A Study to Evaluate the Safety, Tolerability, and Efficacy of SAGE-217 Compared to Placebo in Adult Participants With Comorbid Major Depressive Disorder (MDD) and Insomnia

November 27, 2023 updated by: Biogen

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

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.

Study Overview

Status

Terminated

Intervention / Treatment

Detailed Description

This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • Sage Investigational Site
      • Rogers, Arkansas, United States, 72758
        • Sage Investigational Site
    • California
      • Garden Grove, California, United States, 92845
        • Sage Investigational Site
      • Oceanside, California, United States, 92056
        • Sage Investigational Site
      • San Diego, California, United States, 92103
        • Sage Investigational Site
      • Temecula, California, United States, 92591
        • Sage Investigational Site
    • Florida
      • Fort Myers, Florida, United States, 33912
        • Sage Investigational Site
      • Hollywood, Florida, United States, 33024
        • Sage Investigational Site
      • Miami Lakes, Florida, United States, 33016
        • Sage Investigational Site
      • North Miami, Florida, United States, 33161
        • Sage Investigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30331
        • Sage Investigational Site
      • Atlanta, Georgia, United States, 30342
        • Sage Investigational Site
      • Decatur, Georgia, United States, 30030
        • Sage Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60634
        • Sage Investigational Site
    • Louisiana
      • Lake Charles, Louisiana, United States, 70629
        • Sage Investigational Site
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Sage Investigational Site
    • Missouri
      • Saint Louis, Missouri, United States, 63141
        • Sage Investigational Site
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Sage Investigational Site
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Sage Investigational Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Sage Investigational Site
    • New York
      • Brooklyn, New York, United States, 11235
        • Sage Investigational Site
      • New York, New York, United States, 10019
        • Sage Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45212
        • Sage Investigational Site
      • Dayton, Ohio, United States, 45417
        • Sage Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73103
        • Sage Investigational Site
    • Oregon
      • Salem, Oregon, United States, 97301
        • Sage Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States, 29407
        • Sage Investigational Site
    • Texas
      • Austin, Texas, United States, 78754
        • Sage Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 62 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. 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.
  3. Participant had an Insomnia Severity Index (ISI) score greater than or equal to (>=) 15 (moderate to severe insomnia).
  4. 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:

  1. Participant had attempted suicide associated within the current episode of MDD.
  2. 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.
  3. Participant had a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder.
  4. Participant had a medical history of seizures.
  5. Participant had active psychosis per Investigator assessment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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.
Administered as capsules.
Experimental: 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.
Administered as capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and Days 13, 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)
Time Frame: 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
WASO is the total wake time (in minutes) calculated from persistent sleep onset to lights-on (final wake time). In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) WASO and in each quarter (for the each 2-hour duration) WASO of the 8-hour PSG recording is reported.
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 Total Sleep Time (TST)
Time Frame: 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
TST is the duration of total sleep time (NREM + REM) (in minutes) from lights off to lights on during PSG recording. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) TST and in each quarter (for the each 2-hour duration) TST of the 8-hour PSG recording is reported.
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)
Time Frame: Baseline and Day 14 (EODBT)
LPS is duration in minutes from lights off to the first epoch of 20 consecutive non-wake epochs.
Baseline and Day 14 (EODBT)
Change From Baseline in Number of Awakenings (NAW)
Time Frame: Baseline and Day 14 (EODBT)
NAW was calculated from the onset of persistent sleep until lights on. An awakening is defined as at least 2 consecutive epochs of wake. Individual awakenings were separated by at least 1 epoch of Stage N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) or REM sleep.
Baseline and Day 14 (EODBT)
Change From Baseline in Mean Duration of Awakenings
Time Frame: 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
An awakening is defined as at least 2 consecutive epochs of wake. Mean duration of awakenings is an arithmetic mean calculated as the sum of duration of all awakenings (in minutes) divided by the number of awakenings. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) mean duration of awakenings and in each quarter (for the each 2-hour duration) mean duration of awakenings is reported.
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)
Time Frame: Baseline and Day 14 (EODBT)
The change in duration (minutes) of NREM sleep stages: N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep time from lights off to lights on during PSG recording was reported.
Baseline and Day 14 (EODBT)
Change From Baseline in Percentage of N1, N2, N3 Stages, and REM Sleep Duration
Time Frame: Baseline and Day 14 (EODBT)
The change from baseline in duration of sleep time (percentage) of NREM sleep stages N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep was reported. Duration of sleep time was calculated from lights off to lights on during PSG recording.
Baseline and Day 14 (EODBT)
Change From Baseline in Latency to the First Period and Each Subsequent Period (Periods 2, 3, 4) of REM Sleep
Time Frame: Baseline and Day 14 (EODBT)
Latency to REM sleep (REML) for first period is the number of non-REM epochs in terms of minutes (stages N1 [light sleep], N2 [also fairly light, with sudden increases in brain wave frequency known as sleep spindles], N3 [slow wave or deep sleep]) from LPS to the first epoch of REM sleep. REML for second and subsequent REM periods is the number of non-REM and REM epochs in terms of minutes (stages N1, N2, N3, and REM) from LPS to the first epoch of the 2nd REM period, or subsequent REM period.
Baseline and Day 14 (EODBT)
Change From Baseline in REM Density
Time Frame: Baseline and Day 14 (EODBT)
REM density is the total number of REMs divided by the total duration of REM sleep in hours during time in bed (TIB).
Baseline and Day 14 (EODBT)
Change From Baseline in REM Activity (REMA)
Time Frame: Baseline and Day 14 (EODBT)
REMA is the total number of REMs during REM sleep, observed on the electrooculographic (EOG) channels of the PSG. The rapid eye movements must be at least 25 microvolts (uV) in amplitude.
Baseline and Day 14 (EODBT)
Change From Baseline in Insomnia Severity Index (ISI) Score
Time Frame: Baseline and Day 15
ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). The ISI possible total score range is from 0 to 28, categorized as follows: 0 to 7 = "no clinically significant insomnia", 8 to 14 = "subthreshold insomnia", 15 to 21 = "clinical insomnia (moderate severity)", and 22 to 28 = "clinical insomnia (severe)". Higher scores indicate severe insomnia.
Baseline and Day 15
Change From Baseline in Consensus Sleep Diary - Core (CSD-C) Parameters
Time Frame: Baseline and Day 15
The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including subjective sleep latency (sSL), subjective TST (sTST), subjective WASO (sWASO), and subjective sleep quality (sSQ), were derived from the CSD-C responses. Change from baseline in sSL, sTST and sWASO was reported in this outcome measure.
Baseline and Day 15
Change From Baseline in CSD-C Parameter: Subjective Sleep Quality (sSQ)
Time Frame: Baseline and Day 15
The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including sSL, sTST, sWASO, and sSQ, were derived from the CSD-C responses. Change from baseline in sSQ was reported in this outcome measure. Sleep quality is rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality.
Baseline and Day 15
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale
Time Frame: Baseline and Day 15
