Trial Outcomes & Findings for Safety, Tolerability, PK Profile, and Symptom Response of a 7-Day Dosing With 25 mg or 50 mg Daily of REL-1017 in MDD (NCT NCT03051256)

Last Updated: 2023-11-01

Results Overview

Spontaneously reported or observed AEs will be recorded and reported throughout the study, and AEs will be elicited using a non-leading question at every visit from Screening through the Day 21 assessment. An AE was any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and may not necessarily have a causal relationship with the administered treatment. An AE could therefore be any unfavorable and unintended sign (including a clinically significant laboratory abnormality, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, regardless of relationship to the medicinal (investigational) product. During the study, an AE could also occur outside the time that the investigational product(s) was given (e.g., during the time from discontinuation of prohibited medications).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

62 participants

Primary outcome timeframe

21 days

Results posted on

2023-11-01

Participant Flow

Participant milestones

Participant milestones
Measure	REL-1017 25 mg Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Overall Study STARTED	19	21	22
Overall Study COMPLETED	19	21	21
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, PK Profile, and Symptom Response of a 7-Day Dosing With 25 mg or 50 mg Daily of REL-1017 in MDD

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 21 days

Population: Safety population: All randomized patients who received any study treatment (REL-1017 or placebo).

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=19 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=21 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=22 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Incidence of Treatment Emergent Adverse Events (AEs) [Safety and Tolerability] All-causality TEAEs	9 Participants	15 Participants	12 Participants
Incidence of Treatment Emergent Adverse Events (AEs) [Safety and Tolerability] All-causality SAEs	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Screening, Day -1, Day 1 hour 2, 8, Day 2 hour 2, 8, Day 3-7 hour 2, Day 8, Day 9, and Day 14

Population: Safety population: All randomized patients who received any study treatment (REL-1017 or placebo).

12-Lead ECGs will be performed and reported at Screening; at Check In (Day -1); Days 1 through 9; and at Day 14.

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=19 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=21 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=22 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
ECG Parameters [Safety] Day 9 (Discharge) · Abnormal (not clinically significant)	5 Participants	3 Participants	2 Participants
ECG Parameters [Safety] Day 9 (Discharge) · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Screening · Normal	14 Participants	19 Participants	16 Participants
ECG Parameters [Safety] Screening · Abnormal (not clinically significant)	5 Participants	2 Participants	6 Participants
ECG Parameters [Safety] Screening · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day -1 (Check-in) · Normal	17 Participants	19 Participants	20 Participants
ECG Parameters [Safety] Day -1 (Check-in) · Abnormal (not clinically significant)	2 Participants	2 Participants	2 Participants
ECG Parameters [Safety] Day -1 (Check-in) · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 1, 2 hrs post-dose · Normal	16 Participants	18 Participants	20 Participants
ECG Parameters [Safety] Day 1, 2 hrs post-dose · Abnormal (not clinically significant)	3 Participants	3 Participants	2 Participants
ECG Parameters [Safety] Day 1, 2 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 1, 8 hrs post-dose · Normal	15 Participants	18 Participants	20 Participants
ECG Parameters [Safety] Day 1, 8 hrs post-dose · Abnormal (not clinically significant)	4 Participants	3 Participants	2 Participants
ECG Parameters [Safety] Day 1, 8 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 2, 2 hrs post-dose · Normal	15 Participants	19 Participants	20 Participants
ECG Parameters [Safety] Day 2, 2 hrs post-dose · Abnormal (not clinically significant)	4 Participants	2 Participants	2 Participants
ECG Parameters [Safety] Day 2, 2 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 2, 8 hrs post-dose · Normal	15 Participants	19 Participants	19 Participants
ECG Parameters [Safety] Day 2, 8 hrs post-dose · Abnormal (not clinically significant)	4 Participants	2 Participants	2 Participants
ECG Parameters [Safety] Day 2, 8 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 3, 2 hrs post-dose · Normal	14 Participants	19 Participants	18 Participants
ECG Parameters [Safety] Day 3, 2 hrs post-dose · Abnormal (not clinically significant)	5 Participants	2 Participants	3 Participants
ECG Parameters [Safety] Day 3, 2 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 4, 2 hrs post-dose · Normal	15 Participants	19 Participants	19 Participants
ECG Parameters [Safety] Day 4, 2 hrs post-dose · Abnormal (not clinically significant)	4 Participants	2 Participants	2 Participants
ECG Parameters [Safety] Day 4, 2 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 5, 2 hrs post-dose · Normal	13 Participants	19 Participants	17 Participants
ECG Parameters [Safety] Day 5, 2 hrs post-dose · Abnormal (not clinically significant)	6 Participants	2 Participants	4 Participants
ECG Parameters [Safety] Day 5, 2 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 6, 2 hrs post-dose · Normal	15 Participants	18 Participants	18 Participants
ECG Parameters [Safety] Day 6, 2 hrs post-dose · Abnormal (not clinically significant)	4 Participants	3 Participants	3 Participants
ECG Parameters [Safety] Day 6, 2 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 7, 2 hrs post-dose · Normal	15 Participants	16 Participants	19 Participants
ECG Parameters [Safety] Day 7, 2 hrs post-dose · Abnormal (not clinically significant)	4 Participants	5 Participants	2 Participants
ECG Parameters [Safety] Day 7, 2 hrs post-dose · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 8 · Normal	15 Participants	17 Participants	19 Participants
ECG Parameters [Safety] Day 8 · Abnormal (not clinically significant)	4 Participants	4 Participants	2 Participants
ECG Parameters [Safety] Day 8 · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants
ECG Parameters [Safety] Day 9 (Discharge) · Normal	14 Participants	18 Participants	19 Participants
ECG Parameters [Safety] Day 14 · Normal	15 Participants	17 Participants	18 Participants
ECG Parameters [Safety] Day 14 · Abnormal (not clinically significant)	3 Participants	2 Participants	3 Participants
ECG Parameters [Safety] Day 14 · Abnormal (clinically significant)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 2, Day 8, Day 9 and Day 14

