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NCT03051256

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

Completed Phase 2 Results posted Last updated 1 November 2023
What this trial tests

Phase 2 trial testing REL-1017 in Depressive Disorder, Major in 62 participants. Completed in 30 September 2019.

Timeline
11 May 2018
Primary endpoint
30 July 2019
30 September 2019

Quick facts

Lead sponsorRelmada Therapeutics, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment62
Start date11 May 2018
Primary completion30 July 2019
Estimated completion30 September 2019
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Relmada Therapeutics, Inc. — full company profile →

Who can join

Adults 18 to 65, any sex, with Depressive Disorder, Major or Depressive Disorder, Treatment-Resistant. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Incidence of Treatment Emergent Adverse Events (AEs) [Safety and Tolerability] Primary · 21 days

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

All-causality TEAEs
GroupValue95% CI
REL-1017 25 mg9
REL-1017 50 mg15
Placebo12
All-causality SAEs
GroupValue95% CI
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
ECG Parameters [Safety] Secondary · 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

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

Screening
GroupValue95% CI
REL-1017 25 mg14
REL-1017 50 mg19
Placebo16
REL-1017 25 mg5
REL-1017 50 mg2
Placebo6
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Day -1 (Check-in)
GroupValue95% CI
REL-1017 25 mg17
REL-1017 50 mg19
Placebo20
REL-1017 25 mg2
REL-1017 50 mg2
Placebo2
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Day 1, 2 hrs post-dose
GroupValue95% CI
REL-1017 25 mg16
REL-1017 50 mg18
Placebo20
REL-1017 25 mg3
REL-1017 50 mg3
Placebo2
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Day 1, 8 hrs post-dose
GroupValue95% CI
REL-1017 25 mg15
REL-1017 50 mg18
Placebo20
REL-1017 25 mg4
REL-1017 50 mg3
Placebo2
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Day 2, 2 hrs post-dose
GroupValue95% CI
REL-1017 25 mg15
REL-1017 50 mg19
Placebo20
REL-1017 25 mg4
REL-1017 50 mg2
Placebo2
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Day 2, 8 hrs post-dose
GroupValue95% CI
REL-1017 25 mg15
REL-1017 50 mg19
Placebo19
REL-1017 25 mg4
REL-1017 50 mg2
Placebo2
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Day 3, 2 hrs post-dose
GroupValue95% CI
REL-1017 25 mg14
REL-1017 50 mg19
Placebo18
REL-1017 25 mg5
REL-1017 50 mg2
Placebo3
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Day 4, 2 hrs post-dose
GroupValue95% CI
REL-1017 25 mg15
REL-1017 50 mg19
Placebo19
REL-1017 25 mg4
REL-1017 50 mg2
Placebo2
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Columbia Suicide Severity Rating Scale (C-SSRS) [Safety and Tolerability] Secondary · 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 diffe

Participants with Suicidal Ideation (Any Score 1-5) : Day -1 (Check-in)
GroupValue95% CI
REL-1017 25 mg1
REL-1017 50 mg0
Placebo5
Participants with Suicidal Ideation (Any Score 1-5) : Day 1 (Baseline)
GroupValue95% CI
REL-1017 25 mg1
REL-1017 50 mg0
Placebo5
Participants with Suicidal Ideation (Any Score 1-5) : Day 2
GroupValue95% CI
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Participants with Suicidal Ideation (Any Score 1-5) : Day 8
GroupValue95% CI
REL-1017 25 mg0
REL-1017 50 mg1
Placebo1
Participants with Suicidal Ideation (Any Score 1-5) : Day 9 (Discharge)
GroupValue95% CI
REL-1017 25 mg0
REL-1017 50 mg1
Placebo1
Participants with Suicidal Ideation (Any Score 1-5) : Day 14
GroupValue95% CI
REL-1017 25 mg1
REL-1017 50 mg1
Placebo1
Participants with Suicidal Behavior (any) : Day -1 (Check-in)
GroupValue95% CI
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Participants with Suicidal Behavior (any) : Day 1 (Baseline)
GroupValue95% CI
REL-1017 25 mg0
REL-1017 50 mg0
Placebo0
Montgomery-Asberg Depression Scale (MADRS) Secondary · Change from Baseline to Day 7

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

GroupValue95% CI
REL-1017 25 mg-17.4± 2.5
REL-1017 50 mg-15.9± 2.4
Placebo-8.7± 2.3
Montgomery-Asberg Depression Scale (MADRS) Secondary · Change from Baseline to Day 14

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

GroupValue95% CI
REL-1017 25 mg-16.8± 2.7
REL-1017 50 mg-17.8± 2.6
Placebo-7.4± 2.4
Symptoms of Depression Questionnaire (SDQ) Secondary · Change from Baseline to Day 7

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 it

GroupValue95% CI
REL-1017 25 mg-52.4± 7.1
REL-1017 50 mg-52.9± 6.6
Placebo-37.9± 6.4
Symptoms of Depression Questionnaire (SDQ) Secondary · Change from Baseline to Day 14

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 it

GroupValue95% CI
REL-1017 25 mg-55.0± 6.4
REL-1017 50 mg-58.6± 6.0
Placebo-31.8± 5.6
Clinical Global Impressions of Severity (CGI-S) Secondary · Change from Baseline to Day 7

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.

