Safety and Efficacy of ACU-D1 in the Treatment of Acne Rosacea

• Sponsor: Accuitis, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03064438
• Collaborator: (none)
• Enrollment: 40
• Locations: 2
• Arms: 2
• Actual Duration (Months): 6.6
• Patients Per Site: 20
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

The study evaluated the safety, tolerability, and efficacy of ACCU-D1 when applied twice daily for 12 weeks in adult participants with moderate to severe acne rosacea. Two-third of the participants received ACCU-D1 while one-third of the participants received vehicle control.

Condition or Disease	Intervention/Treatment	Phase
Acne Rosacea	Drug: ACCU-D1; Drug: Vehicle	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A RANDOMIZED, DOUBLE-BLIND, VEHICLE CONTROLLED, PROOF-OF CONCEPT STUDY OF THE SAFETY AND EFFICACY OF ACU-D1 OINTMENT IN SUBJECTS WITH ACNE ROSACEA
• Actual Study Start Date: Nov 28, 2017
• Actual Primary Completion Date: Jun 5, 2018
• Actual Study Completion Date: Jun 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ACU-D1 Ointment Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Drug: ACCU-D1; ACCU-D1
Placebo Comparator: ACU-D1 Ointment Vehicle Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.	Drug: Vehicle; Placebo Comparator

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Total Lesion Count at Week 12 [Baseline, Week 12]

   Total lesion count was the sum of counts of the following lesion types (face only): Papule - raised inflammatory lesions, <0.5 cm in diameter with no visible purulent material; Pustule - raised inflammatory lesions, <0.5 cm in diameter with visible purulent material; Nodule - any circumscribed, inflammatory mass ≥0.5 cm in diameter.

Secondary Outcome Measures

1. Percent Change From Baseline in Investigator's Global Assessment (IGA) Score at Weeks 2, 4, 8, and 12 [Baseline; Weeks 2, 4, 8, and 12]

   The IGA score is an ordered categorical value ranging from 0 (clear) to 4 (severe). A lower score indicated improvement in the condition. Score 0 (clear): no papules or pustules, no nodules, none or barely perceptible erythema Score 1 (near clear): very few (≤3) papules and/or pustules, no nodules, very mild erythema Score 2 (mild): few papules and pustules present, no nodules, mild erythema Score 3 (moderate): several papules and pustules are the predominant features, ≤2 nodules may be present, moderate erythema Score 4 (severe): numerous papules and pustules, multiple nodules may be present, severe erythema

2. Percentage of Participants Who Were Treatment Responders at Week 12 [Baseline, Week 12]

   Treatment responders were defined as participants who have either (1) 2 ordinal or more reductions in the IGA score from baseline or (2) an IGA score of 0 or 1. The IGA score is an ordered categorical value ranging from 0 (clear) to 4 (severe). A lower score indicated improvement in the condition. Score 0 (clear): no papules or pustules, no nodules, none or barely perceptible erythema Score 1 (near clear): very few (≤3) papules and/or pustules, no nodules, very mild erythema Score 2 (mild): few papules and pustules present, no nodules, mild erythema Score 3 (moderate): several papules and pustules are the predominant features, ≤2 nodules may be present, moderate erythema Score 4 (severe): numerous papules and pustules, multiple nodules may be present, severe erythema

3. Change From Baseline in Papule Lesions at Weeks 2, 4, 8, and 12 [Baseline; Weeks 2, 4, 8, and 12]

   Papule - raised inflammatory lesions, <0.5 cm in diameter with no visible purulent material

4. Change From Baseline in Pustule Lesions at Weeks 2, 4, 8, and 12 [Baseline; Weeks 2, 4, 8, and 12]

   Pustule - raised inflammatory lesions, <0.5 cm in diameter with visible purulent material

5. Change From Baseline in Nodule Lesions at Weeks 2, 4, 8, and 12 [Baseline; Weeks 2, 4, 8, and 12]

   Nodule - any circumscribed, inflammatory mass ≥0.5 cm in diameter

6. Change From Baseline in Papules + Pustules Lesions at Weeks 2, 4, 8, and 12 [Baseline; Weeks 2, 4, 8, and 12]

   Papules + pustules lesions were the sum of counts of papule (raised inflammatory lesions, <0.5 cm in diameter with no visible purulent material) and pustule (raised inflammatory lesions, <0.5 cm in diameter with visible purulent material) lesions.

