The objective was to evaluate the dose-response relationship of Daridorexant ( Quviviq ), a new dual orexin receptor antagonist, on sleep variables in subjects with insomnia disorder.
Adults ( 64 years or less ) with insomnia disorder were randomized ( 1:1:1:1:1:1 ) to receive daily oral placebo, Daridorexant ( 5, 10, 25, or 50mg ), or 10mg Zolpidem ( Stilnox ) for 30 days.
The primary efficacy outcome was the change in wake time after sleep onset from baseline to days 1 and 2.
Secondary outcome measures were change in latency to persistent sleep from baseline to days 1 and 2, change in subjective wake time after sleep onset, and subjective latency to sleep onset from baseline to week 4.
Safety was also assessed.
Of 1,005 subjects screened, 359 ( 64% female ) were randomized and received 1 dose or more.
A significant dose-response relationship ( multiple comparison procedure-modeling, 2-sided p less than 0.001 ) was found in the reduction of wake after sleep onset and latency to persistent sleep from baseline to days 1 and 2 with Daridorexant.
These reductions were sustained through to days 28 and 29 ( p = 0.050 and p = 0.042, respectively ).
Similar dose-dependent relationships were observed for subjective wake after sleep onset and subjective latency to sleep onset.
The incidence of treatment-emergent adverse events was 35%, 38%, 38%, and 34% in subjects treated with 5, 10, 25, and 50mg Daridorexant, respectively, compared with 30% for placebo, and 40% for 10mg Zolpidem.
There were no clinically relevant treatment-related serious adverse events.
Four subjects withdrew due to adverse events.
In conclusion, Daridorexant has induced a dose-dependent reduction in wake time after sleep onset in subjects with insomnia disorder. ( Xagena )
Dauvilliers Y et al, Ann Neurol 2020; 87: 347-356