An open-label study evaluating the quality of life, long-term efficacy, and safety of lidose-isotretinoin (ABSORICA®) capsules administered without food in patients with severe recalcitrant nodular acne: interim analysis of 20-week active treatment period
Presenters: Zaenglein A1, Del Rosso J2
Affiliations: 1Department of Dermatology, Pennsylvania State University, Hershey, PA; 2JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV
Background/Objective: Severe acne is known to have a significant adverse effect on self-esteem and quality of life (QoL). Effective treatment of acne with isotretinoin can subsequently improve the patient’s QoL. The timing of QoL improvement over the course of treatment with lidose-isotretinoin has not been established. Isotretinoin products must be taken with a high-fat meal to achieve optimal absorption. Fasted plasma levels of isotretinoin can be nearly 60-percent lower than fed levels. Nonadherence with the food intake requirements can potentially compromise the long-term efficacy of isotretinoin. Absorption of lidose-isotretinoin is less dependent on the amount and/or type of food intake, and it can be taken without meals while still providing a reliable isotretinoin blood concentration. In this study, we evaluated the efficacy and safety of lidose-isotretinoin taken without food by patients with severe recalcitrant nodular acne, as well as assessed their quality of life. Primary objective during the 20-week active treatment period (ATP) was to evaluate the QoL of patients taking lidose-isotretinoin twice daily (bid) without food. Secondary objectives during the ATP were to evaluate the efficacy and safety of lidose-isotretinoin taken twice-daily without food.
Methods: This was a Phase IV, multicenter, single-arm, open-label study conducted in the United States in patients with severe recalcitrant nodular acne (NCT02457520) consisting of two phases: a 20-week (5-month) open-label ATP and a 104-week post-treatment period. Patients were included in the study if they were 12 to 45 years of age with recalcitrant acne severe enough for isotretinoin treatment, including five or more facial nodules. Included patients had no prior exposure to systemic isotretinoin or other systemic retinoid and weighed between 40kg and 110kg. Women included in the study could not be pregnant or breastfeeding; women of childbearing potential had to use two forms of effective contraception simultaneously for one month before the trial, during the trial, and for one month after stopping study medication, or commit to continuous abstinence from heterosexual intercourse.
Dosing during the 20-week ATP to attain target cumulative dose of 120mg to 150mg per kilogram of weight was 0.5mg/kg per day divided into two daily doses for four weeks, followed by 1.0 mg/kg per day divided into two daily doses for 16 weeks. Study medication was taken without food (1 hour before or at least 2 hours after ingestion of food or beverages other than water). Primary efficacy endpoint was the change from baseline to the end of treatment (EOT) in the Acne-QoL score, assessed on a graded scale (overall and by domain). Domains included self-perception, role-social, role-emotional, and acne symptoms. Secondary efficacy endpoints included monthly change from baseline in Acne-QoL scores (overall and by domain) and lesion counts during the ATP and change from baseline to EOT in Investigator’s Global Assessment (IGA) scores. Efficacy evaluation was conducted using the intent-to-treat (ITT) population. Overall Acne-QoL score, each domain score, and the changes from baseline for these scores were summarized using descriptive statistics. Differences between baseline and postbaseline values were analyzed using paired t-tests. Descriptive statistics are provided for mean percentage change from baseline value for inflammatory, noninflammatory, and total lesion counts. Differences between baseline and postbaseline values were analyzed using paired t-tests. Descriptive statistics are provided for IGA observed values.
Results: A total of 201 patients (mean age: 18.7 [range: 12–45] years) were enrolled in the study at 21 sites. Eighty-five percent (n=170/201) of patients completed the 20-week ATP. There was a significant increase in standard deviation (SD) Acne-QoL from baseline to EOT (61.4 [28.4] vs. 99.0 [19.8], P<0.0001). All four domains (self-perception, role-social, role-emotional, acne symptoms) were significantly improved over the course of treatment, with positive improvements beginning at Week 4. Mean (SD) percentage change in inflammatory (-87.2 [22.5]) and noninflammatory lesion (-83.2 [30.3]) counts from baseline to EOT were significant (P<0.0001).
Mean IGA scores improved from baseline by approximately 3.0 points at EOT. A total of 286 adverse events (AEs) was reported in 60.2 percent of patients (121/201). The most common AEs were dry skin (10.9%), dry lips (10.4%), and cheilitis (9.0%)
A total of 166 treatment-related AEs was reported in 46.3 percent of patients (93/201). Twelve severe AEs were reported; five were considered to be treatment-related (nausea [n=2], increased blood cholesterol [n=1], liver function test abnormal [n=1], and headache [n=1]). Psychiatric AEs occurred in 17 patients (8.5%). The psychiatric events reported were depression (4.0%), insomnia (1.0%), and anxiety (1.0%). Abnormal laboratory results occurred in 11 patients (5.5%), including increases in blood triglycerides (3.5%), alanine aminotransferase (1.5%), aspartate aminotransferase (1.5%), and blood cholesterol (1.5%). One serious AE was reported: diabetes mellitus on Study Day 127, severe in intensity and unlikely related to study treatment. Eight patients discontinued the study due to AE (psychiatric events [n=5] and abnormalities in laboratory test results [n=3]). Six additional patients had study drug withdrawn for an AE (psychiatric events [n=4], migraine [n=1], and diabetes mellitus [n=1]).
Conclusion: Twice-daily use of lidose-containing isotretinoin taken without food improved QoL over the 20-week treatment period, with improvement seen as early as Week 4. Clinical efficacy was also demonstrated. AEs were generally consistent with the known safety profile for isotretinoin.
Funding/Disclosures: This study was funded by Sun Pharmaceutical Industries, Inc. Andrea Zaenglein has served as a consultant for Ranbaxy/Sun Pharmaceutical Industries, Inc. James Del Rosso has served as a consultant, speaker, and research investigator for Sun Pharmaceutical Industries, Inc.