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Treatment Resistant DepressionPhase 1NCT03606395

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

A Phase 1 study testing NV-5138 in people with Treatment Resistant Depression, run by Navitor Pharmaceuticals, Inc. at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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) Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Treatment Resistant Depression
What is being tested?
NV-5138
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
9 sitesUnited States
Study dates
6 Jun 2018to 7 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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).
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  • 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).
  • PR (PQ) interval prolongation (> 240 msec), intermittent second-degree (Wenckebach block while asleep or in deep rest is not exclusionary) or third-degree atrioventricular block.
  • 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).
  • A history of seizure.
  • A history of clinically significant head trauma, including closed head injury with loss of consciousness.
  • A history of clinically significant symptomatic orthostatic hypotension (i.e., postural syncope).
  • A history of neuroleptic malignant syndrome.
  • A history of chronic urinary tract infections.
  • A history of cancer within 5 years prior to screen or between screen and randomization (with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin), any history of renal cell carcinoma or breast cancer, or a family history of lymphangioleiomyomatosis in association with tuberous sclerosis complex (TSC-LAM).
  • Any illness or condition that, in the opinion of the investigator, (a) significantly increases the potential risk associated with the subject's participation in the study, (b) decreases the likelihood the subject will complete the study, and/or (c) may confound the results of the study.
  • A diagnosis of intellectual disability (intellectual developmental disorder) or mental retardation.
  • Used prescription or nonprescription medications for attention-deficit hyperactivity disorder (ADHD), narcolepsy, or cognitive enhancement (e.g., methylphenidate, atomoxetine, modafinil, ginkgo biloba, and huperzine A) within 1 month prior to screen or between screen and dose administration (Day 1).
  • Used any vitamin or herbal supplement within 2 weeks prior to dose administration (Day 1), unless approved by the investigator and medical monitor.
  • Consumed alcohol or used any over-the-counter medication (other than up to 3 g per day paracetamol/acetaminophen) within 7 days prior to screen or between screen and dose administration (Day 1).
  • Regularly consumed (e.g., more days than not) excessive quantities of xanthine-containing beverages (e.g., more than five cups of coffee or the equivalent per day) within 30 days prior to screen or between screen and dose administration (Day 1).
  • Donated blood or plasma within 6 weeks prior to screen or between screen and dose administration (Day 1).
  • Used any experimental medication, device, or biologic within 3 months or five half-lives (whichever is longer) prior to screen or between screen and dose administration (Day 1).
  • Currently employed by Navitor Pharmaceuticals, Inc. or by a clinical trial site participating in this study, or a first-degree relative of a Navitor Pharmaceuticals, Inc. employee or of an employee at a participating clinical trial site.
  • Any condition that, in the opinion of the investigator or medical monitor, makes the subject unsuitable for the study.
  • Strenuous physical activity within 1 week prior to dose administration (Day 1).
  • Unsatisfactory venous access.
  • Known or suspected hypersensitivity or idiosyncratic reaction to study drug or study drug excipients.
  • A clinically significant abnormality on electroencephalogram (EEG) at screen (e.g., epileptiform activity).
  • Urine drug screen positive for a drug of abuse.
  • Used any prescription drug within 2 weeks prior to screen, or between screen and dose administration (Day 1).
  • Frequently used any tobacco-containing (e.g., cigar, cigarette or snuff) or nicotine-containing product (e.g., nicotine chewing gum, nicotine plasters, or other product used for smoking cessation) within 3 months prior to screen. Frequent use is defined as 3 or more days per week. Use of any tobacco- or nicotine-containing product is prohibited within 1 week of dose administration (Day 1).
  • Any history of psychiatric disorders, including substance use disorders, according to the DSM-5 criteria.
  • Acute suicidality as evidenced by answering "yes" for Question 4 ("Lifetime") or Question 5 ("Lifetime") on the Columbia-Suicide Severity Rating Scale (C-SSRS), indicating active suicidal ideation with any intent to act, at screen or between screen and dose administration (Day 1), or by answering "yes" for Question 3 ("In the Past Month") on the C-SSRS, indicating active suicidal ideation with any methods (not plan) without intent to act, at screen or between screen and dose administration (Day 1).
  • History of suicidal behavior such that a determination of "yes" is made on the Suicidal Behavior section of the C-SSRS for "Actual Attempt," "Interrupted Attempt," "Aborted Attempt," or "Preparatory Acts or Behavior."
  • Urine drug screen positive for a drug of abuse, except cannabis. Prior use of cannabis is permitted provided the subject agrees to abstain from smoking or ingesting cannabis within 1 week of dose administration (Day 1) and during the study (including the follow-up period), and provided that, in the judgement of the investigator, the subject is likely to be compliant regarding this restriction.
  • Used any psychopharmacologic drug within 2 weeks prior to dose administration (Day 1), except for sleep medication, if used less than 4 days/week within 1 month prior to screen and between screen and dose administration (Day 1).
  • Any history of a psychotic disorder, MDD with psychosis, bipolar or related disorders, post-traumatic stress disorder, obsessive-compulsive disorder (if primary), intellectual disability (DSM-5 diagnostic code 319), borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder, according to the DSM-5 criteria, or any other psychiatric or neurologic disorder or symptom that could pose undue risk to the subject or compromise the study.
  • Moderate or severe substance use disorder within 1 year prior to screen, according to the DSM-5 criteria.
  • Acute suicidality as evidenced by answering "yes" for Question 4 ("In the Past Year") or Question 5 ("In the Past Year") on the C-SSRS, indicating active suicidal ideation with any intent to act, at screen or between screen and dose administration (Day 1), or by answering "yes" for Question 3 ("In the Past Month") on the C-SSRS, indicating active suicidal ideation with any methods (not plan) without intent to act, at screen or between screen and dose administration (Day 1).
  • History of suicidal behavior such that a determination of "yes" is made on the Suicidal Behavior section of the C-SSRS ("In the Past Year") for "Actual Attempt," "Interrupted Attempt," "Aborted Attempt," or "Preparatory Acts or Behavior."
  • MADRS item 10 score of 5 at screen or between screen and dose administration (Day 1).
  • MADRS total score change ≥ 20% between screen and dose administration (Day 1).
  • Covi Anxiety scale score ≥ Raskin Depression Rating Scale score at screen or between screen and dose administration (Day 1).
  • History of clinically significant physical, sexual, or psychological abuse (age ≤ 7 years).

