Sage Therapeutics Announces Positive Results from Placebo-Controlled Trial in a Model of Insomnia Demonstrating Activity on Sleep Parameters and Supporting Development of SAGE-217 as Potential Treatment for Sleep Disorders
– SAGE-217 met primary endpoint of improved sleep efficiency and demonstrated improvements in maintaining sleep compared to placebo –
– Secondary endpoint measures demonstrated clear dose response with statistical significance in total sleep time and time spent awake after sleep onset –
– Data support further development of SAGE-217 in disorders associated with disruption of normal sleep –
“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,” said
“Key to the experimental medicine capability at Sage is translating
insights between compounds and indications for better odds of success
across the pipeline,” said
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
- 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
- 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.
- Comprehensive data, including additional secondary endpoint measures, will be presented at a future scientific conference.
In this double-blind, placebo-controlled crossover study (Treatment Periods 1, 2 and 3), healthy volunteers (n=45) were randomized to receive either 30 mg or 45 mg of SAGE-217 or placebo on three separate visits. Each participant received each dose level and placebo once.
Treatment Period 1 began on Study Day 1 and continued until Study Day 2, using a 5-hour phase advance model of insomnia (lights out and polysomnography recording began five hours (± 30 minutes) prior to participants habitual bedtime). Thirty minutes (±15 minutes) prior to lights out, blinded study drug (SAGE-217 30 mg, SAGE-217 45 mg, or placebo) was administered and participants were required to remain in bed for eight hours. Treatment Period 2 (Visit 4, Study Days 8 to 9) and Treatment Period 3 (Visit 5, Study Days 15 to 16) followed similar procedures.
SAGE-217 is a next generation positive allosteric modulator that targets synaptic and extrasynaptic GABA receptors and has a pharmacokinetic profile intended for daily oral dosing. The GABA system is the major inhibitory signaling pathway of the brain and CNS and contributes significantly to regulating CNS function. SAGE-217 is currently being developed in the treatment of MDD and certain other affective disorders, Parkinson’s disease and sleep disorders.
Various statements in this release concern Sage's future
expectations, plans and prospects, including without limitation: our
expectations regarding the potential for SAGE-217 in the treatment of
sleep disorders, depression and other diseases and disorders; our
statements regarding plans for further development of SAGE-217 and
related activities and the potential for successful development; our
view of the potential of the GABA mechanism and our product candidates,
including SAGE-217, in the treatment of CNS diseases and disorders; and
our views as to the unmet need for additional options in the treatment
of sleep disorders and the potential of SAGE-217 to meet the unmet need.
These forward-looking statements are neither promises nor guarantees of
future performance, and are subject to a variety of risks and
uncertainties, many of which are beyond our control, which could cause
actual results to differ materially from those contemplated in these
forward-looking statements, including the risks that: we may not be able
to successfully demonstrate the efficacy and safety of SAGE-217 or any
of our other product candidates at each stage of development; success in
early stage clinical trials may not be repeated or observed in ongoing
or future studies of SAGE-217 or any of our other product candidates;
ongoing and future clinical results may not support further development
or be sufficient to gain regulatory approval to market SAGE-217 or any
of our other product candidates; we may decide that a development
pathway for one of our product candidates in one or more indications is
no longer feasible or advisable or that the unmet need no longer exists;
decisions or actions of the