SAGE-217, administered as a single dose at either 30 or 45 mg, significantly improved sleep efficiency (SE), the primary endpoint of the trial, to a median of 85 percent (30 mg; p<0.0001) and 88 percent (45 mg; p<0.0001), respectively, compared with a median SE of 73 percent for placebo.
SAGE-217 also demonstrated statistically significant improvements in total sleep time as well as sleep maintenance as measured by time spent awake after sleep onset, although there was not a significant impact on sleep onset in this model as measured by latency to persistent sleep.
SAGE-217 was generally well tolerated and all adverse events (AEs) were mild, with no serious AEs or AEs leading to discontinuation. Based on these positive results, Sage expects to initiate clinical development of SAGE-217 in disorders of sleep in 2018.
Sage Therapeutics CEO Jeff Jonas said: “Disturbances of sleep have a profound impact on the quality of life for many individuals, whether occurring as a primary disorder or as associated with other illness.
“There is a significant need to create an improved patient experience for the treatment of sleep dysfunction, and our work with the GABA mechanism identified an opportunity to develop a potential solution. These findings support the unique potential of SAGE-217 across a variety of psychiatric and neurological disorders with unifying focus on related symptoms, including disorders of mood, sleep and motor function.”
Sage Therapeutics chief research officer Jim Doherty said: “Key to the experimental medicine capability at Sage is translating insights between compounds and indications for better odds of success across the pipeline.
“Our evaluation of SAGE-217 in multiple clinical trials, across several indications, suggests that the drug’s mechanism of action may rebalance fundamental brain circuitry, therefore supporting SAGE-217’s development across a broad variety of disorders. These findings suggest that SAGE-217 has the potential to assist sleep maintenance, and we were pleased with the tolerability demonstrated for both doses in this trial.”
Top-line Trial Results
Sleep Efficiency (primary endpoint): the percentage of time in bed spent asleep, as determined by polysomnography.
SAGE-217, 30 and 45 mg, administered as a single dose significantly improved Sleep Efficiency (SE) to a median of 84.64% (p<0.0001) and 87.55% (p<0.0001), respectively compared with a median SE of 72.92% for placebo.
Wake After Sleep Onset (secondary endpoint): total wake time, in minutes, from persistent sleep onset to lights-on, as determined by polysomnography.
SAGE-217, 30 and 45 mg, decreased time of wake after sleep onset (WASO) to a median of 55.0 minutes (p<0.0001) and 42.5 minutes (p<0.0001), respectively, compared with 113.0 minutes for subjects on placebo.
Total Sleep Time (secondary endpoint): duration of total sleep time (non-REM and REM) from lights-off to lights-on during recording with polysomnography.
SAGE-217 increased total sleep time, compared with a median of 350.00 min in subjects treated with placebo, to 406.25 (p<0.0001) and 420.25 (p<0.0001) minutes, respectively for the 30 and 45 mg doses of SAGE-217.
Latency to Persistent Sleep (secondary endpoint): duration in minutes from lights-off to the first epoch of 20 consecutive non-wake epochs, as determined by polysomnography.
Compared with placebo, SAGE-217 did not have a significant impact on latency to persistent sleep (p=0.7049) with either dose.
Safety and Tolerability: SAGE-217 was generally well tolerated in this study. Adverse event rates were low across all dose groups (4.8% SAGE-217 45 mg, 11.4% SAGE-217 30 mg and 9.8% placebo) and all adverse events (AEs) were mild. There were no serious AEs and no AEs leading to discontinuation.