0/513 • Up to 157 Days 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.	0.19% 1/513 • Up to 157 Days 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.
Pregnancy, puerperium and perinatal conditions Abortion	0.00% 0/513 • Up to 157 Days 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.	0.19% 1/513 • Up to 157 Days 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.
Psychiatric disorders Depression	0.00% 0/513 • Up to 157 Days 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.	0.19% 1/513 • Up to 157 Days 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.
Psychiatric disorders Oppositional defiant disorder	0.19% 1/513 • Up to 157 Days 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.	0.00% 0/513 • Up to 157 Days 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.

Other adverse events

Adverse event data not reported

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: clinicaltrials@allergan.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER