RESUMO
RATIONALE: OT329 SOLIS is a generic candidate for the branded asthma treatment, ADVAIR DISKUS (fluticasone propionate/salmeterol xinafoate), and, as such, the manufacturer is required to provide evidence of clinical "bioequivalence" as a condition for regulatory approval. OBJECTIVES: The objective of the current study was to determine if SOLIS and DISKUS provided bioequivalent improvements in lung function at two time points: Day 1 and Week 4. METHODS: This study was a randomized, multiple-dose, placebo-controlled, parallel-group design conducted in the United States (NCT02260492) with a 2-week run-in followed by a 4-week treatment period. Consenting patients were randomized to treatment with OT329 SOLIS 100/50, ADVAIR DISKUS 100/50, or placebo. Lung function was measured predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after the first dose to test equivalence of the ß-agonist salmeterol component based on FEV1 area under the curve (0-12 h). After 4 weeks of twice-daily dosing, trough (predose) FEV1 was measured to evaluate equivalence of the fluticasone propionate corticosteroid component. Bioequivalence was concluded if the 90% confidence interval (CI) for the ratio of the products fell within 80-125%. MEASUREMENTS AND MAIN RESULTS: Of the 1,524 screened, 879 patients with asthma were randomized to treatment (n = 418 SOLIS, 419 DISKUS, 42 placebo). OT329 SOLIS and ADVAIR DISKUS were bioequivalent at Day 1, with an FEV1 area under the curve (0-12 h) test/reference ratio of 108% (90% CI = 94-122%). Likewise, the products were bioequivalent at Week 4 with a trough FEV1 test/reference ratio of 105% (90% CI = 90-119). Both active treatments were superior to placebo (P < 0.05) at both time points. CONCLUSIONS: The data support a conclusion of clinical bioequivalence of OT329 SOLIS to ADVAIR DISKUS. Clinical trial registered with www.clinicaltrials.gov (NCT02260492).
