Trial Outcomes & Findings for Safety and Efficacy Trial of ACZONE (Dapsone) Gel, 7.5% in 9 to 11 Year-Old Patients With Acne Vulgaris (NCT NCT02959970)

Results Overview

An AE was defined as "any untoward medical occurrence in a clinical trial participant (regardless of the administration of the study drug and its causal relationship to it). An AE could therefore, be any unfavorable and unintended medical occurrence during the participant's participation in the trial, including deterioration of a pre-existing medical condition, an abnormal clinically significant finding in a laboratory assessment, or an abnormal clinically significant finding in the physical examination or vital sign.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

100 participants

Primary outcome timeframe

From Baseline (Day 1) until Week 12

Results posted on

2020-03-03

Participant Flow

The study was conducted at 20 sites in United States (US) between 31 October 2016 (first participant first visit) and 09 March 2018 (last participant last visit).

A total of 105 participants were screened, out of which 100 participants were enrolled into either of the 2 cohorts, Pharmacokinetic (PK) Cohort and Non-PK Cohort.

Participant milestones

Participant milestones
Measure	PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Overall Study STARTED	17	83
Overall Study COMPLETED	15	76
Overall Study NOT COMPLETED	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	0	2
Overall Study Lost to Follow-up	1	5

Baseline Characteristics

Safety and Efficacy Trial of ACZONE (Dapsone) Gel, 7.5% in 9 to 11 Year-Old Patients With Acne Vulgaris

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.	Total n=100 Participants Total of all reporting groups
Age, Continuous	10.1 years STANDARD_DEVIATION 0.9 • n=5 Participants	10.4 years STANDARD_DEVIATION 0.7 • n=7 Participants	10.4 years STANDARD_DEVIATION 0.8 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	59 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	24 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	23 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	60 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	19 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	53 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline (Day 1) until Week 12

Population: Safety population included all participants who received at least one application of study drug.

An AE was defined as "any untoward medical occurrence in a clinical trial participant (regardless of the administration of the study drug and its causal relationship to it). An AE could therefore, be any unfavorable and unintended medical occurrence during the participant's participation in the trial, including deterioration of a pre-existing medical condition, an abnormal clinically significant finding in a laboratory assessment, or an abnormal clinically significant finding in the physical examination or vital sign.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Number of Participants With Adverse Events (AE)	5 Participants	16 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 12

Population: Safety population included all participants who received at least one application of study drug.

Change from baseline in systolic and diastolic blood pressure was evaluated. Change from baseline was calculated by subtracting post-dose value from baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure	3.9 millimeter of mercury (mmHg) Standard Deviation 8.2	0.1 millimeter of mercury (mmHg) Standard Deviation 10.1
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure	2.3 millimeter of mercury (mmHg) Standard Deviation 5.9	0.4 millimeter of mercury (mmHg) Standard Deviation 9.1

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 12

Population: Safety population included all participants who received at least one application of study drug.

Change from baseline in heart rate was evaluated. Change from baseline was calculated by subtracting post-dose value from baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Change From Baseline in Heart Rate	-0.8 beats per minute (beats/min) Standard Deviation 14.0	0.6 beats per minute (beats/min) Standard Deviation 9.5

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 12

Population: Safety population included all participants who received at least one application of study drug.

Change from baseline in respiratory rate was assessed. Change from baseline was calculated by subtracting post-dose value from baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Change From Baseline in Respiratory Rate	0.5 breaths per minute (breaths/min) Standard Deviation 2.4	-0.1 breaths per minute (breaths/min) Standard Deviation 1.6

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 12

Population: Safety population included all participants who received at least one application of study drug.

Change from baseline in body temperature was assessed. Change from baseline was calculated by subtracting post-dose value from baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Change From Baseline in Body Temperature	0.08 degree celsius (°C) Standard Deviation 0.26	0.10 degree celsius (°C) Standard Deviation 0.38

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 12

Population: Safety population included all participants who received at least one application of study drug.

