A Safety and Efficacy Study of Dapsone Gel in Patients With Acne Vulgaris

• ClinicalTrials.gov Identifier: NCT01974141
• Recruitment Status: Completed
• First Posted: November 1, 2013
• Results First Posted: February 6, 2017
• Last Update Posted: October 8, 2018
• Sponsor: Almirall, S.A.
• Collaborator: Allergan
• Information provided by (Responsible Party): Almirall, S.A.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Acne Vulgaris
• Interventions: Drug: Dapsone Gel; Drug: Dapsone Gel Vehicle
• Enrollment: 2102

Participant Flow

Recruitment Details
Pre-assignment Details	The Intent-to-Treat population is reflected in the overall study properties. This population excludes patients from a site with Good Clinical Practice violations. All data from this site are excluded in the study results.

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Period Title: Overall Study
Started	1044	1058
Completed	948	976
Not Completed	96	82
Reason Not Completed
Other Reasons	28	18
Protocol Violation	2	6
Personal Reasons	21	20
Lost to Follow-up	38	29
Pregnancy	3	3
Lack of Efficacy	0	1
Adverse Event	4	5

Baseline Characteristics

Arm/Group Title		Dapsone Gel	Dapsone Gel Vehicle	Total
Arm/Group Description		Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		1044	1058	2102
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1044 participants	1058 participants	2102 participants
		20.0 (7.41)	20.0 (7.53)	20.0 (7.47)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1044 participants	1058 participants	2102 participants
	Female	591 56.6%	582 55.0%	1173 55.8%
	Male	453 43.4%	476 45.0%	929 44.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With a Score of 0 (None) or 1 (Minimal) on the 5-point Global Acne Assessment Score (GAAS)
Description	The Investigator evaluated the patient's acne severity using the 5-point GAAS scale with 0 being none and 4 being severe. The complete scale is as follow: Grade 0 (none) = No evidence of facila acne vulgaris; Grade 1 (minimal) = Few noninflammatory lesions (comedones) are present, a few inflammatory lesions (papules/pustules) may be present, no nodulo-cyctic lesions are allowed; Grade 2 (mild) = Several to many noninflammatory lesions (comedones) are present, a few inflammatory lesions (papules/pustules) are present, no nodulo-cystic lesions are allowed; Grade 3 (moderate) = Many noninflammatory (comedones) and inflammatory lesions (papules/pustules) are present, no nodulo-cystic lesions are allowed; Grade 4 (severe) = Significant degree of inflammatory disease, papules/pustules are a predominant feature, a few nodulo-cystic lesions may be present, comedones may be present.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Measure Type: Number; Unit of Measure: Percentage of Patients
	29.9	21.2

2. Primary Outcome

Title	Change From Baseline in Inflammatory Facial Lesion Counts
Description	The Investigator evaluated the patient's inflammatory lesions (papule, pustule and nodule/cyst). A negative change from baseline indicates a reduction in lesion counts (improvement) and a positive change from baseline indicates an increase in lesion counts (worsening).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Mean (Standard Error); Unit of Measure: Number of Inflammatory Lesions
Baseline	29.0 (0.25)	29.4 (0.25)
Change from Baseline at Week 12	-16.1 (0.32)	-14.1 (0.32)

3. Primary Outcome

Title	Change From Baseline in Noninflammatory Facial Lesion Counts
Description	The Investigator evaluated the patient's noninflammatory lesions (papule, pustule and nodule/cyst). A negative change from baseline indicates a reduction in lesion counts (improvement) and a positive change from baseline indicates an increase in lesion counts (worsening).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Mean (Standard Error); Unit of Measure: Number of Noninflammatory Lesions
Baseline	47.0 (0.53)	48.7 (0.53)
Change from Baseline at Week 12	-20.8 (0.56)	-17.6 (0.55)

4. Secondary Outcome

Title	Change From Baseline in Total Lesion Counts
Description	The Investigator evaluated the patient's inflammatory (papule, pustule and nodule/cyst) and non-inflammatory (blackhead and whitehead) lesions. A papule is a small, red, solid elevation less than 1.0 cm in diameter, a pustule is a small, circumscribed elevation of the skin that contains yellow-white exudate and a nodule/cyst is a circumscribed, elevated, solid lesion generally more than 0.5 cm in diameter with palpable depth. The total lesion count was the sum of the inflammatory and non-inflammatory lesion counts. A negative change from baseline indicates a reduction in lesion counts (improvement) and a positive change from baseline indicates an increase in lesion counts (worsening).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Least Squares Mean (Standard Error); Unit of Measure: Total Lesion Counts
Baseline	75.9 (0.65)	78.1 (0.65)
Change from Baseline at Week 12	-36.9 (0.76)	-31.7 (0.75)

5. Secondary Outcome

Title	Percentage Change From Baseline in Total Lesion Counts
Description	The Investigator evaluated the patient's Inflammatory (papule, pustule and nodule/cyst) and Non-inflammatory (blackhead and whitehead) lesions. A papule is a small, red, solid elevation less than 1.0 cm in diameter, a pustule is a small, circumscribed elevation of the skin that contains yellow-white exudate and a nodule/cyst is a circumscribed, elevated, solid lesion generally more than 0.5 cm in diameter with palpable depth. The total lesion count was the sum of the inflammatory and non-inflammatory lesion counts. A negative percent change from baseline indicates a reduction in lesion counts (improvement) and a positive percent change from baseline indicates an increase in lesion counts (worsening).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Least Squares Mean (Standard Error); Unit of Measure: Percent Change in Lesion Count
	-48.7 (0.95)	-42.4 (0.93)

6. Secondary Outcome

Title	Percentage of Patients Reporting "Very Good" or "Excellent" on Item 10 of the 5-Point Acne Symptom Impact Scale (ASIS)
Description	The patient assessed the impact of their acne vulgaris on the look of their face using item 10 on the 5-point ASIS. Item 10 scores range from 1 (Excellent) to 5 (Bad). The percentage of patients who had an ASIS score of 4 (Fair) or 5 (Bad) at baseline and who reported “Very good” or “Excellent” at Week 12 are reported.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients with data at this time point, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	910	913
Measure Type: Number; Unit of Measure: Percentage of Patients
	23.8	19.2

7. Secondary Outcome

Title	Change From Baseline in the 9-Item ASIS Sign Domain Score
Description	The patient assessed signs of acne vulgaris using the ASIS. The sign domain is a composite of 9 items of the 17 items on the overall scale. Each of the items is assessed on a 5-point scale: 0 (best) to 4 (worst). The sign domain score is calculated as the average of the 9 items for a total possible score of 0 to 4. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
Baseline	4.2 (0.69)	4.2 (0.71)
Change from Baseline at Week 12	-0.73 (0.677)	-0.69 (0.678)

8. Secondary Outcome

Title	Percentage of Patients Reporting at Least a 1-Grade Improvement From Baseline in Facial Oiliness on a the 5-Point ASIS Scale
Description	The patient assessed their facial oiliness using item 1 on the 5-point ASIS. Item 1 scores ranged from 0 (Not at all oily) to 4 (Very oily). The percentage of patients who reported at least a 1-grade improvement from baseline in their facial oiliness are reported.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Measure Type: Number; Unit of Measure: Percentage of Patients
	45.7	51.8

9. Secondary Outcome

Title	Percentage of Patients Reporting at Least a 1-Grade Improvement From Baseline in Facial Redness on a the 5-Point ASIS Scale
Description	The patient assessed their facial redness using item 8 on the 5-point ASIS. Item 8 scores ranged from 0 (Not at all red) to 4 (Very red). The percentage of patients who reported at least a 1-grade improvement from baseline in their facial redness are reported.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients, excluding patients from a site with Good Clinical Practice violations

Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description:	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
Overall Number of Participants Analyzed	1044	1058
Measure Type: Number; Unit of Measure: Percentage of Patients
	55.6	53.0

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	The Safety Population was used to assess adverse events and serious adverse events. The Safety Population included all patients who applied study treatment at least once, excluding patients from a site with Good Clinical Practice violations.
Arm/Group Title	Dapsone Gel	Dapsone Gel Vehicle
Arm/Group Description	Dapsone gel applied topically to the face and to affected areas of the trunk once daily for 12 weeks.	Dapsone gel vehicle applied topically to the face and to affected areas of the trunk once daily for 12 weeks.
All-Cause Mortality
	Dapsone Gel	Dapsone Gel Vehicle
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Dapsone Gel	Dapsone Gel Vehicle
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/1044 (0.29%)	5/1057 (0.47%)
General disorders
Application Site Dermatitis * 1	1/1044 (0.10%)	0/1057 (0.00%)
Infections and infestations
Appendicitis † 1	1/1044 (0.10%)	0/1057 (0.00%)
Injury, poisoning and procedural complications
Tibia Fracture † 1	1/1044 (0.10%)	0/1057 (0.00%)
Lumbar Vertebral Fracture † 1	0/1044 (0.00%)	1/1057 (0.09%)
Psychiatric disorders
Affective Disorder † 1	0/1044 (0.00%)	1/1057 (0.09%)
Depression † 1	0/1044 (0.00%)	1/1057 (0.09%)
Anxiety * 1	0/1044 (0.00%)	1/1057 (0.09%)
Surgical and medical procedures
Abortion Induced † 1 [1]	0/591 (0.00%)	1/581 (0.17%)
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA version 17.0; [1] FEMALES ONLY
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Dapsone Gel	Dapsone Gel Vehicle
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/1044 (0.00%)	0/1057 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

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.

Results Point of Contact

• Name/Title: Therapeutic Area Head,
• Organization: Allergan, Inc
• Phone: 714-246-4500
• EMail: clinicaltrials@allergan.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tanghetti E, Harper J, Baldwin H, Kircik L, Bai Z, Alvandi N. Once-Daily Topical Dapsone Gel, 7.5%: Effective for Acne Vulgaris Regardless of Baseline Lesion Count, With Superior Efficacy in Females. J Drugs Dermatol. 2018 Nov 1;17(11):1192-1198.

Tanghetti E, Harper J, Baldwin H, Kircik L, Bai Z, Alvandi N. Once-Daily Topical Dapsone Gel, 7.5%: Effective for Acne Vulgaris Regardless of Baseline Lesion Count, With Superior Efficacy in Females. J Drugs Dermatol. 2018 Nov 1;17(11):1192-1198.

Tanghetti E, Harper J, Baldwin H, Kircik L, Bai Z, Alvandi N. Once-Daily Topical Dapsone Gel, 7.5%: Effective for Acne Vulgaris Regardless of Baseline Lesion Count, With Superior Efficacy in Females. J Drugs Dermatol. 2018 Nov 1;17(11):1192-1198.

Thiboutot DM, Kircik L, McMichael A, Cook-Bolden FE, Tyring SK, Berk DR, Chang-Lin JE, Lin V, Kaoukhov A. Efficacy, Safety, and Dermal Tolerability of Dapsone Gel, 7.5% in Patients with Moderate Acne Vulgaris: A Pooled Analysis of Two Phase 3 Trials. J Clin Aesthet Dermatol. 2016 Oct;9(10):18-27. Epub 2016 Oct 1.

• Responsible Party: Almirall, S.A.
• ClinicalTrials.gov Identifier: NCT01974141 History of Changes
• Other Study ID Numbers: 225678-006
• First Submitted: October 28, 2013
• First Posted: November 1, 2013
• Results First Submitted: April 7, 2016
• Results First Posted: February 6, 2017
• Last Update Posted: October 8, 2018