The Effects of Elinzanetant on Simulated Driving Performance in Healthy Women: A Randomized Phase I Study

Abstract

Elinzanetant is a dual neurokinin–1 and –3 receptor antagonist in development for treating vasomotor symptoms associated with menopause. Its central nervous system action and bedtime dosing could produce next-morning residual effects that impact safety when driving. We therefore conducted a randomized, double-blind, placebo- and active-controlled, four-period, crossover study to assess the effect of elinzanetant on next-morning simulated driving performance. Sixty-four healthy women aged 40–65 years with regular sleep patterns were randomized to receive elinzanetant 120 mg, elinzanetant 240 mg, zopiclone 7.5 mg, or placebo for 5 days in one of four sequences. The primary endpoint assessed participant's ability to maintain a consistent position within the lane, measured using standard deviation of lateral position (SDLP). Secondary assessments included lane exceedance, cornering speeds, and treatment-emergent adverse events (TEAEs), among others. The least squares mean SDLP for both doses of elinzanetant on Day 2 and Day 6 were significantly below the non-inferiority margin of 4.4 cm (p < 0.0001). Small increases in SDLP with both doses versus placebo were observed on Day 2 but not on Day 6. Secondary assessments were not significantly different to placebo, apart from lane exceedances and cornering speed threshold exceedances. TEAEs were reported in 84% of participants; most were mild, and there was no increase in TEAE frequency with the 240 mg dose. Our study demonstrated no clinically relevant next-morning residual effects following bedtime elinzanetant dosing and confirmed the elinzanetant benefit: risk balance was not adversely impacted by somnolence or fatigue the following morning.

Trial Registration: ClinicalTrials.gov identifier: NCT06219902