Change from baseline in weight was assessed. Change from baseline was calculated by subtracting post-dose value from baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Change From Baseline in Weight	0.70 kilogram (kg) Standard Deviation 1.98	1.48 kilogram (kg) Standard Deviation 1.72

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 12

Population: Safety population included all participants who received at least one application of study drug.

Change from baseline in height was assessed. Change from baseline was calculated by subtracting post-dose value from baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Change From Baseline in Height	0.21 centimeter (cm) Standard Deviation 0.76	1.01 centimeter (cm) Standard Deviation 1.77

PRIMARY outcome

Timeframe: Week 12

Population: Safety population included all participants who received at least one application of study drug. Here, "number analyzed" signifies number of participants with available data for the specified category.

Local dermal tolerability was evaluated by investigator in terms of presence and absence of dryness, scaling and erythema symptoms and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point scale of 0 - 3, where 0 = none (no dryness, scaling and erythema) and 3 = severe (marked roughness, heavy scale production and intense redness). The higher score indicated severe symptoms.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Scaling: Moderate (2)	0 participants	1 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Dryness: None (0)	15 participants	71 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Dryness: Mild (1)	0 participants	6 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Dryness: Moderate (2)	0 participants	0 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Dryness: Severe (3)	0 participants	0 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Scaling: None (0)	15 participants	70 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Scaling: Mild (1)	0 participants	6 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Scaling: Severe (3)	0 participants	0 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Erythema: None (0)	13 participants	65 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Erythema: Mild (1)	2 participants	12 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Erythema: Moderate (2)	0 participants	0 participants
Local Dermal Tolerability: Number of Participants With Dryness, Scaling and Erythema as Assessed by Investigator Erythema: Severe (3)	0 participants	0 participants

PRIMARY outcome

Timeframe: Week 12

Population: Safety population included all participants who received at least one application of study drug. Here, "number analyzed" signifies number of participants with available data for the specified category.

Local dermal tolerability was evaluated by participants in terms of presence and absence of prickling pain sensation immediately after (within 5 minutes of dosing) and its severity in the areas of body where medication was applied (face). Stinging/burning symptoms were graded on a 4-point scale of 0 - 3 where 0 = none (no stinging/burning), 1 = mild (slight warm, tingling/stinging sensation; not really bothersome), 2 = moderate (definite warm, tingling/stinging sensation that is somewhat bothersome), 3 = severe (hot, tingling/stinging sensation that has caused definite discomfort). The higher score indicated severe symptoms.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=17 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% n=83 Participants Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Local Dermal Tolerability: Number of Participants With Stinging/Burning Symptoms as Assessed by Participants None (0)	15 participants	75 participants
Local Dermal Tolerability: Number of Participants With Stinging/Burning Symptoms as Assessed by Participants Mild (1)	0 participants	2 participants
Local Dermal Tolerability: Number of Participants With Stinging/Burning Symptoms as Assessed by Participants Moderate (2)	0 participants	0 participants
Local Dermal Tolerability: Number of Participants With Stinging/Burning Symptoms as Assessed by Participants Severe (3)	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 (Pre-dose and 10 hours post-dose)

Population: Pharmacokinetic (PK) population included all participants who received applications of study drug for at least 8 days under maximal use conditions and had evaluable blood samples for PK analysis.

The mean plasma peak (10 hours postdose) concentrations of dapsone, dapsone hydroxylamine and N-acetyl dapsone were reported.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=16 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Peak Plasma Concentration of Dapsone,Dapsone Hydroxylamine and N-acetyl Dapsone at Week 1 Dapsone	20.0 nanogram per milliter (ng/mL) Standard Deviation 12.5	—
Peak Plasma Concentration of Dapsone,Dapsone Hydroxylamine and N-acetyl Dapsone at Week 1 Dapsone hydroxylamine	1.40 nanogram per milliter (ng/mL) Standard Deviation 1.10	—
Peak Plasma Concentration of Dapsone,Dapsone Hydroxylamine and N-acetyl Dapsone at Week 1 N-acetyl dapsone	9.01 nanogram per milliter (ng/mL) Standard Deviation 7.37	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 (Pre-dose)

Population: Pharmacokinetic (PK) population included all participants who received applications of study drug for at least 8 days under maximal use conditions and had evaluable blood samples for PK analysis.

