E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056393 |
E.1.2 | Term | Postpartum depression |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine if treatment with SAGE-217 reduces depressive symptoms in adults with severe postpartum depression (PPD) compared to placebo |
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E.2.2 | Secondary objectives of the trial |
To determine if treatment with SAGE-217 reduces anxiety symptoms compared to placebo To assess self-report of depressive symptoms To evaluate the safety and tolerability of SAGE-217
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Participant has ceased lactating or agrees not to provide breastmilk to her infant(s) from just prior to receiving the investigational product (IP) on Day 1 until 7 days after the last dose of IP. -Participant has had a major depressive episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, as diagnosed by Structured Clinical Interview for Diagnostic and DSM-5 Clinical Trial Version (SCID-5-CT). -Participant is ≤6 months postpartum
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E.4 | Principal exclusion criteria |
-Participant is at significant risk of suicide or has attempted suicide associated with the current episode of PPD. -Participant has active psychosis per investigator assessment. -Participant has a medical history of nonfebrile seizures. -Participant has a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder. -Participant has a history of sleep apnea.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) total score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Change From Baseline in the 17-item HAM-D Total Score [ Time Frame: Baseline and Days 3, 28 and 45 ] The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.
•Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score [ Time Frame: Baseline and Day 15 ] The CGI-S is a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. A participant is assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants.
•Percentage of Participants With HAM-D Response [ Time Frame: Baseline and Days 15 and 45 ] HAM-D response is defined as a ≥50% reduction in HAM-D score from baseline.
•Percentage of Participants With HAM-D Remission [ Time Frame: Days 15 and 45 ] HAM-D remission is defined as HAM-D total score ≤7.
•Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Day 15 ] CGI-I response is defined as having a CGI-I score of "very much improved" or "much improved." The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. Response choices include 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse.
•Change From Baseline in Hamilton Rating Scale for Anxiety (HAM-A) Total Score [ Time Frame: Baseline and Day 15 ] The 14-item HAM-A is comprised of a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A total score will be calculated as the sum of the 14 individual item scores. The scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56.
•Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Day 15 ] The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item is rated on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression.
•Change From Baseline in HAM-D Subscale [ Time Frame: Baseline and Day 15 ] The 17-item HAM-D is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. HAM-D subscale scores will be calculated as the sum of the items comprising each subscale. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe.
•Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score [ Time Frame: Baseline and up to Day 45 ] The EPDS is a self-rated depressive symptom severity scale specific to the perinatal period which consists of 10 individual items. Each item is rated on a 4-point scale ranging from 0 to 3 points. The EPDS total score is calculated as the sum of the 10 individual item scores, ranging from 0 points to 30 points with a higher score indicating more depression.
•Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score [ Time Frame: Baseline and up to Day 45 ] The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score will be calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression.
•Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Up to Day 45 ]
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See the timepoints of evaluation per endpoint above |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 24 |