7. Number of Participants With Adverse Events [Baseline to Week 14]

   Number of participants reporting any adverse event including local tolerability of signs and symptoms of irritation, clinical laboratory safety tests, and vital signs.

Other Outcome Measures

1. Number of Participants With Erythema Score Based on Local Tolerability as Assessed by the Investigator at Week 12 [Week 12]

   Erythema score was evaluated by the investigator on a 0 to 3 scale with a lower score indicating lesser severity. Score 0 (clear): no erythema present Score 1 (mild): slight erythema Score 2 (moderate): definite erythema Score 3 (severe): marked, fiery erythema

2. Number of Participants With Erythema Score Based on Local Tolerability as Assessed by the Investigator at Day 1 (Post-application) and Weeks 2, 4, 8, and 14 [Day 1 (Post-application) and Weeks 2, 4, 8, and 14]

   Erythema score was evaluated by the investigator on a 0 to 3 scale with a lower score indicating lesser severity. Score 0 (clear): no erythema present Score 1 (mild): slight erythema Score 2 (moderate): definite erythema Score 3 (severe): marked, fiery erythema

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant is male or non-pregnant and non-lactating female at least 18 years of age

• Participant has a clinical diagnosis of stable papulopustular rosacea (type-2)

• Participant has a total of ≥10 and ≤40 inflammatory lesions (papules, pustules, and nodules) on the face

• Participant has ≤2 nodules on the face

• Participant has an investigator's global assessment (IGA) score of ≥3

• If the participant is a woman of childbearing potential, she has a negative urine pregnancy test and agrees to use an approved effective method of birth control for the duration of the study

• Participant is in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair evaluation of rosacea or which exposes the participant to an unacceptable risk by study participation

• Participant is willing and able to follow all study instructions and to attend all study visits

• Participant is able to comprehend and willing to sign an informed consent form

Exclusion Criteria:

• Participant is pregnant, nursing, or planning to become pregnant during the duration of the study

• Participant has used systemic glucocorticosteroids within 42 days prior to Visit 1 (inhaled and ocular glucocorticosteroids are permitted)

• Participant has used systemic antibiotics within 28 days prior to Visit 1

• Participant has used any topical glucocorticosteroids on the face within 28 days prior to Visit 1

• Participant has used any prescription or over-the-counter product for the treatment of acne or rosacea within 14 days prior to Visit 1

• Participant is currently using any therapy that, in the investigator's opinion, is a photosensitizer (for example, phenothiazines, amiodarone, quinine, thiazides, sulphonamides, quinolones, etc.)

• Participant currently has any skin disease (for example, psoriasis, atopic dermatitis, eczema), or condition (for example, actinic keratosis, photo-damage, sunburn, excessive hair, open wounds) that, in the investigator's opinion, might impair evaluation of rosacea or which exposes the subject to an unacceptable risk by study participation

• Participant currently has, on the face, or has had on the face, any of the following within the specified period prior to Visit 1 that, in the investigator's opinion, might impair evaluation of rosacea or which exposes the subject to an unacceptable risk by study participation:

• A cutaneous malignancy; 180 days

• Experienced a sunburn; 14 days

• Participant has facial hair, that in the investigator's opinion, might impair evaluation of rosacea or proper study medication application

• Participant has a history of sensitivity to any of the ingredients in the study medications

• Participant has participated in an investigational drug trial in which administration of an investigational study medication occurred within 30 days prior to Visit 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DS Research	Louisville	Kentucky	United States	40421
2	DermResearch	Austin	Texas	United States	78759

Sponsors and Collaborators

• Accuitis, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 5, 2017
• Statistical Analysis Plan - May 11, 2018

More Information

Publications

None provided.

• Responsible Party: Accuitis, Inc.
• ClinicalTrials.gov Identifier: NCT03064438
• Other Study ID Numbers: ACU-D1
• First Posted: Feb 27, 2017
• Last Update Posted: Aug 23, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Rosacea

Study Results

Participant Flow

Recruitment Details	The study was conducted at two sites in the United States.
Pre-assignment Detail	Eligible participants will be assigned in a random manner to 1 of the 2 study medications in a 2:1 ratio (ACU-D1 ointment: ACU-D1 ointment vehicle).

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Period Title: Overall Study
STARTED	27	13
COMPLETED	26	12
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle	Total
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.	Total of all reporting groups
Overall Participants	27	13	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.59 (11.537)	51.08 (12.473)	50.08 (11.708)
Sex: Female, Male (Count of Participants)
Female	23 85.2%	11 84.6%	34 85%
Male	4 14.8%	2 15.4%	6 15%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 18.5%	0 0%	5 12.5%
Not Hispanic or Latino	22 81.5%	13 100%	35 87.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	27 100%	13 100%	40 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Total lesion count (number of lesions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of lesions]	18.00 (9.413)	20.46 (9.777)	18.80 (9.479)
Erythema score based on local tolerability as assessed by the investigator (Count of Participants)
Score 0 (clear)	1 3.7%	1 7.7%	2 5%
Score 1 (mild)	5 18.5%	4 30.8%	9 22.5%
Score 2 (moderate)	16 59.3%	5 38.5%	21 52.5%
Score 3 (severe)	5 18.5%	3 23.1%	8 20%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Total Lesion Count at Week 12
Description	Total lesion count was the sum of counts of the following lesion types (face only): Papule - raised inflammatory lesions, <0.5 cm in diameter with no visible purulent material; Pustule - raised inflammatory lesions, <0.5 cm in diameter with visible purulent material; Nodule - any circumscribed, inflammatory mass ≥0.5 cm in diameter.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Number of participants included participants in the MITT population with available data at Week 12.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	26	11
Least Squares Mean (Standard Error) [number of lesions]	-10.2 (1.08)	-12.0 (1.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.366
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Squares (LS) Mean
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -2.162 to 5.727
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.95
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Investigator's Global Assessment (IGA) Score at Weeks 2, 4, 8, and 12
Description	The IGA score is an ordered categorical value ranging from 0 (clear) to 4 (severe). A lower score indicated improvement in the condition. Score 0 (clear): no papules or pustules, no nodules, none or barely perceptible erythema Score 1 (near clear): very few (≤3) papules and/or pustules, no nodules, very mild erythema Score 2 (mild): few papules and pustules present, no nodules, mild erythema Score 3 (moderate): several papules and pustules are the predominant features, ≤2 nodules may be present, moderate erythema Score 4 (severe): numerous papules and pustules, multiple nodules may be present, severe erythema
Time Frame	Baseline; Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

MITT population. Number of participants analyzed included participants with available data at specific timepoint.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	27	13
Week 2	-23 (0.2561)	-29 (0.1653)
Week 4	-35 (0.2387)	-26 (0.2771)
Week 8	-31 (0.2538)	-29 (0.2233)
Week 12	-31 (0.2588)	-26 (0.3583)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Percent change from baseline at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1099
	Comments
	Method	Van Elteren test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Percent change from baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1653
	Comments
	Method	Van Elteren test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Percent change from baseline at Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8437
	Comments
	Method	Van Elteren test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Percent change from baseline at Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4644
	Comments
	Method	Van Elteren test
	Comments

3. Secondary Outcome

Title	Percentage of Participants Who Were Treatment Responders at Week 12
Description	Treatment responders were defined as participants who have either (1) 2 ordinal or more reductions in the IGA score from baseline or (2) an IGA score of 0 or 1. The IGA score is an ordered categorical value ranging from 0 (clear) to 4 (severe). A lower score indicated improvement in the condition. Score 0 (clear): no papules or pustules, no nodules, none or barely perceptible erythema Score 1 (near clear): very few (≤3) papules and/or pustules, no nodules, very mild erythema Score 2 (mild): few papules and pustules present, no nodules, mild erythema Score 3 (moderate): several papules and pustules are the predominant features, ≤2 nodules may be present, moderate erythema Score 4 (severe): numerous papules and pustules, multiple nodules may be present, severe erythema
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

