CClinicalTrials.gg
Sign In
CompletedNCT04855760RELIANCE-OLSUpdated Feb 11, 2025Results posted

Safety of REL-1017 for Major Depressive Disorder

A Phase 3 interventional study of REL-1017 in Major Depressive Disorder, sponsored by Relmada Therapeutics, Inc.. Completed at 9 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-02-11.

Sponsored by Relmada Therapeutics, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
627
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This was a 1-year, multicenter, open-label, long-term study to assess the safety of REL-1017 once daily (QD) as monotherapy or as adjunctive treatment of Major Depressive Disorder. Adjunctive study participants continued to take their current antidepressant therapy in addition to the study drug for the duration of the treatment period.

Read the detailed description

This was a multicenter, open-label, long-term study of REL-1017 to evaluate the long-term safety and long-term durability of response in patients with MDD. Patients who completed previous randomized, double-blind Phase 3 trials (NCT04688164, NCT04855747, NCT05081167) of REL-1017 as adjunctive therapy or monotherapy for MDD were asked to continue treatment with REL-1017 25 mg daily for up to 1 year. De novo patients who satisfied inclusion/exclusion criteria also were enrolled and received a 75 mg loading dose of REL-1017 on Day 1 followed by a maintenance dose of 25 mg REL-1017 daily for the remainder of the study (Days 2-365). When REL-1017 was administered as adjunctive treatment, patients continued to use a stable dosage of their concomitant antidepressants.

02

Conditions studied

  • Major Depressive Disorder

Keywords

  • REL-1017
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Adults 18 to 65 years, inclusive.
  • Diagnosed with Major Depressive Disorder (MDD) based on Structured Clinical Interview for DSM-5 (SCID-5) for MDD.
  • Current major depressive episode.

Exclusion criteria

Exclusion Criteria:

  • Any current and primary psychiatric disorder other than Major Depressive Disorder.
  • History of bipolar I and II disorder, psychosis, and/or mania.
  • Acute or chronic condition that, in the Investigator's opinion, would limit the subject's ability to complete or participate in this clinical study.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
627 participants (actual)

Study arms

  • Experimental
    REL-1017

    Roll-over participants received 25 mg REL-1017 (one 25 mg REL-1017 tablet), orally, per day, either as a monotherapy or in addition to their ongoing antidepressant (ADT), rolling over from the monotherapy study REL-1017-303 or the adjunctive therapy studies REL-1017-301 and REL-1017-302, respectively. De Novo participants received a 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) on Day-1 of the 365-day treatment period. From Day-2 to Day-365, participants received 25 mg REL-1017 either as monotherapy or as adjunctive therapy.

    Drug: REL-1017

Interventions

  • DrugREL-1017

    REL-1017 tablet

    Also known as: Esmethadone HCl

05

What researchers measure

Primary outcomes

  1. Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)

    Subjects with at least one Treatment Emergent Adverse Events (TEAEs)

    Time frame: 52 weeks

Secondary outcomes

  1. Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3

    Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 3. A negative change from baseline indicates shortening of the QTcF.

    Time frame: 3 Month

  2. Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6

    Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 6. A negative change from baseline indicates shortening of the QTcF.

    Time frame: 6 Month

  3. Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12

    Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 12. A negative change from baseline indicates shortening of the QTcF.

    Time frame: 12 Month

  4. Change in Diastolic Blood Pressure From Baseline to Month 3

    Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Diastolic Blood Pressure.

    Time frame: 3 Month

  5. Change in Diastolic Blood Pressure From Baseline to Month 12

    Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Diastolic Blood Pressure.

    Time frame: 12 Month

  6. Change in Systolic Blood Pressure From Baseline to Month 3

    Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Systolic Blood Pressure.

    Time frame: 3 Month

  7. Change in Systolic Blood Pressure From Baseline to Month 12

    Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Systolic Blood Pressure.

    Time frame: 12 Month

  8. Change in Heart Rate From Baseline to Month 3

    Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Heart Rate.

    Time frame: 3 Month

  9. Change in Heart Rate From Baseline to Month 12

    Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Heart Rate.

    Time frame: 12 Month

  10. Change in Weight From Baseline to Month 3

    Overall Safety of REL-1017 as measured by Weight From Baseline to Month 3. A negative change from baseline indicates a reduction in Weight.

