Safety and Pharmacokinetics of Once-Daily Dapsone Gel, 7.5% in Patients With Moderate Acne Vulgaris.
J Drugs Dermatol
; 15(10): 1250-1259, 2016 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-27741344
ABSTRACT
BACKGROUND:
Reducing the dosing frequency of topical acne treatments to once daily may improve adherence.OBJECTIVE:
Evaluate pharmacokinetics (PK), safety, and tolerability of 3 formulations of once-daily dapsone gel, 7.5% and of twice-daily dapsone gel, 5% over 28 days in patients with moderate acne vulgaris.METHODS:
This phase 1, multicenter, parallel-group study randomized males and females aged 16 to 35 years to 1 of 3 dapsone gel, 7.5% formulations (DAP-11078, DAP-11079, or DAP-11080 double-blind; applied once daily) or to dapsone gel, 5% (investigator-blinded only, applied twice-daily). Blood samples were collected for PK assessments of dapsone and its metabolites, N-acetyl dapsone (NAD) and dapsone hydroxylamine (DHA), before the morning dose on days 1, 7, 14, 18, 21, 26, 27, and 28, and at several follow-up time points (days 29-32). Safety profile assessments included adverse events (AEs), physical examinations, laboratory tests, and local tolerability assessments.RESULTS:
Steady-state dapsone, NAD, and DHA concentrations were reached within 7 days of the first dose in all treatment groups. Daily systemic exposures of the 3 dapsone gel, 7.5% formulations were approximately 25% to 40% lower than that for dapsone gel, 5%, and these differences were statistically significant. Among the 3 dapsone gel, 7.5% formulations, the highest daily exposure of dapsone (per the AUC) was observed with DAP-11080, with respective Cmax and AUC0-24 being approximately 28.6% and 28.7% lower relative to dapsone gel, 5%. Most AEs were mild to moderate in intensity. The safety profiles for all 3 formulations of once-daily dapsone, 7.5% gel and twice-daily dapsone gel, 5% were similar following 28 days of topical administration. All 4 dapsone formulations were well tolerated.CONCLUSIONS:
This study demonstrated lower systemic exposure with all 3 once-daily dapsone gel, 7.5% formulations than with twice-daily dapsone gel, 5%. All 4 formulations were well tolerated and demonstrated similar safety profiles.J Drugs Dermatol. 2016;15(10)1250-1259.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acne Vulgaris
/
Dapsone
/
Anti-Infective Agents
Type of study:
Clinical_trials
/
Diagnostic_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Drugs Dermatol
Journal subject:
DERMATOLOGIA
Year:
2016
Document type:
Article