The trough plasma concentrations of Dapsone, Dapsone hydroxylamine and N-acetyl dapsone were reported.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=16 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Trough Plasma Concentration of Dapsone, Dapsone Hydroxylamine and N-acetyl Dapsone at Week 1 Dapsone	17.2 ng/mL Standard Deviation 14.0	—
Trough Plasma Concentration of Dapsone, Dapsone Hydroxylamine and N-acetyl Dapsone at Week 1 Dapsone hydroxylamine	1.05 ng/mL Standard Deviation 0.979	—
Trough Plasma Concentration of Dapsone, Dapsone Hydroxylamine and N-acetyl Dapsone at Week 1 N-acetyl dapsone	7.02 ng/mL Standard Deviation 5.28	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1), Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment. This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Inflammatory lesion counts were the sum of counts of the following lesion types (face only): Papule - a small, red, solid elevation less than (\<) 1.0 centimeter (cm) in diameter; Pustule - a small, circumscribed elevation of the skin that contains yellow-white exudate; Nodule - a circumscribed, elevated, solid lesion generally more than 1.0 cm in diameter with palpable depth; Cyst - a smooth, dome-shaped, elevated, freely moveable, skin-colored, round to ovoid lesion greater than 0.7 cm in diameter. Change from baseline was calculated by subtracting post-dose value from baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Absolute Change From Baseline in Inflammatory Lesion Counts	-6.2 lesions Standard Deviation 9.3	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1), Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment.This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Inflammatory lesion counts were the sum of counts of the following lesion types (face only): Papule - a small, red, solid elevation less than 1.0 cm in diameter; Pustule - a small, circumscribed elevation of the skin that contains yellow-white exudate; Nodule - a circumscribed, elevated, solid lesion generally more than 1.0 cm in diameter with palpable depth; Cyst - a smooth, dome-shaped, elevated, freely moveable, skin colored, round to ovoid lesion greater than 0.7 cm in diameter.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Percent Change From Baseline in Inflammatory Lesion Counts	-56.38 percent change Standard Deviation 43.43	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1), Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment. This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Non-inflammatory lesion counts were defined as the sum of counts of the following lesion type (face only): open comedone - a pigmented dilated pilosebaceous orifice (blackhead); closed comedone - a tiny white papule (whitehead). Change from baseline was be calculated by subtracting post-dose value from the baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Absolute Change From Baseline in Non-inflammatory Lesion Counts	-17.8 lesions Standard Deviation 17.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1), Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment. This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Noninflammatory lesion counts were defined as the sum of counts of the following lesion type (face only): open comedone - a pigmented dilated pilosebaceous orifice (blackhead); closed comedone - a tiny white papule (whitehead).

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Percent Change From Baseline in Non-inflammatory Lesion Counts	-46.45 percent change Standard Deviation 69.90	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1), Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment.This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Total lesion counts were defined as the sum of inflammatory lesion counts and noninflammatory lesion counts (face only). Change from baseline was be calculated by subtracting post-dose value from the baseline value.

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Absolute Change From Baseline in Total Lesion Counts on Face	-24.0 lesions Standard Deviation 23.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1), Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment. This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Total lesion counts were defined as the sum of inflammatory lesion counts and noninflammatory lesion counts (face only).

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Percent Change From Baseline in Total Lesion Counts on Face	-51.91 percent change Standard Deviation 33.53	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment. This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Overall severity of acne vulgaris was evaluated by using a 5-point IGA scale: Clear (0) - (no comedones; papules or pustules, residual hyperpigmentation and erythema may be present); Almost clear (1) - (rare comedones; no more than a few small papules and pustules); Mild (2) - (easily recognizable comedones in limited numbers; +/- presence of small papules and pustules); Moderate (3) - (many comedones; +/- easily recognizable small and medium-sized papules; no nodules or cysts; Severe (4) - (widespread and numerous comedones; many small, medium-sized and large papules and pustules; nodules or cysts may or may not be present).

