Author (year) Groups Studied and Intervention Results and Findings Conclusions
Zammit et al. (2020)[@135915] Elderly patients between 65-85 years old with insomnia were randomly allocated to receive 5 treatments of 5, 10, 25, and 50 mg daridorexant and placebo during 5 treatment periods that lasted 2 nights followed by a washout period of 5-12 days. WASO and LPS were dose-dependently reduced after daridorexant administration (p < 0.0001, p < 0.004). Reductions were statistically significant for daridorexant doses ³ 10 mg (p < 0.025) when compared to placebo. Adverse events were similar to placebo, with the most common being fatigue, nasopharyngitis, gait disturbance, and headache. Daridorexant is well tolerated in the elderly population for the use of insomnia.
Mignot et al. (2022)[@135940] Two randomized, double-blind, placebo-controlled phase 3 trials in adults 18 years old were randomly assigned to 25 or 50 mg of daridorexant or placebo in study 1 and 10 or 25 mg of daridorexant or placebo in study 2. Study 1: WASO and LPS were significantly reduced in patients taking 50 mg daridorexant compared to the placebo group after month 1 (p < 0.0001, p < 0.0001) and 3 (p < 0.0001, p < 0.0001). Additionally, 50 mg daridorexant had improved self-reported sleep time at month 1 and 3 (p < 0.0001, p < 0.0001) and IDSIQ sleepiness domain scores at month 1 and 3 (p < 0.0001, p < 0.0002) compared to placebo. Participants taking 25 mg daridorexant had improved self-reported TST at months 1 and 3 (p < 0.0013, p < 0.033), but not in IDSIQ sleepiness domain
Study 2: WASO was significantly reduced in patients taking 25 mg daridorexant after month 1 (p < 0.0001) and 3 (p < 0.0028), but no differences in LPS were observed. Additionally, patients reported improvement in TST but not in IDSIQ sleepiness domain scores. There were no significant differences between 10 mg daridorexant and placebo for WASO, LSP, TST, or IDSIQ sleepiness domain scores.
50 mg daridorexant improved sleep outcomes and daytime functioning, while 25 mg daridorexant improved sleep outcomes in patients with insomnia disorder when compared to placebo.
Boof et al. (2021)[@135947] Randomized, double-blind, placebo-controlled, two-period crossover study involving 28 patients > 18 years old that were randomized to receive 50 mg daridorexant followed by placebo or vice versa. There was no effect of 50 mg daridorexant on AHI during TST when compared to placebo with a 90% CI of 0.74 (-1.43, 2.92). Time spent with SpO2 < 90%, < 85%, and < 80% with 50 mg daridorexant was comparable to placebo. Daridorexant significantly increased TST by 39.6 minutes (p < 0.007) after a single dose. There was no significant difference in total arousal indices when compared to placebo. Additionally, repeated administration of daridorexant 50 mg significantly increased SEI by 8.04% (p = 0.0002), reduced WASO by 31 minutes (p = 0.004), and shortened LPS by 19.8 minutes that was not considered statistically significant (p = 0.12). Single and repeated doses of 50 mg daridorexant do not impair nighttime respiratory function in patients with mild to moderate COPD.
Schilling et al. (2021)[@135944] Randomized, double-blind, placebo-controlled, four-period crossover study involving 36 healthy subjects who received 50 or 200 mg daridorexant, 400 mg moxifloxacin, or placebo to investigate the effect on QT interval duration. Baseline and placebo corrected QT interval was > 5 ms following moxifloxacin administration (p < 0.01). When daridorexant was administered, QT interval was 1.40 ms with the 50 mg dose and 1.84 ms with the 100 mg dose. Lack of QT prolongation with daridorexant was further confirmed using secondary by-time point analysis and categorical outlier analysis. Daridorexant does not impair cardiac repolarization via absence of QT prolongation, making it well tolerated for individuals with insomnia.
Muehlan et al. (2020)[@135943] Double-blind, placebo-controlled, randomized, single-ascending dose study in elderly patients aged 65-80 years old. Patients were randomly assigned to take 5, 15, or 25 mg of daridorexant or placebo in the morning and an additional 10 subjects received 25 mg daridorexant in the evening to assess the pharmacokinetics, pharmacodynamics, and tolerability of daridorexant in elderly patients. Median time to maximum concentration of daridorexant was found to be about 1 h and the elimination half-life was 8.5-9.8 hours. No pharmacodynamic effects were noted with the 5 mg dose when compared to placebo. The 15 mg dose of daridorexant reduced the saccadic peak velocity while all other variables were similar to placebo. All pharmacodynamic parameters were observed with the 25 mg dose of daridorexant when compared to placebo, however there was no difference to placebo 8-12 hours after administration. Daridorexant is well-tolerant in the elderly population for the use of insomnia and have very little next-day effects that are a common complaint with other insomnia medications.
Dauvilliers et al. (2020)[@135942] Randomized, double-blind, placebo-controlled, and active-controlled dose-response phase 2 study involving patients aged 18-64 who met the DSM-V criteria for insomnia disorder. Patients received placebo, 5, 10, 25, or 50 mg daridorexant, or 10 mg zolpidem and LSO, WASO, and adverse effects were recorded. Significant dose-response relationship (p < 0.011) was found in reduction of WASO and LASP from baseline to days 1 and 2 with daridorexant when compared to placebo. Incidence of adverse events was 35%, 38%, 38%, and 34% in subjects treated with 5, 10, 25, and 50 mg daridorexant, respectively, compared with 30% for placebo and 40% for 10 mg zolpidem. When compared to placebo and zolpidem, daridorexant showed significant improvement in sleep induction and maintenance with a minimal side effect profile and insignificant potential for residual next-morning sleepiness.
Ufer et al. (2022)[@135939] Randomized, double-blind, double-dummy, placebo- and active-controlled 6 period crossover study that included healthy patients aged 18-55 who reported being a recreational user of sedatives defined by at least 10 lifetime recreational uses and at least one occasion within 12 weeks prior to screening. Patients were randomly given 50, 100, or 150 mg of daridorexant, 150 mg suvorexant, 30 mg zolpidem, or placebo and the drug-liking VAS was assessed after over 24 hours. The drug-liking VAS of 50 mg daridorexant was significantly lower when compared to suvorexant and zolpidem (p < 0.0001). However, 100 mg and 150 mg daridorexant had similar drug-liking VAS when compared to suvorexant and zolpidem and increased with each dose when compared to placebo. Higher doses of daridorexant are comparative to suvorexant and zolpidem concerning the potential for abuse, making it an important factor to consider when considering daridorexant for the use of insomnia.
Muehlan et al. (2020)[@135945] Randomized, placebo- and active-controlled, 4-way crossover study including 60 healthy patients aged 50-79. Participants were randomized to receive 50 or 100 mg daridorexant, 7.5 mg zopiclone, or placebo and then SDLP was assessed to determine drug effect on driving performance. SDLP was significantly increased with 7.5 mg zopiclone when compared to placebo on day 2 and day 5. SDLP was significantly increased by 2.19 with 50 mg daridorexant and 4.43 with 100 mg daridorexant on day 2 when compared to placebo. In contrast, SDLP values for both doses were significantly below the threshold of impairment (2.6 cm) and similar to the placebo. Daridorexant can potentiate impaired driving performance after initial dose but not after repeated dosing; therefore, patients should be cautioned about driving when using daridorexant for insomnia.