The severity of illness for each participant was rated using the CGI-S on a 7-point Likert scale with a total score range of 1-7 where a higher score represented a worse outcome. The participants were rated as: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill. In this study, the CGI-S was assessed based on the severity of insomnia disorder.
Baseline and Day 15
Mean Score of the Clinical Global Impression - Improvement (CGI-I) Scale
Time Frame: Day 15
The overall improvement in the participant's condition was assessed using CGI-I on a 7-point Likert scale with a total score range of 0-7 where a higher score represented a worse outcome. The participants were rated as: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. In this study, the CGI-I was assessed based on the improvement of insomnia disorder.
Day 15
Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score
Time Frame: Baseline and Day 15
The 17-item HAM-D was used to rate the severity of depression in participants who were already diagnosed as depressed. The 17-item HAM-D comprises individual ratings related to the following symptoms: Depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; Impaired ability to concentrate; Decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicate severe depression.
Baseline and Day 15
Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Score
Time Frame: Baseline and Day 15
PHQ-9 is a participant-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. Scoring is based on responses to specific questions, as follows: 0=not at all; 1=several days; 2=more than half the days; and 3=nearly every day. The PHQ-9 total score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score was categorized as follows: 1 to 4=minimal depression, 5 to 9=mild depression, 10 to 14=moderate depression, 15 to 19=moderately severe depression; and 20 to 27=severe depression. Higher scores indicate severe depression.
Baseline and Day 15
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From first dose of drug up to last follow-up visit (approximately 72 days)
An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs after the first administration of double-blind study drug or placebo. SAE is any untoward medical occurrence that at any dose results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect.
From first dose of drug up to last follow-up visit (approximately 72 days)
Number of Participants With Potentially Clinically Significant Vital Signs
Time Frame: Screening up to last follow-up visit (approximately 72 days)
Potentially clinically significant vital signs reported include supine and standing systolic blood pressure (SBP) [millimeters of mercury (mmHg)]: <90, >180, increase and decrease from baseline of >=30; Supine and standing diastolic blood pressure (DBP) (mmHg): Increase and decrease from baseline >=20; Standing heart rate (>120 beats per minute); Orthostatic SBP (>=20); Orthostatic DBP (>=10); Orthostatic hypotension (SBP >=20 and DBP >=10, SBP >=20 or DBP >=10).
Screening up to last follow-up visit (approximately 72 days)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Time Frame: Screening up to last follow-up visit (approximately 72 days)
Laboratory parameters include serum chemistry- Alanine aminotransferase: >3x upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase: >3x ULN; Bilirubin: >1.5x ULN, >2x ULN; Calcium: <2.0 millimoles per liter (mmol/L); Gamma Glutamyl Transferase [units per liter (U/L)]: >3xULN; Potassium: >5.4 mmol/L; Sodium: >150 mmol/L; Hematology- Hematocrit : Male <0.385 liter/liter (L/L) and Female <0.345 L/L and Male >0.55 L/L and Female >0.49 L/L; Hemoglobin: Male <115 grams/liter (g/L) and Female <100 g/L; Neutrophils: <1.5 10^9/L.
Screening up to last follow-up visit (approximately 72 days)
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
Time Frame: Screening up to last follow-up visit (approximately 72 days)
Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR, QRS, QT, and QTcF) as well as any rhythm abnormalities were recorded. Criteria for potentially clinically significant ECG abnormalities included QTcF interval (msec)- females: >450 to 480, male: >450 to 470, females: >480 to 500, male: >470 to 500 or >500.
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)
Time Frame: Screening up to last follow-up visit (approximately 72 days)
C-SSRS scale was used to monitor suicidality. The C-SSRS includes 'yes' or 'no' responses for 5 questions for assessment of suicidal ideation and behavior. Any suicidal behavior: when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.
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
Time Frame: Baseline, Days 18, 22, 28, 35 and 42
The PWC-20 was used to monitor for the presence of potential withdrawal symptoms following discontinuation of IP. It consists of a list of 20 symptoms (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue-lethargy-lack of energy, poor coordination, restlessness-agitation, diaphoresis, tremor-tremulousness, dizziness-lightheadedness, headaches, muscle aches or stiffness, weakness, increased acuity [sound, smell, touch, pain], paresthesia, difficulty concentrating and remembering, depersonalization-derealization) that were rated by the investigator on a scale of 0 (not present) to 3 (severe). The total score was derived as the sum of individual item scores, which ranges from 0 to 60. Higher scores indicate severe withdrawal. The total scores of PWC-20 were reported in this outcome measure.
Baseline, Days 18, 22, 28, 35 and 42

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 4, 2019

Primary Completion (Actual)

December 20, 2019

Study Completion (Actual)

January 17, 2020

Study Registration Dates

First Submitted

December 7, 2018

First Submitted That Met QC Criteria

December 7, 2018

First Posted (Actual)

December 11, 2018

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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