Major Depressive Disorder
Conditions
Keywords
REL-1017
Brief 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.
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.
Interventions
DRUGREL-1017
REL-1017 tablet
Sponsors
Relmada Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs) | 52 weeks | Subjects with at least one Treatment Emergent Adverse Events (TEAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3 | 3 Month | 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. |
| Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6 | 6 Month | 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. |
| Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12 | 12 Month | 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. |
| Change in Diastolic Blood Pressure From Baseline to Month 3 | 3 Month | 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. |
| Change in Diastolic Blood Pressure From Baseline to Month 12 | 12 Month | 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. |
| Change in Systolic Blood Pressure From Baseline to Month 3 | 3 Month | 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. |
| Change in Weight From Baseline to Month 3 | 3 Month | Overall Safety of REL-1017 as measured by Weight From Baseline to Month 3. A negative change from baseline indicates a reduction in Weight. |
| Change in Weight From Baseline to Month 12 | 12 Month | Overall Safety of REL-1017 as measured by Weight From Baseline to Month 12. A negative change from baseline indicates a reduction in Weight. |
| Change in Systolic Blood Pressure From Baseline to Month 12 | 12 Month | 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. |
| Change in Heart Rate From Baseline to Month 3 | 3 Month | 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. |
| Change in Heart Rate From Baseline to Month 12 | 12 Month | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in the MADRS10 Total Score From Baseline to Month 3 | 3 Month | 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. |
| Change in the MADRS10 Total Score From Baseline to Month 12 | 12 Month | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| REL-1017 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 | 624 |
| Total | 624 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 21 |
| Overall Study | Lack of Efficacy | 21 |
| Overall Study | Lost to Follow-up | 49 |
| Overall Study | Non-Compliance with Study Drug | 11 |
| Overall Study | Non-Compliance with Study Schedule | 4 |
| Overall Study | Other | 13 |
| Overall Study | Physician Decision | 5 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Study Completed by Sponsor | 202 |
| Overall Study | Withdrawal by Subject | 116 |
Baseline characteristics
| Characteristic | REL-1017 |
|---|---|
| Age, Continuous | 42.9 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 162 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 442 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 24 Participants |
| Race (NIH/OMB) Black or African American | 95 Participants |
| Race (NIH/OMB) More than one race | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 474 Participants |
| Sex: Female, Male Female | 433 Participants |
| Sex: Female, Male Male | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 624 |
| other Total, other adverse events | 142 / 624 |
| serious Total, serious adverse events | 8 / 624 |
Outcome results
Primary
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
Population: Safety Analysis Set: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REL-1017 | Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs) | 350 participants |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Diastolic Blood Pressure From Baseline to Month 12 | -0.2 mmHg | Standard Deviation 8.4 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Diastolic Blood Pressure From Baseline to Month 3 | 0.5 mmHg | Standard Deviation 7.3 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Heart Rate From Baseline to Month 12 | -0.1 beats/min | Standard Deviation 9.6 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Heart Rate From Baseline to Month 3 | 0.8 beats/min | Standard Deviation 9.2 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Systolic Blood Pressure From Baseline to Month 12 | 0.0 mmHg | Standard Deviation 10.9 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Systolic Blood Pressure From Baseline to Month 3 | 0.4 mmHg | Standard Deviation 9.9 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12 | 2.59 ms | Standard Deviation 13.77 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3 | 4.11 ms | Standard Deviation 14.54 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6 | 2.70 ms | Standard Deviation 15.26 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Weight From Baseline to Month 12 | 0.33 kg | Standard Deviation 5.56 |
Secondary
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in Weight From Baseline to Month 3 | 0.32 kg | Standard Deviation 4.45 |
Other Pre-specified
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in the MADRS10 Total Score From Baseline to Month 12 | -21.6 units on a scale | Standard Deviation 10.4 |
Other Pre-specified
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REL-1017 | Change in the MADRS10 Total Score From Baseline to Month 3 | -20.1 units on a scale | Standard Deviation 10.7 |