GroupValue95% CI
REL-1017 25 mg-1.7± 0.3
REL-1017 50 mg-1.7± 0.3
Placebo-0.8± 0.3
Clinical Global Impressions of Severity (CGI-S) Secondary · Change from Baseline to Day 14

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.

GroupValue95% CI
REL-1017 25 mg-1.6± 0.3
REL-1017 50 mg-2.0± 0.3
Placebo-0.7± 0.3
Clinical Global Impressions of Improvement (CGI-I) Secondary · 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.

GroupValue95% CI
REL-1017 25 mg2.4± 0.2
REL-1017 50 mg2.3± 0.2
Placebo3.2± 0.2
Clinical Global Impressions of Improvement (CGI-I) Secondary · Change from Baseline to Day 14

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.

GroupValue95% CI
REL-1017 25 mg2.6± 0.3
REL-1017 50 mg2.3± 0.3
Placebo3.3± 0.3
Maximum Observed Plasma Concentration (Cmax) [Pharmacokinetic] Secondary · Day 1 (hour -1, 1, 2, 4, 6, 8, 12, and 24)

The pharmacokinetic parameters of REL-1017 25 mg and 50 mg will be evaluated on Day 1 through Day 7, Day 8, Day 9, and Day 14 where the data allow.

GroupValue95% CI
REL-1017 25 mg254.5± 60.864
REL-1017 50 mg343.9± 112.36

Adverse events — posted to ClinicalTrials.gov

Time frame: 21 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

REL-1017 25 mg
Serious: 0/19 (0%)
Deaths: 0/19
REL-1017 50 mg
Serious: 0/21 (0%)
Deaths: 0/21
Placebo
Serious: 0/22 (0%)
Deaths: 0/22
Other adverse events (31 terms — click to expand)

ReactionSystemREL-1017 25 mgREL-1017 50 mgPlacebo
ConstipationGastrointestinal disorders
DiarrheaGastrointestinal disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
Abdominal DiscomfortGastrointestinal disorders
DyspepsiaGastrointestinal disorders
SomnolenceNervous system disorders
Upper Respiratory InfectionInfections and infestations
Back PainMusculoskeletal and connective tissue disorders
Weight DecreaseInvestigations
FlatulenceGastrointestinal disorders
VomitingGastrointestinal disorders
DizzinessNervous system disorders
SedationNervous system disorders
Urinary Tract InfectionInfections and infestations
FatigueGeneral disorders
PalpitationsCardiac disorders
PollakiuriaRenal and urinary disorders
PruritiusSkin and subcutaneous tissue disorders
Gastroesophageal Reflux DiseaseGastrointestinal disorders
PresyncopeNervous system disorders
TremorNervous system disorders
InfluenzaInfections and infestations
Limb DiscomfortMusculoskeletal and connective tissue disorders
Blood Pressure IncreasesInvestigations
Abnormal DreamsPsychiatric disorders
RestlessnessPsychiatric disorders
Application Site ErosionGeneral disorders
Feeling of RelaxationGeneral disorders
Drug-Induced Liver InjuryHepatobiliary disorders
HypocalcaemiaMetabolism and nutrition disorders

Data from ClinicalTrials.gov NCT03051256 adverse events section.

Sponsor's own description

This a Phase 2a, multicenter, randomized, double-blind, placebo controlled 3 arm study to assess the safety and tolerability of multiple oral doses of REL-1017 25 mg and 50 mg as adjunctive therapy in the treatment of patients diagnosed with major depressive disorder (MDD). The patients will be adults with MDD who are diagnosed with a current MDE who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication. This population will provide the opportunity to compare the safety and efficacy effects of treatment with an approved antidepressant in conjunction with REL-1017 versus the effects of an antidepressant alone. This study includes in-patient and out-patient periods.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies.
    Li CT, Yang KC, Lin WC. · · 2018 · cited 118× · PMID 30733690 · DOI 10.3389/fpsyt.2018.00767
  2. Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status.
    Henter ID, Park LT, Zarate CA. · · 2021 · cited 104× · PMID 33904154 · DOI 10.1007/s40263-021-00816-x
  3. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
    Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
  4. N-Methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects.
    Fogaça MV, Fukumoto K, Franklin T, Liu RJ, et al · · 2019 · cited 71× · PMID 31454827 · DOI 10.1038/s41386-019-0501-x
  5. Novel drug developmental strategies for treatment-resistant depression.
    Borbély É, Simon M, Fuchs E, Wiborg O, et al · · 2022 · cited 70× · PMID 34822719 · DOI 10.1111/bph.15753
  6. Clinical specificity profile for novel rapid acting antidepressant drugs.
    Scala M, Fanelli G, De Ronchi D, Serretti A, et al · · 2023 · cited 33× · PMID 37381161 · DOI 10.1097/yic.0000000000000488
  7. Glutamatergic Modulators for Major Depression from Theory to Clinical Use.
    McIntyre RS, Jain R. · · 2024 · cited 31× · PMID 39150594 · DOI 10.1007/s40263-024-01114-y
  8. Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.
    Seillier C, Lesept F, Toutirais O, Potzeha F, et al · · 2022 · cited 26× · PMID 36142247 · DOI 10.3390/ijms231810336

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03051256.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing