Safety, Tolerability, PK and Efficacy of Single Doses of NV-5138 in Healthy Volunteers and Subjects With Treatment-Resistant Depression

NCT03606395 | Completed Phase 1 FDA Drug

• 1 other identifier: NAV-17A-001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 9

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)

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related adverse events as evidenced by CTCAE v.5.0

  Number of subjects with treatment emergent adverse events

  Baseline through Day 9

Secondary Outcomes (6)

• Maximum plasma concentration (Cmax) of a single dose of NV-5138

  baseline to Day 4

• Terminal elimination half-life (t1/2λz) of a single dose of NV-5138

  baseline to day 4

• Area under the plasma concentration-time curve from zero to infinity (AUC) of a single dose of NV-5138

  baseline to day 4

• Plasma clearance (CL) of a single dose of NV-5138

  baseline to day 4

• Mean residence time (MRT) of a single dose of NV-5138

  baseline to day 4

Study Arms (2)

Single ascending dose_healthy subjects

EXPERIMENTAL

NV-5138: Single dose of 150, 300, 600, 1000, 1600 or 2400 mg single dose of placebo

Drug: NV-5138; Drug: Placebos

Single dose in subjects with TRD

EXPERIMENTAL

NV-5138 oral solution single dose (dose to be determined from Part A) single dose of placebo

Drug: NV-5138; Drug: Placebos

Interventions

NV-5138 DRUG

single ascending dose

Single ascending dose_healthy subjects; Single dose in subjects with TRD

Placebos DRUG

Placebo liquid solution to mimic NV-5138

Single ascending dose_healthy subjects; Single dose in subjects with TRD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• 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.
• 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.
• Subjects must be fluent in English.
• Subjects must be age 18-55, inclusive.
• Subjects must have a body mass index (BMI) between 19 and 30, inclusive.
• Subjects must be age 18-65, inclusive.
• Subjects must have a BMI between 19 and 35, inclusive.
• 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).
• 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.
• 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).
• Subjects must have a Raskin Depression Rating Scale score ≥ 9 at screen and at all evaluations between screen and dose administration (Day 1).

You may not qualify if:

• Subjects must not have:
• A positive pregnancy test result or be breastfeeding.
• A clinically significant illness (including chronic, persistent, or acute infection), medical/surgical procedure, or trauma within 30 days prior to screen or between screen and dose administration (Day 1).
• A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, respiratory, immunologic, hematologic, dermatologic, or neurologic abnormality.
• A history or presence of any disease, condition, or surgery likely to affect drug absorption, distribution, metabolism, or excretion.
• A clinically significant abnormality on physical examination, neurological examination, electrocardiogram (ECG), or laboratory evaluations at screen or between screen and dose administration (Day 1).
• Alanine aminotransferase or aspartate aminotransferase levels greater than 1.5 times the upper limit of normal (ULN) at screen or between screen and dose administration (Day 1).
• Creatinine clearance \< 60 mL/min, according to the Cockcroft-Gault equation.
• Leukocyte or neutrophil counts less than the lower limit of normal (LLN) at screen or between screen and dose administration (Day 1).
• A clinically significant vital signs abnormality at screen or between screen and dose administration (Day 1). This includes, but is not limited to, the following, in the supine position (after 10 minutes supine controlled rest): (a) systolic blood pressure \> 140 mmHg, (b) diastolic blood pressure \> 90 mmHg, or (c) heart rate \< 45 or \> 85 beats per minute.
• A corrected QT interval measurement corrected according to the Fridericia rule (QTcF) \> 450 msec for men and \> 470 msec for women during controlled rest at screen or between screen and dose administration (Day 1), or family history of long-QT syndrome.
• Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgement of the investigator, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
• PR (PQ) interval shortening \< 120 msec (PR \< 120 msec but \> 110 msec is acceptable if there is no evidence of ventricular pre-excitation).
• Persistent or intermittent complete bundle branch block (BBB), or intraventricular conduction delay (IVCD) with QRS \> 110 msec. Subjects with QRS \> 110 msec but \< 115 msec are acceptable if there is no evidence of ventricular hypertrophy or pre-excitation.
• Significant (\> 10%) weight loss or gain within 30 days prior to screen or between screen and dose administration (Day 1).

Sponsors & Collaborators

• Navitor Pharmaceuticals, Inc.: lead

Study Sites (9)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Collaborative Neuroscience Network

Long Beach, California, 90806, United States

Location

Synergy San Diego

San Diego, California, 91945, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Innovative Clinical Research Inc

Hialeah, Florida, 33012, United States

Location

Research Centers of America

Hollywood, Florida, 33024, United States

Location

St. Louis Clinical Trials

St Louis, Missouri, 63141, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Midwest Clinical Research

Dayton, Ohio, 45417, United States

Location

Related Publications (1)

• Targum SD, Sanacora G, Formella AE, Ceresoli-Borroni G, Owen R. A novel, experimental design to assess rapid antidepressant action: Results from a phase 1b randomized trial of NV-5138. J Psychiatr Res. 2026 Jan 7;194:211-220. doi: 10.1016/j.jpsychires.2026.01.006. Online ahead of print.

  PMID: 41512716 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

NV-5138

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Richard Shelton, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, single dose

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 30, 2018
• Study Start: June 6, 2018
• Primary Completion: June 9, 2019
• Study Completion: July 7, 2019
• Last Updated: July 9, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)