MITT population. Number of participants analyzed included participants with available IGA score at Week 12.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	26	11
Number [percentage of participants]	19.2 71.1%	18.2 140%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Change From Baseline in Papule Lesions at Weeks 2, 4, 8, and 12
Description	Papule - raised inflammatory lesions, <0.5 cm in diameter with no visible purulent material
Time Frame	Baseline; Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

MITT population. Number of participants analyzed included participants with available data at specified visits.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	27	13
Week 2	-6.6 (1.09)	-7.95 (1.57)
Week 4	-9.7 (0.97)	-8.22 (1.44)
Week 8	-8.1 (1.16)	-10.30 (1.71)
Week 12	-9.2 (1.01)	-10.98 (1.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.495
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -2.571 to 5.211
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.91
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.399
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -5.014 to 2.045
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.74
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.290
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -1.965 to 6.407
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.07
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -1.953 to 5.469
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.83
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Pustule Lesions at Weeks 2, 4, 8, and 12
Description	Pustule - raised inflammatory lesions, <0.5 cm in diameter with visible purulent material
Time Frame	Baseline; Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

MITT population. Number of participants analyzed included participants with available data at specified visits.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	27	13
Week 2	-0.4 (0.43)	-0.98 (0.62)
Week 4	-1.2 (0.20)	-1.63 (0.30)
Week 8	-1.1 (0.25)	-1.29 (0.38)
Week 12	-1.0 (0.31)	-1.04 (0.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.407
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.894 to 2.155
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.75
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.291
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.342 to 1.109
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.734
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.763 to 1.073
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline in pustule lesions at Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.952
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.128 to 1.197
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.57
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Nodule Lesions at Weeks 2, 4, 8, and 12
Description	Nodule - any circumscribed, inflammatory mass ≥0.5 cm in diameter
Time Frame	Baseline; Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

MITT population. Number of participants analyzed included participants with available data at specified visits.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	27	13
Week 2	0.0 (0.04)	0.02 (0.06)
Week 4	0.0 (0.04)	-0.05 (0.06)
Week 8	0.0 (0.04)	-0.05 (0.06)
Week 12	0.0 (0.04)	0.04 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.313
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.215 to 0.069
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.942
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.141 to 0.152
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline in nodule lesions at Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.284
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.067 to 0.226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.542
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.198 to 0.105
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Papules + Pustules Lesions at Weeks 2, 4, 8, and 12
Description	Papules + pustules lesions were the sum of counts of papule (raised inflammatory lesions, <0.5 cm in diameter with no visible purulent material) and pustule (raised inflammatory lesions, <0.5 cm in diameter with visible purulent material) lesions.
Time Frame	Baseline; Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

MITT population. Number of participants analyzed included participants with available data at specified visits.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	27	13
Week 2	-7.0 (1.16)	-8.97 (1.67)
Week 4	-10.9 (1.06)	-9.90 (1.57)
Week 8	-9.2 (1.19)	-11.65 (1.75)
Week 12	-10.2 (1.08)	-12.03 (1.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.333
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -2.135 to 6.139
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.04
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.591
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -4.882 to 2.822
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.90
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; -1.840 to 6.758
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.12
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ACU-D1 Ointment, ACU-D1 Ointment Vehicle
	Comments	Change from baseline at Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.356
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -2.131 to 5.779
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.95
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Number of participants reporting any adverse event including local tolerability of signs and symptoms of irritation, clinical laboratory safety tests, and vital signs.
Time Frame	Baseline to Week 14

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	27	13
Count of Participants [Participants]	11 40.7%	4 30.8%

