An Open-label, Phase IV Study Evaluating Lidose-isotretinoin Administered without Food in Patients with Severe Recalcitrant Nodular Acne: Low Relapse Rates Observed Over the 104-week Post-treatment Period

Abstract

Objective: We sought to evaluate long-term relapse rates following lidose-isotretinoin taken without food in patients with severe recalcitrant acne. Design: In this single-arm, open-label study, 197 patients received twice-daily lidose-isotretinoin without food for up to 20 weeks. Patients with a 75-percent or higher adherence rate with the protocol-designated dosage and end-of-treatment lesion counts were predefined as the per-protocol (PP) population and evaluated in a 104-week post-treatment period (PTP) to determine the proportion of patients requiring retreatment. Setting: Participants were enrolled from 21 sites across the United States. Participants: Eligible participants were male or nonpregnant, nonlactating female, aged between 12 to 45 years, weighing 40 to 110 kg, and with no prior exposure to systemic isotretinoin or systemic retinoids. Acne was considered severe enough for treatment if the patient had five or more facial nodule lesions. Measurements: Patients were observed to determine whether they required retreatment with isotretinoin or any acne therapy during the PTP. Lesion counts and assessments of acne severity, quality of life, and adverse events were completed. Results: Of the 166 patients in the PP population, seven (4.2%; 95% confidence interval [CI]: 1.7%-8.5%) were retreated with isotretinoin, 25 (15.1%; 95% CI: 10.0%-21.4%) were treated with topical and/or oral nonisotretinoin therapies including over-the-counter therapies or intralesional injections, and 137 (82.5%; 95% CI: 75.8%-88.0%) required no retreatment. Isotretinoin retreatment was most common in male patients aged 14 to 18 years. Conclusion: Long-term relapse rates for lidose-isotretinoin taken without food for 20 weeks were at the low end of those published for traditional isotretinoin taken with a high-fat/high-calorie meal. ClinicalTrials.gov Registration: NCT02457520.

Keywords: Acne; isotretinoin; lidose-isotretinoin; relapse; retreatment.

Conflict of interest statement

FUNDING:The study was funded by Sun Pharmaceutical Industries, Inc. DISCLOSURES:Dr. Del Rosso has received grants from and/or served as a consultant/advisor, investigator, and/or speaker for Abbvie, Aclaris, Almirall, Athenex, BioPharmX, Botanix, Cassiopeia, Celgene, Cutanea (Biofrontera), Dermira, Encore, EPI Health, Ferndale, Foamix, Galderma, Genentech, LaRoche Posay, Leo Pharma, Menlo Therapeutics, Novan, Ortho Dermatologics, Pfizer, Promius, Regeneron, Sanofi/Genzyme, Sonoma (Intraderm), Sol Gel, Sun Pharmaceuticals, and Verrica. Dr. Stein Gold has received grants from and/or served as a consultant, investigator and/or a speaker for Foamix, Galderma, Novartis, Ortho Dermatologies, Sol Gel, and Sun Pharmaceuticals. Dr. Segal is an employee of Sun Pharmaceutical Industries, Inc. Dr. Zaenglein has received grants from and/or served as a consultant/advisor and/or investigator for Abbvie, Allergan, Incyte, Innovaderm, Ortho Dermatologics, Pfizer, and Ranbaxy/Sun Pharmaceuticals.

Copyright © 2019. Matrix Medical Communications. All rights reserved.

Figures

FIGURE 1.

Patient disposition— aThe 4 patients who did not start treatment are included in the breakdown of the patients who discontinued from the ATP. bOne patient discontinued treatment because of an AE on Day 112; the patient was observed until AE resolution on Day 191. cThree discontiunued because of pharmacy access issues, and one because of a move away from the study site. dCompleted PTP describes completion of the 104-week period of follow-up visits. AE: adverse event; ATP: active treatment period; ITT: intention-to-treat; PP: per-protocol; PTP: post-treatment period

FIGURE 2.

Rates of retreatment in the PTP by type of medication—The length of the error bar is half the length of the exact 95% confidence interval for the percentage shown. Patients could be included in more than one retreatment column if they had received more than one retreatment type in the PTP. aSubgroup of patients receiving prescription acne medication; OTC: over-the-counter; PTP: post-treatment period

FIGURE 3.

Rates of retreatment in the PTP by age and sex—The length of the error bar is half the length of the exact 95% confidence interval for the percentage shown. Patients could be included in more than one retreatment group if they had received more than one retreatment type in the PTP. aOther acne medication included all over-the-counter medications, intralesional injections, and topical and oral prescription medications except oral retinoids. PTP: post-treatment period