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Hassman Research Institute

    Berlin, New Jersey, 08009

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Midwest Clinical Research

    Dayton, Ohio, 45417

  • MD Clinical

    Hallandale, Florida, 33009

  • Innovative Clinical Research Inc

    Hialeah, Florida, 33012

  • Research Centers of America

    Hollywood, Florida, 33024

  • Collaborative Neuroscience Network

    Long Beach, California, 90806

  • Synergy San Diego

    San Diego, California, 91945

  • St. Louis Clinical Trials

    St Louis, Missouri, 63141

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Single Doses of NV-5138 in Healthy Volunteers and Subjects With Treatment-Resistant Depression

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)

Read the 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.

Being tested
NV-5138, Placebos
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NV-5138Drug

    single ascending dose

  • PlacebosDrug

    Placebo liquid solution to mimic NV-5138

Study groups in NCT03606395
Study groupRoleWhat they receive
Single ascending dose_healthy subjectsExperimentalNV-5138: Single dose of 150, 300, 600, 1000, 1600 or 2400 mg single dose of placebo
Receives: Drug: NV-5138; Drug: Placebos
Single dose in subjects with TRDExperimentalNV-5138 oral solution single dose (dose to be determined from Part A) single dose of placebo
Receives: Drug: NV-5138; Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Number of subjects with treatment emergent adverse events

    Measured: Baseline through Day 9

Secondary outcomes (6)

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

    Maximum plasma concentration (Cmax)

    Measured: baseline to Day 4

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

    Terminal elimination half-life (t1/2λz)

    Measured: baseline to day 4

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

    Area under the plasma concentration-time curve from zero to infinity (AUC)

    Measured: baseline to day 4

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

    Plasma clearance (CL)

    Measured: baseline to day 4

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

    Mean residence time (MRT)

    Measured: baseline to day 4

  6. change from baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score

    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.

    Measured: baseline to Day 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2018
  2. Study start6 Jun 2018
  3. Primary completion9 Jun 2019
  4. Study completion7 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, placebo-controlled, single dose
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03606395
Sponsor's protocol ID
NAV-17A-001
Status last verified
Jul 2019
First submitted
10 Jul 2018
Last updated
9 Jul 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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 Mar;194:211-220. doi: 10.1016/j.jpsychires.2026.01.006. Epub 2026 Jan 7.

    PubMed 41512716

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NV-5138 in people with Treatment Resistant Depression, run by Navitor Pharmaceuticals, Inc. at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 52 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-related adverse events as evidenced by CTCAE v.5.0 (time frame: Baseline through Day 9). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03606395, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2019.

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