OBJECTIVE: To evaluate polysomnographic (PSG) and self-reported measures of the efficacy and safety of EVT 201 in patients with primary insomnia. PATIENTS AND METHODS: Following clinical and PSG screening, 75 patients (mean age: 45.1+/-11.2 y; 50 f, 25 m) meeting DSM-IV criteria for primary insomnia entered this crossover study and were randomly assigned to double-blind treatment sequences of 1.5 mg or 2.5 mg EVT 201, or placebo using a balanced Latin square design. For each study condition study medication was administered on two consecutive nights and PSG and self-reported data were collected. Safety assessments included physical examination, clinical laboratory measures, electrocardiogram, documentation of adverse events, and the digit symbol substitution test (DSST) and self-reported sleepiness/alertness ratings to detect residual sedation. Data were collected at five US sleep laboratories. Efficacy analyses were performed for the 67 patients completing the study. Safety analyses included all 75 randomized patients. RESULTS: On PSG measures compared to placebo, EVT 201 1.5 mg and 2.5 mg increased total sleep time (TST; 33.1, 45.0 min; both p<0.0001), reduced wake after sleep onset (WASO; -16.7, -25.7 min; both p<0.0001), reduced latency to persistent sleep (LPS; -17.0, -20.7 min; both p<0.0001), and reduced the number of awakenings (-1.2, -2.6; both p<0.0001). Significant reduction of wake time was seen with 1.5 mg during each of the first three quarters of the night (p<0.0001-0.002), and with 2.5 mg in all four quarters (p<0.0001-0.0005). Both doses also improved all key self-reported measures of sleep including total sleep time (rTST; 51.9, 51.1 min; both p<0.0001), wake after sleep onset (rWASO; -29.3, -29.6 min; both p<0.0001), sleep latency (rSL; -24.0 min, p<0.004; -25.1 min, p<0.0002), and number of awakenings (rNAW; -1.1, -1.2; both p<0.0001). Sleep quality was also improved by both doses. Self-rated sleepiness in the morning did not differ from placebo for either dose; however, there was a small negative effect on the DSST for both doses. Both doses had similar effects on sleep architecture including an increase in Stage 2 sleep and REM latency and a small, but significant decrease in REM (REM -5.7, -8.3 min; p=0.0175, p=0.0006). No effect on other sleep architecture parameters, including SWS, was seen. EVT 201 was well tolerated. No serious or unexpected adverse events were reported. CONCLUSION: This first study of EVT 201 in adult patients with primary insomnia demonstrated improved measures of sleep onset and sleep maintenance, including during the third and fourth quarters of the night. Adverse events were infrequent and all were mild to moderate in severity.
RCT Entities:
OBJECTIVE: To evaluate polysomnographic (PSG) and self-reported measures of the efficacy and safety of EVT 201 in patients with primary insomnia. PATIENTS AND METHODS: Following clinical and PSG screening, 75 patients (mean age: 45.1+/-11.2 y; 50 f, 25 m) meeting DSM-IV criteria for primary insomnia entered this crossover study and were randomly assigned to double-blind treatment sequences of 1.5 mg or 2.5 mg EVT 201, or placebo using a balanced Latin square design. For each study condition study medication was administered on two consecutive nights and PSG and self-reported data were collected. Safety assessments included physical examination, clinical laboratory measures, electrocardiogram, documentation of adverse events, and the digit symbol substitution test (DSST) and self-reported sleepiness/alertness ratings to detect residual sedation. Data were collected at five US sleep laboratories. Efficacy analyses were performed for the 67 patients completing the study. Safety analyses included all 75 randomized patients. RESULTS: On PSG measures compared to placebo, EVT 201 1.5 mg and 2.5 mg increased total sleep time (TST; 33.1, 45.0 min; both p<0.0001), reduced wake after sleep onset (WASO; -16.7, -25.7 min; both p<0.0001), reduced latency to persistent sleep (LPS; -17.0, -20.7 min; both p<0.0001), and reduced the number of awakenings (-1.2, -2.6; both p<0.0001). Significant reduction of wake time was seen with 1.5 mg during each of the first three quarters of the night (p<0.0001-0.002), and with 2.5 mg in all four quarters (p<0.0001-0.0005). Both doses also improved all key self-reported measures of sleep including total sleep time (rTST; 51.9, 51.1 min; both p<0.0001), wake after sleep onset (rWASO; -29.3, -29.6 min; both p<0.0001), sleep latency (rSL; -24.0 min, p<0.004; -25.1 min, p<0.0002), and number of awakenings (rNAW; -1.1, -1.2; both p<0.0001). Sleep quality was also improved by both doses. Self-rated sleepiness in the morning did not differ from placebo for either dose; however, there was a small negative effect on the DSST for both doses. Both doses had similar effects on sleep architecture including an increase in Stage 2 sleep and REM latency and a small, but significant decrease in REM (REM -5.7, -8.3 min; p=0.0175, p=0.0006). No effect on other sleep architecture parameters, including SWS, was seen. EVT 201 was well tolerated. No serious or unexpected adverse events were reported. CONCLUSION: This first study of EVT 201 in adult patients with primary insomnia demonstrated improved measures of sleep onset and sleep maintenance, including during the third and fourth quarters of the night. Adverse events were infrequent and all were mild to moderate in severity.