What are the benefits of this drug (results of trials used to assess efficacy)?

The tables below show the efficacy assessment based on the change in sleep onset and sleep maintenance for the patients in individual trials.

Table 1. Primary and Secondary Efficacy Results for Change from Baseline in Sleep Onset and Sleep Maintenance at 6 Months in Patients with Insomnia (Trial 1)

^{ITT (intention to treat); sSOL (subjective sleep onset latency); SD (standard deviation); LS (least squares); SE (standard error); CI (unadjusted confidence interval); sSEF (subjective sleep efficiency); sWASO (subjective wake after sleep onset)}

^{a For the sleep onset sSOL endpoint, the mean refers to geometric mean, which was used due to the approximately log normal distribution of the outcomes; SD for the geometric mean is calculated as GM*SD (log transformed sSOL); SE for the least squares geometric mean is calculated in the same way as the SD.}

^{b For the sleep onset sSOL endpoint, treatment effect refers to the ratio of [Month 6 sSOL / Baseline sSOL] for DAYVIGO versus placebo, such that a smaller ratio corresponds to a greater improvement.}

^{c Treatment effect refers to the treatment difference between DAYVIGO versus placebo, such that a larger value for sSEF and smaller value for sWASO correspond to greater improvement.}

^{* Doses that were statistically significantly superior (p<0.05) to placebo after multiplicity adjustment.}

Table 2. Primary and Secondary Efficacy Results for Change from Onset and Sleep Maintenance at 1 Month in Patients with Insomnia (Trial 2)

^{ITT (intention to treat); LPS (latency to persistent sleep); SD (standard deviation); LS (least squares); SE (standard error); CI (unadjusted confidence interval); SEF (sleep efficiency); WASO (wake after sleep onset)}

^{a For the sleep onset LPS endpoint, the mean refers to geometric mean, which was used due to the approximately log normal distribution of the outcomes; SD for the geometric mean is calculated as GM*SD(log transformed LPS); SE for the least squares geometric mean is calculated in the same way as the SD.}

^{b For the LPS endpoint, treatment effect refers to the ratio of [Day 29/30 LPS / Baseline LPS] for DAYVIGO versus placebo, such that a smaller ratio corresponds to a greater improvement.}

^{c Treatment effect refers to the treatment difference between DAYVIGO versus placebo, such that a larger value for SEF and smaller value for WASO correspond to greater improvement.}

^{* Doses that were statistically significantly superior (p<0.05) to placebo after multiplicity adjustment.}

DAYVIGO Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age groups?

The figures below show subgroup analyses based on primary endpoints in each trial. Some subgroups are small, limiting interpretation of these findings. In subgroup analyses on two key secondary endpoints (SEF and WASO) in Trial 2 (not shown here), the subgroups generally had effects favoring DAYVIGO.

Figure 4. LSGM Treatment Ratio (Active/Placebo) with 95% CI in sSOL by Subgroup, Trial 1

^{LSGM= least squares geometric mean; CI=confidence interval; sSOL= subject sleep onset latency; F= female; M=male}

Adapted from FDA Review

Figure 5. LSGM Treatment Ratio (Active/Placebo) with 95% CI in LPS by Subgroup, Trial 2

^{LSGM=least squares geometric mean; CI= confidence interval; LPS= latency to persistence sleep; F= female; M=male}

Adapted from FDA Review

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes the adverse reactions that occurred during the first 30 days in the pooled population from the two clinical trials.

Table 3. Adverse Reactions Reported in ≥ 2% of DAYVIGO-Treated Patients and at a Greater Frequency than Placebo-Treated Patients During the First 30-days of Trials 1 and 2

^{* Combines preferred terms somnolence, lethargy, fatigue, sluggishness}

DAYVIGO Prescribing Information

Were there any differences in side effects among sex, race and age groups?

The tables below summarize the main adverse events of interest, somnolence and parasomnia, by subgroups. The tables include all patients who received placebo or DAYVIGO in Trial 1, Trial 2, and the 6-month extension of Trial 1, where the all patients received DAYVIGO.

Table 4. Treatment-Emergent Adverse Reaction Somnolence by Subgroup

Table 5. Treatment -Emergent Adverse Reaction Parasomnia by Subgroup

Adapted from FDA Review

Who participated in the trials?

The table below summarizes the demographics for the efficacy population.

Table 6. Demographic Information for the Efficacy Population

How were the trials designed?

The efficacy and safety of DAYVIGO were assessed in adult patients who met DSM-5 criteria for insomnia disorder.  Patients were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials.

In Trial 1, patients were randomized to DAYVIGO 5 mg, DAYVIGO 10 mg, or placebo once nightly for 6 months. The primary endpoint was the mean change from baseline to end of treatment at 6 months for log transformed patient-reported (subjective) sleep onset latency (sSOL), defined as the number of minutes from the time the subject attempted to sleep until they fell asleep.  Sleep maintenance was measured with two secondary endpoints: subjective sleep efficiency (sSEF), the subject’s perception of the proportion of time they were asleep while in bed, and sWASO, the number of minutes awake between the onset of sleep and wake time.  All endpoints were measured by a sleep diary and therefore reflected patients’ perceptions of their sleep.

In Trial 2 women 55 years and older and men 65 years and older were randomized to DAYVIGO 5 mg, DAYVIGO 10 mg, placebo, or an active comparator once nightly for one month. The primary endpoint was the mean change in log transformed latency to persistent sleep (LPS) from baseline to end of treatment (Days 29/30). LPS was defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness. The secondary endpoints were the mean change from baseline to end of treatment (Days 29/30) in sleep efficiency (SEF) and wake after sleep onset (WASO).  In contrast to Trial 1, all endpoints were measured using overnight polysomnography monitoring.