Results of a Phase III, Double-Blind, Randomized, Parallel-Group, Non-Inferiority Study Evaluating the Safety and Efficacy of Isotretinoin-Lidose in Patients With Severe Recalcitrant Nodular Acne
June 2014 | Volume 13 | Issue 6 | Original Article | 665 | Copyright © June 2014
Guy F. Webster MD PhD,a James J. Leyden MD,b and Jason A. Gross PharmDc
aDepartment of Dermatology, Jefferson Medical College, Philadelphia, PA
bDepartment of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA
cCipher Pharmaceutical Inc., Mississauga, Ontario, Canada
OBJECTIVE: Evaluate the safety profiles of isotretinoin-Lidose and food-dependent generic isotretinoin in the largest clinical study with isotretinoin—925 randomized patients from 49 study sites. Determine if the efficacy of this new formulation is noninferior to an existing isotretinoin.
METHODS: Multicenter, double-blind, randomized, parallel-group, noninferiority trial. Study medication was taken with meals twice daily for 20 weeks. Patients were followed for 4 weeks after the last dose. Safety evaluations included recordings of adverse events, assessments for depression, anxiety, emergent psychotic symptoms, and suicidal ideation/behavior, as well as DEXA and X-ray evaluations and changes in bone age. Two co-primary efficacy outcomes were measured to assess noninferiority: a) change in total nodular facial and truncal lesion count at from baseline to week 20 and b) percentage of patients who experienced at least 90% reduction in nodular facial and truncal lesion count from baseline to week 20.
LIMITATIONS: Although isotretinoin-Lidose can be taken without meals, it was given with food because the absorption of both formulations in the study had to be similar to detect noninferiority.
RESULTS: The safety profile of the 2 formulations was comparable. Criteria for noninferiority for both co-primary efficacy outcomes were met based on predetermined margins.
CONCLUSION: Safety and efficacy of isotretinoin-Lidose is similar and noninferior to food-dependent generic isotretinoin, respectively.
J Drugs Dermatol. 2014;13(6):665-670.