Treatment Resistant Depression
Conditions
Brief summary
Randomized, two-part, placebo-controlled study of single ascending doses of NV-5138 in healthy volunteers, and a single dose of NV-5138 in subjects with Treatment-Resistant Depression (TRD)
Detailed description
This is a randomized, two-part, double-blind, placebo-controlled study of single ascending dosage levels of NV-5138 in healthy volunteers and a single dose of NV-5138 in subjects with TRD. The study includes an up to 28-day screening period, an in-house period during which NV-5138 or placebo will be administered, and a 3- to 7-day follow-up period after discharge. In Part A of the study (single-ascending-dose \[SAD\] portion in healthy volunteers), up to approximately 48 healthy volunteers will be randomly assigned to double-blind treatment. Eight (8) subjects will be randomized in each of six dosage-level cohorts (150, 300, 600, 1000, 1600, or 2400 mg NV-5138, or placebo, administered as an oral solution). Within each cohort, six subjects will be randomized to receive NV-5138 and two subjects will be randomized to receive placebo. Each subject will receive only one dose of either NV-5138 or placebo on Day 1. Within each cohort, initially one subject will receive NV-5138 and one subject will receive placebo. Provided no clinically significant safety issues are noted in the 24 hours after dosing the initial two subjects in the cohort, the six subjects remaining in the cohort may be dosed. In Part B of the study (single-dose portion in subjects with TRD), up to approximately 40 subjects will be randomly assigned to double-blind treatment in one cohort. The dosage level for this cohort will be determined based on the safety, tolerability, and pharmacokinetic data from Part A of the study. However, in no case will the dose in Part B of the study exceed the highest dose administered in Part A of the study. Within this cohort, after potential eligibility has been confirmed by a site-independent review process, twenty (20) subjects will be randomized to receive NV-5138 and twenty (20) subjects will be randomized to receive placebo.
Interventions
DRUGNV-5138
single ascending dose
DRUGPlacebos
Placebo liquid solution to mimic NV-5138
Sponsors
Navitor Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Intervention model description
Randomized, placebo-controlled, single dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
(Subjects in Part A or Part B): 1. Subjects must understand the nature of the study and must provide signed and dated written informed consent before the conduct of any study-related procedures. 2. Female subjects must be postmenopausal, surgically sterile, or agree to use one or more of the following forms of contraception from the time of signing the informed consent form through at least 30 days following the administration of test article: hormonal (i.e., oral, transdermal, implant, or injection); double barrier (i.e., condom, diaphragm with spermicide); intrauterine device (IUD); or vasectomized partner (6 months minimum). Postmenopausal women must have had ≥ 12 months of spontaneous amenorrhea with follicle-stimulating hormone \[FSH\] ≥ 30 mIU/mL. Surgically sterile women are defined as those who have had a hysterectomy, bilateral ovariectomy, or bilateral tubal ligation. All women must have a negative pregnancy test result before administration of test article. 3. Male subjects who are biologically capable of having children (i.e., non-vasectomized) must agree to use one or more of the above forms of birth control for either themselves or their partner(s), as appropriate, from the time of signing the informed consent form through at least 90 days following the administration of test article. 4. Subjects must be, in the opinion of the investigator, able to participate in all scheduled evaluations, likely to complete all required tests, and likely to be compliant. 5. Subjects must be fluent in English. Inclusion Criteria (Subjects in Part A Only): 6. Subjects must be age 18-55, inclusive. 7. Subjects must have a body mass index (BMI) between 19 and 30, inclusive. Inclusion Criteria (Subjects in Part B Only): 8. Subjects must be age 18-65, inclusive. 9. Subjects must have a BMI between 19 and 35, inclusive. 10. Subjects must have a diagnosis of major depressive disorder (MDD) without psychotic features, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, based on clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI). 11. Subjects must have had an inadequate response to at least one but no more than four antidepressants (stable, adequate dose, at least 6 weeks treatment) in the current episode of depression. The Massachusetts General Hospital-Antidepressant Treatment Response Questionnaire (MGH-ATRQ) will be used to assess antidepressant treatment response. Less than 50% improvement will be considered inadequate response. 12. Subjects must have a Montgomery-Åsburg Depression Rating Scale (MADRS) total score ≥ 21 at screen and at all evaluations between screen and dose administration (Day 1). 13. Subjects must have a Raskin Depression Rating Scale score ≥ 9 at screen and at all evaluations between screen and dose administration (Day 1).
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-related adverse events as evidenced by CTCAE v.5.0 | Baseline through Day 9 | Number of subjects with treatment emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal elimination half-life (t1/2λz) of a single dose of NV-5138 | baseline to day 4 | Terminal elimination half-life (t1/2λz) |
| Area under the plasma concentration-time curve from zero to infinity (AUC) of a single dose of NV-5138 | baseline to day 4 | Area under the plasma concentration-time curve from zero to infinity (AUC) |
| Maximum plasma concentration (Cmax) of a single dose of NV-5138 | baseline to Day 4 | Maximum plasma concentration (Cmax) |
| Mean residence time (MRT) of a single dose of NV-5138 | baseline to day 4 | Mean residence time (MRT) |
| change from baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | baseline to Day 2 | The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts and suicidal thoughts. |
| Plasma clearance (CL) of a single dose of NV-5138 | baseline to day 4 | Plasma clearance (CL) |
Countries
United States
Outcome results
None listed