9. Other Pre-specified Outcome

Title	Number of Participants With Erythema Score Based on Local Tolerability as Assessed by the Investigator at Week 12
Description	Erythema score was evaluated by the investigator on a 0 to 3 scale with a lower score indicating lesser severity. Score 0 (clear): no erythema present Score 1 (mild): slight erythema Score 2 (moderate): definite erythema Score 3 (severe): marked, fiery erythema
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least 1 dose of study medication. Number of participants analyzed included participants with available data at specified timepoints.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	26	11
Score 0 (clear)	1 3.7%	1 7.7%
Score 1 (mild)	14 51.9%	3 23.1%
Score 2 (moderate)	9 33.3%	6 46.2%
Score 3 (severe)	2 7.4%	1 7.7%

10. Other Pre-specified Outcome

Title	Number of Participants With Erythema Score Based on Local Tolerability as Assessed by the Investigator at Day 1 (Post-application) and Weeks 2, 4, 8, and 14
Description	Erythema score was evaluated by the investigator on a 0 to 3 scale with a lower score indicating lesser severity. Score 0 (clear): no erythema present Score 1 (mild): slight erythema Score 2 (moderate): definite erythema Score 3 (severe): marked, fiery erythema
Time Frame	Day 1 (Post-application) and Weeks 2, 4, 8, and 14

Outcome Measure Data

Analysis Population Description

Safety population. Number of participants analyzed included participants with available data at specified timepoints.

Arm/Group Title	ACU-D1 Ointment	ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.	Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
Measure Participants	27	13
Score 0 (clear)	1 3.7%	1 7.7%
Score 1 (mild)	9 33.3%	4 30.8%
Score 2 (moderate)	12 44.4%	4 30.8%
Score 3 (severe)	5 18.5%	4 30.8%
Score 0 (clear)	0 0%	0 0%
Score 1 (mild)	12 44.4%	7 53.8%
Score 2 (moderate)	12 44.4%	4 30.8%
Score 3 (severe)	3 11.1%	2 15.4%
Score 0 (clear)	0 0%	0 0%
Score 1 (mild)	13 48.1%	4 30.8%
Score 2 (moderate)	12 44.4%	7 53.8%
Score 3 (severe)	2 7.4%	1 7.7%
Score 0 (clear)	1 3.7%	1 7.7%
Score 1 (mild)	11 40.7%	5 38.5%
Score 2 (moderate)	13 48.1%	6 46.2%
Score 3 (severe)	2 7.4%	0 0%
Score 0 (clear)	2 7.4%	1 7.7%
Score 1 (mild)	8 29.6%	3 23.1%
Score 2 (moderate)	13 48.1%	5 38.5%
Score 3 (severe)	3 11.1%	3 23.1%

Adverse Events

Time Frame	Baseline up to Week 14
Adverse Event Reporting Description	Safety population
Arm/Group Title	ACU-D1 Ointment		ACU-D1 Ointment Vehicle
Arm/Group Description	Twice-daily application of ACU-D1 ointment to the face for 12 weeks.		Twice-daily application of ACU-D1 ointment vehicle to the face for 12 weeks.
All Cause Mortality
	ACU-D1 Ointment		ACU-D1 Ointment Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/13 (0%)
Serious Adverse Events
	ACU-D1 Ointment		ACU-D1 Ointment Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	ACU-D1 Ointment		ACU-D1 Ointment Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/27 (40.7%)		4/13 (30.8%)
Gastrointestinal disorders
Vomiting	1/27 (3.7%)		0/13 (0%)
General disorders
Administration site dryness	1/27 (3.7%)		1/13 (7.7%)
Administration site warmth	1/27 (3.7%)		0/13 (0%)
Application site perspiration	1/27 (3.7%)		0/13 (0%)
Infections and infestations
Ear infection	1/27 (3.7%)		0/13 (0%)
Nasopharyngitis	2/27 (7.4%)		2/13 (15.4%)
Respiratory tract infection	1/27 (3.7%)		0/13 (0%)
Sinusitis	1/27 (3.7%)		0/13 (0%)
Injury, poisoning and procedural complications
Tibia fracture	1/27 (3.7%)		0/13 (0%)
Investigations
White blood cell count decreased	0/27 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
Vitamin D deficiency	1/27 (3.7%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/27 (0%)		1/13 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.