Treatment Resistant Depression
Conditions
Brief summary
This study will evaluate the efficacy and safety of NV-5138 in adults with TRD
Detailed description
The is a multicenter, randomized, double-blind, flexible- dose, placebo-controlled, parallel design of adjunctive NV-5138 in adults with TRD.
Interventions
DRUGNV-5138
NV-5138 is a novel, orally bioavailable, selective, direct enhancer of mTORC1 cellular signaling
DRUGmatched placebo
matched placebo oral capsules
Sponsors
Navitor Pharmaceuticals, Inc.
Supernus Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
matched placebo
Intervention model description
randomized, double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, aged 18 to 70 years at Screening. * Diagnosis of Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) for either recurrent or single episode MDD without psychotic features that is confirmed by the Mini International Neuropsychiatric Interview (MINI). * Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≥24 for the current MDE at all Screening visits and Baseline (Day 1). * CGI-S score of ≥4 (moderately ill or worse) at the Screening visits and Baseline. * History of inadequate response to ≥1 but ≤4 prior ADT therapies (including the current ADT for the current MDE) ≥ 2 weeks at Screening and ≥ 8 weeks at Baseline. * Stable therapeutic dose of one of the following ADTs for the current MDE for ≥2 weeks prior to Screening and maintain the therapeutic dose throughout the study: citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine (IR or XR), desvenlafaxine, vilazodone, levomilnacipran, vortioxetine, bupropion or dextromethorphan//bupropion. * Detectable blood level of the approved ADT at Visits 1 and 2 of the Screening Period.
Exclusion criteria
* MADRS Total Score improvement of ≥25% from the highest to the lowest score during the Screening Period and Baseline. * Clinically significant abnormal laboratory profiles, vital signs, or electrocardiograms (ECGs), per Investigator judgment. * Judged by the Investigator to be at significant risk for suicide or answers 'Yes' to items 4 or 5 on the Suicidal Ideation section of the C-SSRS in the 1 year before Screening; a history of suicide attempt in the last 2 years; or more than 2 lifetime suicide attempts. * History of psychotic disorder, including but not limited to schizophrenia, MDD with psychotic features, or bipolar I/II disorder with and without psychotic features. * Diagnosis within 12 months before Screening or current diagnosis of PTSD, OCD, panic disorder, intellectual disability, autism, acute stress disorder, or Cluster A or B personality disorder (per DSM-5 criteria). * History of substance use disorder within 6 months prior to Screening or currently using or had positive results (UDS) at Screening or Baseline for drugs of abuse. * History of alcohol and cannabis use disorder within 6 months prior to Screening and had a positive alcohol test at Baseline or a positive UDS for cannabis at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 4 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. | Baseline to Week 4 | MADRS is a 10-item scale (Reported sadness, Apparent sadness, Inner tension, Reduced sleep, Reduced appetite, Concentration difficulties, Lassitude, Inability to feel, Pessimist thoughts, and Suicidal thoughts) where each item is scored from 0 to 6. The total score is the sum of the 10 items ranging from 0 to 60 where higher scores indicate more severe depression, and lower scores are better outcomes. A negative change from baseline indicates improvement in depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Each Scheduled Week in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. | Baseline to Weeks 1, 2 and 3 | MADRS is a 10-item scale (Reported sadness, Apparent sadness, Inner tension, Reduced sleep, Reduced appetite, Concentration difficulties, Lassitude, Inability to feel, Pessimist thoughts, and Suicidal thoughts) where each item is scored from 0 to 6. The total score is the sum of the 10 items ranging from 0 to 60 where higher scores indicate more severe depression, and lower scores are better outcomes. A negative change from baseline indicates improvement in depressive symptoms. |
| Change From Baseline to Each Scheduled Week in the Clinical Global Impression - Severity of Illness Score (CGI-S). | Baseline to Weeks 1, 2, 3 and 4 | CGI-S is a single-item clinician rating of the clinician's assessment of the severity of symptoms in relation to the clinician's total experience with patients with that condition. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = "normal not at all ill" and 7 = "among the most extremely ill patients". Successful therapy is indicated by a lower overall score. A negative change from baseline indicates improvement in depressive symptoms. |
| Change From Baseline to Each Scheduled Week in the The Hamilton Depression Rating Scale - 6 Items (HAM-D6) Total Score. | Baseline to Weeks 1, 2, 3 and 4 | The Hamilton Depression Rating Scale - 6 Items is a diagnostic questionnaire used to measure the severity of depressive episodes. It consists of 6 items (depressed mood, work and activities, somatic symptoms general, feeling of guilt, anxiety psychic, retardation) and each question is scored from 0 to 4 except for one item, somatic symptoms general, which is scored from 0 - 2 for a total score ranging 0 to 22. Higher scores indicate more severe conditions. A negative change from baseline indicates improvement in depressive symptoms. |
| Suicidal Ideation and Behavior as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline to Weeks 1, 2, 3 and 4 | C-SSRS assessment included "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Number of participants with a response of 'yes' to any suicidal ideation or suicidal behavior item as measured by C-SSRS is reported. |
Countries
United States
Contacts
STUDY_DIRECTORThomas Laage, MD
Medical Monitor
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 13.91 |
| CGI-S | 4.7 units on a scale STANDARD_DEVIATION 0.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 183 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| HAM-D6 Total Score | 11.9 units on a scale STANDARD_DEVIATION 2.08 |
| MADRS Total Score | 33.3 units on a scale STANDARD_DEVIATION 4.65 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 204 Participants |
| Region of Enrollment United States | 126 Participants |
| Sex: Female, Male Female | 162 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 126 | 0 / 122 |
| other Total, other adverse events | 28 / 126 | 28 / 122 |
| serious Total, serious adverse events | 1 / 126 | 2 / 122 |
Outcome results
None listed