The C-SSRS will be administered and reported at Screening and Check In (Day -1); and at Days 1, 2, 8, 9 and 14. The C-SSRS is routinely used to quantify the severity of suicidal ideation and behavior. Both the ideation and behavior subscales are sensitive to change over time. The scale identifies behaviors that may be indicative of an individual's intent to commit suicide. This measure contains 6 "yes" or "no" questions in which respondents are asked to indicate whether they have experienced several thoughts or feelings relating to suicide over the past month. Each question addresses a different component of the respondent's suicide ideation severity: (1) Desire to be dead; (2) Suicidal thoughts; (3) Consideration of suicide methods; (4) Formed intent to commit suicide; (5) Completed suicide plan; and (6) Initiated suicide plan. A higher score indicates a higher intensity of suicidal ideation.

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=19 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=21 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=22 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Ideation (Any Score 1-5) : Day -1 (Check-in)	1 Participants	0 Participants	5 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Ideation (Any Score 1-5) : Day 1 (Baseline)	1 Participants	0 Participants	5 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Ideation (Any Score 1-5) : Day 2	0 Participants	0 Participants	0 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Ideation (Any Score 1-5) : Day 8	0 Participants	1 Participants	1 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Ideation (Any Score 1-5) : Day 9 (Discharge)	0 Participants	1 Participants	1 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Ideation (Any Score 1-5) : Day 14	1 Participants	1 Participants	1 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Behavior (any) : Day -1 (Check-in)	0 Participants	0 Participants	0 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Behavior (any) : Day 1 (Baseline)	0 Participants	0 Participants	0 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Behavior (any) : Day 2	0 Participants	0 Participants	0 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Behavior (any) : Day 8	0 Participants	0 Participants	0 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Behavior (any) : Day 9 (Discharge)	0 Participants	0 Participants	0 Participants
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Participants with Suicidal Behavior (any) : Day 14	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Change from Baseline to Day 7

Population: ITT Population

Montgomery-Asberg Depression Scale (MADRS) will be administered and reported on Days 4, 7, and 14. The MADRS questionnaire includes questions on the following symptoms: (1) Apparent sadness; (2) Reported sadness; (3) Inner tension; (4) Reduced sleep; (5) Reduced appetite; (6) Concentration difficulties; (7) Lassitude; (8) Inability to feel; (9) Pessimistic thoughts; (10) Suicidal thoughts. A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. In Study REL-1017-202, the MADRS was administered using the Structured Interview Guide for the MADRS (SIGMA). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=19 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=21 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=21 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Montgomery-Asberg Depression Scale (MADRS)	-17.4 score on a scale Standard Error 2.5	-15.9 score on a scale Standard Error 2.4	-8.7 score on a scale Standard Error 2.3

