Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objectives:</jats:title> <jats:p>To evaluate the safety, pharmacokinetics, and preliminary efficacy of NT-814, a dual neurokinin 1,3 antagonist, in postmenopausal women with vasomotor symptoms (hot flashes).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>We completed a double-blind, randomized, placebo-controlled trial in three US clinical research units in 76 postmenopausal women with moderate/severe hot flashes. Participants were randomized to 14 days of once-daily NT-814 or placebo within each of four sequential dose cohorts; 50, 100, 150, and 300 mg. Participants completed diaries of hot flash frequency and severity and waking due to night sweats before (baseline) and during treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>All prespecified efficacy parameters (24-h hot flash frequency and severity, frequency of waking due to night sweats) decreased in all groups (including placebo). Mean reduction from baseline at week 2 in moderate/severe hot flash frequency was 37% in the placebo group and, respectively, 24% (<jats:italic toggle="yes">P</jats:italic> = 0.048 vs placebo), 59% (<jats:italic toggle="yes">P</jats:italic> = 0.155), 84% (<jats:italic toggle="yes">P</jats:italic> < 0.001) and 66% (<jats:italic toggle="yes">P</jats:italic> = 0.022) in the 50 mg, 100 mg, 150 mg, and 300 mg NT-814 groups; in waking due to night sweats reduction was 20% (<jats:italic toggle="yes">P</jats:italic> = 0.059), 55% (<jats:italic toggle="yes">P</jats:italic> = 0.135), 81% (<jats:italic toggle="yes">P</jats:italic> < 0.001), and 63% (<jats:italic toggle="yes">P</jats:italic> = 0.031) in the NT-814 groups and 32% in the placebo group. The improvement with NT-814 ≥150 mg was also evident in the first week of treatment. The most common treatment-related adverse events were mild somnolence and headache, more frequently in the 300 mg group. Safety monitoring identified no concerns.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Once-daily NT-814 (≥150 mg/d) resulted in a rapid, marked improvement in hot flashes and waking due to night sweats. No safety concerns were identified. Doses up to 300 mg were well tolerated.</jats:p> </jats:sec>