Trial Outcomes & Findings for Safety of REL-1017 for Major Depressive Disorder (NCT NCT04855760)

NCT ID: NCT04855760

Last Updated: 2025-02-11

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 627 participants
• Primary outcome timeframe: 52 weeks
• Results posted on: 2025-02-11

Participant Flow

Participant milestones

Measure	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. REL-1017: REL-1017 tablet
Overall Study STARTED	627
Overall Study Dosed	624
Overall Study COMPLETED	182
Overall Study NOT COMPLETED	445

Reasons for withdrawal

Measure	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. REL-1017: REL-1017 tablet
Overall Study Adverse Event	21
Overall Study Withdrawal by Subject	116
Overall Study Lack of Efficacy	21
Overall Study Lost to Follow-up	49
Overall Study Protocol Violation	2
Overall Study Physician Decision	5
Overall Study Pregnancy	1
Overall Study Non-Compliance with Study Drug	11
Overall Study Non-Compliance with Study Schedule	4
Overall Study Study Completed by Sponsor	202
Overall Study Other	13

Baseline Characteristics

Safety of REL-1017 for Major Depressive Disorder

Baseline characteristics by cohort

Measure	REL-1017 n=624 Participants Total participants in Open Label Study, including: Roll-over participants, 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 receiving REL1017 as either monotherapy or as adjunctive therapy. REL-1017: REL-1017 tablet
Age, Continuous	42.9 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	433 Participants n=5 Participants
Sex: Female, Male Male	191 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	162 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	442 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	24 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	95 Participants n=5 Participants
Race (NIH/OMB) White	474 Participants n=5 Participants
Race (NIH/OMB) More than one race	16 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 52 weeks

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

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

Outcome measures

Measure	REL-1017 n=624 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs)	350 participants

SECONDARY outcome

Timeframe: 3 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=534 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3	4.11 ms Standard Deviation 14.54

SECONDARY outcome

Timeframe: 6 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=435 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6	2.70 ms Standard Deviation 15.26

SECONDARY outcome

Timeframe: 12 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=198 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12	2.59 ms Standard Deviation 13.77

SECONDARY outcome

Timeframe: 3 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=505 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Diastolic Blood Pressure From Baseline to Month 3	0.5 mmHg Standard Deviation 7.3

SECONDARY outcome

Timeframe: 12 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=186 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Diastolic Blood Pressure From Baseline to Month 12	-0.2 mmHg Standard Deviation 8.4

SECONDARY outcome

Timeframe: 3 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=505 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Systolic Blood Pressure From Baseline to Month 3	0.4 mmHg Standard Deviation 9.9

SECONDARY outcome

Timeframe: 12 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=186 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Systolic Blood Pressure From Baseline to Month 12	0.0 mmHg Standard Deviation 10.9

SECONDARY outcome

Timeframe: 3 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=505 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Heart Rate From Baseline to Month 3	0.8 beats/min Standard Deviation 9.2

SECONDARY outcome

Timeframe: 12 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=186 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Heart Rate From Baseline to Month 12	-0.1 beats/min Standard Deviation 9.6

SECONDARY outcome

Timeframe: 3 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=545 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Weight From Baseline to Month 3	0.32 kg Standard Deviation 4.45

SECONDARY outcome

Timeframe: 12 Month

Population: Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and 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.

Outcome measures

Measure	REL-1017 n=197 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in Weight From Baseline to Month 12	0.33 kg Standard Deviation 5.56

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 Month

Population: Full Analysis Set (FAS) at Month 3: All participants who received at least 1 dose of study drug and had at least one post-Baseline efficacy assessment, irrespective of any deviation from the protocol or premature discontinuation at 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.

Outcome measures

Measure	REL-1017 n=536 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in the MADRS10 Total Score From Baseline to Month 3	-20.1 units on a scale Standard Deviation 10.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 Month

Population: Full Analysis Set (FAS) at Month 12: All participants who received at least 1 dose of study drug and had at least one post-Baseline efficacy assessment, irrespective of any deviation from the protocol or premature discontinuation at 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.

Outcome measures

Measure	REL-1017 n=199 Participants Total participants in Open Label Study REL-1017: REL-1017 tablet
Change in the MADRS10 Total Score From Baseline to Month 12	-21.6 units on a scale Standard Deviation 10.4

Adverse Events

REL-1017

Serious events: 8 serious events

Other events: 142 other events

Deaths: 0 deaths

Serious adverse events

Measure	REL-1017 n=624 participants at risk Total participants in Open Label Study REL-1017: REL-1017 tablet
Cardiac disorders Coronary artery disease	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Cardiac disorders Tachycardia	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Psychiatric disorders Alcohol abuse	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Psychiatric disorders Anxiety	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Immune system disorders Anaphylactic reaction	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Infections and infestations Bacteraemia	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Infections and infestations Pyelonephritis	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Metabolism and nutrition disorders Hyperglycaemia	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Nervous system disorders Hyperreflexia	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Nervous system disorders Tremor	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.
Infections and infestations Sepsis	0.16% 1/624 • Number of events 1 • 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. A TEAE is defined as an 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.

Other adverse events

Measure	REL-1017 n=624 participants at risk Total participants in Open Label Study REL-1017: REL-1017 tablet
Infections and infestations COVID-19	9.6% 60/624 • Number of events 62 • 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. A TEAE is defined as an 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.
Nervous system disorders Headache	9.8% 61/624 • Number of events 77 • 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. A TEAE is defined as an 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.
Infections and infestations Upper respiratory tract infections	8.5% 53/624 • Number of events 67 • 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. A TEAE is defined as an 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.

Additional Information

Marco Pappagallo, MD

Relmada Therapeutics

Phone: 786-638-7384

Email: info@relmada.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place