SECONDARY outcome

Timeframe: Change from Baseline to Day 14

Population: ITT Population

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=16 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=18 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=20 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Montgomery-Asberg Depression Scale (MADRS)	-16.8 score on a scale Standard Error 2.7	-17.8 score on a scale Standard Error 2.6	-7.4 score on a scale Standard Error 2.4

SECONDARY outcome

Timeframe: Change from Baseline to Day 7

Population: ITT Population

Symptoms of Depression Questionnaire (SDQ) will be administered and reported on Days 4, 7, and 14. The SDQ is a 44-item, self-report scale designed to measure the severity of symptoms across several subtypes of depression. The SDQ was developed to more fully capture the heterogeneity of symptom presentations of depressive disorders than current, widely used scales for MDD. The SDQ includes items that inquire about an extensive number of depressive symptoms beyond the ones included in other commonly used scales. The 44 SDQ items are rated on a 6-point scale. The total score is the sum of 44 items and can range from 44 to 264. A negative change from baseline indicates improvement. 1 = Better than Normal; 2= Normal; 3= Minimally Sad; 4= Moderately Sad; 5= Markedly Sad; 6= Extremely Sad

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=19 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=21 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=21 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Symptoms of Depression Questionnaire (SDQ)	-52.4 score on a scale Standard Error 7.1	-52.9 score on a scale Standard Error 6.6	-37.9 score on a scale Standard Error 6.4

SECONDARY outcome

Timeframe: Change from Baseline to Day 14

Population: ITT Population

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=16 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=18 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=20 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Symptoms of Depression Questionnaire (SDQ)	-55.0 score on a scale Standard Error 6.4	-58.6 score on a scale Standard Error 6.0	-31.8 score on a scale Standard Error 5.6

SECONDARY outcome

Timeframe: Change from Baseline to Day 7

Population: ITT Population

Clinical Global Impressions of Severity (CGI-S) will be administered and reported on Days 4, 7, and 14. The CGI-S is a standard method used in clinical studies to quantify and track patient progress and treatment response over time. The scale is composed of 7 ratings: 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 patients. The score ranges from 1 to 7, and a lower CGI-S score indicates lower levels of depression.

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=19 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=21 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=21 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Clinical Global Impressions of Severity (CGI-S)	-1.7 score on a scale Standard Error 0.3	-1.7 score on a scale Standard Error 0.3	-0.8 score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Change from Baseline to Day 14

Population: ITT Population

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=16 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=18 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=20 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Clinical Global Impressions of Severity (CGI-S)	-1.6 score on a scale Standard Error 0.3	-2.0 score on a scale Standard Error 0.3	-0.7 score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Change from Baseline to Day 7

Clinical Global Impressions of Improvement (CGI-I) will be administered and reported at Days 4, 7 and 14. The CGI-I is a standard method used in clinical studies to quantify and track patient change over time. The scale is composed of 7 ratings: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; and 7 = very much worse. The score ranges from 1 to 7, and a lower CGI-I score indicates greater improvement in symptoms.

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=19 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=21 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=21 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Clinical Global Impressions of Improvement (CGI-I)	2.4 score on a scale Standard Error 0.2	2.3 score on a scale Standard Error 0.2	3.2 score on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Change from Baseline to Day 14

Outcome measures

Outcome measures
Measure	REL-1017 25 mg n=16 Participants Loading dose of REL-1017 75 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 25 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	REL-1017 50 mg n=18 Participants Loading dose of REL-1017 100 mg of powder in 100 mL of cranberry juice on Day 1, Maintenance dose of REL-1017 50 mg of powder in 100 mL cranberry juice daily on Days 2-7. REL-1017: REL-1017 administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.	Placebo n=20 Participants 100 mL cranberry juice was administered as a single oral dose daily for 7 days. Placebo: Placebo was administered as an oral solution. Patients continued to take the first line stable dose of antidepressant medication.
Clinical Global Impressions of Improvement (CGI-I)	2.6 score on a scale Standard Error 0.3	2.3 score on a scale Standard Error 0.3	3.3 score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Day 1 (hour -1, 1, 2, 4, 6, 8, 12, and 24)

Population: Pharmacokinetic population: All patients who received REL-1017, with at least 1 post-dose blood draw to determine plasma concentration of d-methadone.