Single therapeutic and supratherapeutic doses of corifollitropin alfa, a sustained follicle stimulant, do not prolong the QTcF-interval in healthy postmenopausal volunteers

摘要

Objective: Corifollitropin alfa (Elonva (R)) is the first hybrid follicle-stimulating hormone molecule with demonstrated sustained follicle-stimulating activity after a single subcutaneous injection. This trial evaluated if corifollitropin alfa is associated with QT/QTc prolongation and/or proarrhythmic potential as compared to placebo in healthy post-menopausal women. Materials: Participants were healthy, postmenopausal women. Study treatments were corifollitropin alfa 150 mu g, corifollitropin alfa 240 mu g, and moxifloxacin 400 mg with placebo. Methods: This randomized, double-blind, double-dummy, 4-period crossover trial compared single doses of corifollitropin alfa 150 mu g (therapeutic dose), corifollitropin alfa 240 mu g (supratherapeutic dose), and moxifloxacin 400 mg (positive control) with placebo. Corifollitropin alfa was administered on day 1 and moxifloxacin on day 2. Results: The largest time-matched mean QTcF difference versus placebo for the therapeutic dose of corifollitropin alfa was 1.4 ms (upper limit of 1-sided 95% confidence interval (UL 95% CI) = 3.4 ms), and for the supratherapeutic dose was 1.2 ms (UL 95% CI = 3.6 ms). Conclusions: For both the therapeutic and the supratherapeutic dose of corifollitropin alfa and at all timepoints, the UL 95% Cl for the time-matched QTcF differences compared with placebo was below 10 ms, the threshold of relevance defined by the ICH E14 guideline. Single therapeutic and supratherapeutic doses of corifollitropin alfa are not associated with clinically relevant QT/QTc-interval prolongation in healthy post-menopausal women.