    Time frame: 3 Month

  11. Change in Weight From Baseline to Month 12

    Overall Safety of REL-1017 as measured by Weight From Baseline to Month 12. A negative change from baseline indicates a reduction in Weight.

    Time frame: 12 Month

Other outcomes

  1. Change in the MADRS10 Total Score From Baseline to Month 3

    Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) 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. A negative change from baseline indicates improvement.

    Time frame: 3 Month

  2. Change in the MADRS10 Total Score From Baseline to Month 12

    Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) 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. A negative change from baseline indicates improvement.

    Time frame: 12 Month

06

Results

Posted Aug 9, 2024

Participant flow

Participant flow — Overall Study
MilestoneREL-1017
Started627
Dosed624
Completed182
Not completed445
Withdrew: Adverse event21
Withdrew: Withdrawal by subject116
Withdrew: Lack of efficacy21
Withdrew: Lost to follow-up49
Withdrew: Protocol violation2
Withdrew: Physician decision5
Withdrew: Pregnancy1
Withdrew: Non-compliance with study drug11
Withdrew: Non-compliance with study schedule4
Withdrew: Study completed by sponsor202
Withdrew: Other13

Outcome measures

PrimarySafety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)

Subjects with at least one Treatment Emergent Adverse Events (TEAEs)

Time frame:
52 weeks
Reported as:
Number · participants
Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)
participantsREL-1017
Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)350
SecondaryChange in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3

Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 3. A negative change from baseline indicates shortening of the QTcF.

Time frame:
3 Month
Reported as:
Mean · ms
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3
msREL-1017
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 34.11 ± 14.54
SecondaryChange in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6

Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 6. A negative change from baseline indicates shortening of the QTcF.

Time frame:
6 Month
Reported as:
Mean · ms
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6
msREL-1017
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 62.70 ± 15.26
SecondaryChange in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12

Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 12. A negative change from baseline indicates shortening of the QTcF.

Time frame:
12 Month
Reported as:
Mean · ms
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12
msREL-1017
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 122.59 ± 13.77
SecondaryChange in Diastolic Blood Pressure From Baseline to Month 3

Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Diastolic Blood Pressure.

Time frame:
3 Month
Reported as:
Mean · mmHg
Change in Diastolic Blood Pressure From Baseline to Month 3
mmHgREL-1017
Change in Diastolic Blood Pressure From Baseline to Month 30.5 ± 7.3
SecondaryChange in Diastolic Blood Pressure From Baseline to Month 12

Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Diastolic Blood Pressure.

Time frame:
12 Month
Reported as:
Mean · mmHg
Change in Diastolic Blood Pressure From Baseline to Month 12
mmHgREL-1017
Change in Diastolic Blood Pressure From Baseline to Month 12-0.2 ± 8.4
SecondaryChange in Systolic Blood Pressure From Baseline to Month 3

Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Systolic Blood Pressure.

Time frame:
3 Month
Reported as:
Mean · mmHg
Change in Systolic Blood Pressure From Baseline to Month 3
mmHgREL-1017
Change in Systolic Blood Pressure From Baseline to Month 30.4 ± 9.9
SecondaryChange in Systolic Blood Pressure From Baseline to Month 12

Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Systolic Blood Pressure.

Time frame:
12 Month
Reported as:
Mean · mmHg
Change in Systolic Blood Pressure From Baseline to Month 12
mmHgREL-1017
Change in Systolic Blood Pressure From Baseline to Month 120.0 ± 10.9
SecondaryChange in Heart Rate From Baseline to Month 3

Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Heart Rate.

Time frame:
3 Month
Reported as:
Mean · beats/min
Change in Heart Rate From Baseline to Month 3
beats/minREL-1017
Change in Heart Rate From Baseline to Month 30.8 ± 9.2
SecondaryChange in Heart Rate From Baseline to Month 12

Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Heart Rate.

Time frame:
12 Month
Reported as:
Mean · beats/min
Change in Heart Rate From Baseline to Month 12
beats/minREL-1017
Change in Heart Rate From Baseline to Month 12-0.1 ± 9.6
SecondaryChange in Weight From Baseline to Month 3

Overall Safety of REL-1017 as measured by Weight From Baseline to Month 3. A negative change from baseline indicates a reduction in Weight.

Time frame:
3 Month
Reported as:
Mean · kg
Change in Weight From Baseline to Month 3
kgREL-1017
Change in Weight From Baseline to Month 30.32 ± 4.45
SecondaryChange in Weight From Baseline to Month 12

Overall Safety of REL-1017 as measured by Weight From Baseline to Month 12. A negative change from baseline indicates a reduction in Weight.

Time frame:
12 Month
Reported as:
Mean · kg
Change in Weight From Baseline to Month 12
kgREL-1017
Change in Weight From Baseline to Month 120.33 ± 5.56
Other pre-specifiedChange in the MADRS10 Total Score From Baseline to Month 3

Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) 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. A negative change from baseline indicates improvement.

Time frame:
3 Month
Reported as:
Mean · units on a scale
Change in the MADRS10 Total Score From Baseline to Month 3
units on a scaleREL-1017
Change in the MADRS10 Total Score From Baseline to Month 3-20.1 ± 10.7
Other pre-specifiedChange in the MADRS10 Total Score From Baseline to Month 12

Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) 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. A negative change from baseline indicates improvement.

Time frame:
12 Month
Reported as:
Mean · units on a scale
Change in the MADRS10 Total Score From Baseline to Month 12
units on a scaleREL-1017
Change in the MADRS10 Total Score From Baseline to Month 12-21.6 ± 10.4

Adverse events

Collected over A Treatment Emergent Adverse Event (TEAE) is defined as an Adverse Event (AE) that starts or worsens at any time after initiation of study drug collected up to 1 month post treatment (Day 395) as collected in the Safety Analysis Set.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
REL-10170/624 (0%)8/624 (1.3%)142/624 (22.8%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventREL-1017
Coronary artery diseaseCardiac disorders1/624
TachycardiaCardiac disorders1/624
Alcohol abusePsychiatric disorders1/624
AnxietyPsychiatric disorders1/624
Anaphylactic reactionImmune system disorders1/624
BacteraemiaInfections and infestations1/624
PyelonephritisInfections and infestations1/624
HyperglycaemiaMetabolism and nutrition disorders1/624
HyperreflexiaNervous system disorders1/624
TremorNervous system disorders1/624
Most frequent other events
Most frequent other events
EventREL-1017
HeadacheNervous system disorders61/624
COVID-19Infections and infestations60/624
Upper respiratory tract infectionsInfections and infestations53/624

Baseline characteristics

Safety Analysis Set: All participants who received at least 1 dose of study drug.

Age, Continuous
Age, Continuous(years)REL-1017
Mean42.9 ± 13.6
Sex: Female, Male
Sex: Female, Male(Participants)REL-1017
Female433
Male191
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)REL-1017
Hispanic or Latino162
Not Hispanic or Latino442
Unknown or Not Reported20
Race (NIH/OMB)
Race (NIH/OMB)(Participants)REL-1017
American Indian or Alaska Native1
Asian24
Native Hawaiian or Other Pacific Islander1
Black or African American95
White474
More than one race16
Unknown or Not Reported13
07

Study locations

9 sites
  • Relmada Site
    Miami, Florida 33015, United States
  • Relmada Site
    Miami, Florida 33175, United States
  • Relmada Site
    Orlando, Florida 32801, United States
  • Relmada Site
    Palm Bay, Florida 32905, United States
  • Relmada Site
    Chicago, Illinois 60634, United States
  • Relmada Site
    Chicago, Illinois 60640, United States
  • Relmada Site
    Boston, Massachusetts 02116, United States
  • Relmada Site
    Watertown, Massachusetts 02472, United States
  • Relmada Site
    Staten Island, New York 10312, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Mar 4, 2022

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04855760
Lead sponsor
Relmada Therapeutics, Inc.
Responsible party
Sponsor
First posted
Apr 22, 2021
Start date
Apr 1, 2021
Primary completion
Jul 27, 2023
Completion
Jul 27, 2023
Results posted
Aug 9, 2024
Last update
Feb 11, 2025

Study contacts

Marco Pappagallo, MD
study director · Relmada Therapeutics

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Depressive Disorder→

Other studies from this sponsor

Relmada Therapeutics, Inc.

Start the discussion