A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, and Efficacy of SAGE-217 Compared to Placebo in Adult Subjects With Comorbid Major Depressive Disorder and Insomnia
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Major Depressive Disorder
- Sponsor
- Biogen
- Enrollment
- 87
- Locations
- 1
- Primary Endpoint
- Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is a randomized, double-blind, placebo-controlled study of the safety, tolerability, and efficacy of SAGE-217 compared to placebo in adult participants with comorbid major depressive disorder (MDD) and insomnia.
Detailed Description
This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant had a diagnosis of MDD as diagnosed by structured clinical interview for diagnostic and statistical manual of mental disorders, fifth edition, clinical trials version (SCID-5-CT), with symptoms that have been present for at least a 4-week period.
- •Participant had a diagnosis of Insomnia that is confirmed at screening based on the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) diagnostic criteria using the SCID-5-CT.
- •Participant had an Insomnia Severity Index (ISI) score greater than or equal to (\>=) 15 (moderate to severe insomnia).
- •Participant had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥28 prior to dosing and a Hamilton Rating Scale for Depression (HAM-D) total score of ≥20.
Exclusion Criteria
- •Participant had attempted suicide associated within the current episode of MDD.
- •Participant had onset of the current depressive episode during pregnancy or 4 weeks postpartum, or the participant had presented for screening during the 6-month postpartum period.
- •Participant had a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder.
- •Participant had a medical history of seizures.
- •Participant had active psychosis per Investigator assessment.
Arms & Interventions
Placebo
Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out \[polysomnography (PSG)\] on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
Intervention: Placebo
SAGE-217
Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 milligrams (mg) capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
Intervention: SAGE-217
Outcomes
Primary Outcomes
Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14
Time Frame: Baseline and Days 13, 14
Sleep Efficiency (SE) is the percentage of time in bed spent asleep, determined during an 8-hour overnight PSG recording. The PSG measures the physiological process of sleep by monitoring body functions including brain waves, eye movements, muscle activity or skeletal muscle activation, heart rhythm, blood oxygen saturation, and breathing functions. Stages of sleep include rapid eye movement (REM), non-rapid eye movement (NREM), NREM stage 1 (N1), NREM stage 2 (N2), and NREM stage 3 (N3), scored through evaluation of the electroencephalogram (EEG) signal. The average of 2 nights' PSG measurements at Days 13 and 14 is reported in this outcome measure.
Secondary Outcomes
- Change From Baseline in REM Density(Baseline and Day 14 (EODBT))
- Change From Baseline in CSD-C Parameter: Subjective Sleep Quality (sSQ)(Baseline and Day 15)
- Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)(Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording)
- Change From Baseline in Latency to the First Period and Each Subsequent Period (Periods 2, 3, 4) of REM Sleep(Baseline and Day 14 (EODBT))
- Change From Baseline in REM Activity (REMA)(Baseline and Day 14 (EODBT))
- Change From Baseline in Consensus Sleep Diary - Core (CSD-C) Parameters(Baseline and Day 15)
- Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale(Baseline and Day 15)
- Change From Baseline in Total Sleep Time (TST)(Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording)
- Change From Baseline in Latency to Persistent Sleep (LPS)(Baseline and Day 14 (EODBT))
- Change From Baseline in Number of Awakenings (NAW)(Baseline and Day 14 (EODBT))
- Change From Baseline in Percentage of N1, N2, N3 Stages, and REM Sleep Duration(Baseline and Day 14 (EODBT))
- Change From Baseline in Mean Duration of Awakenings(Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording)
- Change From Baseline in Duration of Stage N1, N2, N3, and REM Sleep (in Minutes)(Baseline and Day 14 (EODBT))
- Change From Baseline in Insomnia Severity Index (ISI) Score(Baseline and Day 15)
- Mean Score of the Clinical Global Impression - Improvement (CGI-I) Scale(Day 15)
- Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score(Baseline and Day 15)
- Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Score(Baseline and Day 15)
- Number of Participants With Potentially Clinically Significant Vital Signs(Screening up to last follow-up visit (approximately 72 days))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of drug up to last follow-up visit (approximately 72 days))
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities(Screening up to last follow-up visit (approximately 72 days))
- Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities(Screening up to last follow-up visit (approximately 72 days))
- Number of Participants With Suicidal Ideation and Suicidal Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)(Screening up to last follow-up visit (approximately 72 days))
- Change From Baseline in the Withdrawal Symptoms as Measured by the Physician Withdrawal Checklist (PWC-20) Total Score(Baseline, Days 18, 22, 28, 35 and 42)