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Percentage of Participants With None (0) or Minimal (1) Score on the Investigator's Global Assessment (IGA) for Face	46.7 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 12

Population: Modified intent-to-treat (mITT) population included all enrolled participants who had a baseline assessment and at least one post-baseline assessment.This population was presented as combined data from both cohorts (PK Cohort: ACZONE 7.5% and Non-PK Cohort: ACZONE 7.5%).

Overall severity of acne vulgaris was evaluated by using a 5-point IGA scale: Clear (0) - (no comedones; papules or pustules, residual hyperpigmentation and erythema may be present); Almost clear (1) - (rare comedones; no more than a few small papules and pustules); Mild (2) - (easily recognizable comedones in limited numbers; +/- presence of small papules and pustules); Moderate (3) - (many comedones; +/- easily recognizable small and medium-sized papules; no nodules or cysts; Severe (4) - (widespread and numerous comedones; many small, medium-sized and large papules and pustules; nodules or cysts may or may not be present).

Outcome measures

Outcome measures
Measure	PK Cohort: ACZONE 7.5% n=98 Participants Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort: ACZONE 7.5% Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Percentage of Participants With None (0) or Minimal (1) Score Plus at Least a 2-Grade Improvement on the Investigator's Global Assessment (IGA) for Face	19.6 percentage of participants	—

Adverse Events

PK Cohort

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Non-PK Cohort

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Ayman Grada

Almirall LLC

Phone: 610-840-7107

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Authorship and manuscript composition will reflect joint cooperation between multiple investigators and sites and the Sponsor's personnel. Authorship will be established prior to the writing of the manuscript. As this study involves multiple centers, no individual publications will be allowed prior to completion of the final report of the multicenter study except as agreed with the Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	PK Cohort n=17 participants at risk Participants applied ACZONE 7.5 % gel topically, once-daily to the entire face, neck, upper chest, upper back and shoulders starting from Day 1 under maximal use conditions (2 grams per day) for Day 8 consecutive days, followed by a thin layer to their face and acne-affected areas on the upper chest, upper back, and shoulders for next 11 weeks.	Non-PK Cohort n=83 participants at risk Participants applied ACZONE 7.5% gel topically, once-daily in a thin layer to their face and acne-affected areas on upper chest, upper back, and shoulders for 12 weeks.
Gastrointestinal disorders Vomiting	5.9% 1/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	0.00% 0/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
General disorders Pyrexia	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Immune system disorders Seasonal allergy	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Infections and infestations Upper respiratory tract infection	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	3.6% 3/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Infections and infestations Nasopharyngitis	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	2.4% 2/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Infections and infestations Pharyngitis streptococcal	5.9% 1/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Infections and infestations Gastroenteritis	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Infections and infestations Impetigo	5.9% 1/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	0.00% 0/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Infections and infestations Molluscum contagiosum	5.9% 1/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	0.00% 0/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Injury, poisoning and procedural complications Sunburn	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Investigations Blood iron decreased	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Investigations Vitamin D decreased	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Nervous system disorders Dizziness	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Nervous system disorders Headache	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Psychiatric disorders Insomnia	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Skin and subcutaneous tissue disorders Dermatitis contact	5.9% 1/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	2.4% 2/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Skin and subcutaneous tissue disorders Pruritis	0.00% 0/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	1.2% 1/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.
Skin and subcutaneous tissue disorders Skin pigmentation	5.9% 1/17 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.	0.00% 0/83 • From baseline (Day 1) until Week 12 Reported AEs were treatment-emergent AEs that developed/worsened during the 'on-treatment period' (defined as the period from the time of the first dose of the drug until 12 weeks). The analysis was performed on the safety population.