Antidepressant Effects of TS-161 in Treatment-Resistant Depression

NCT04821271 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 10000101000101-M
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Major depressive disorder (MDD) is a common, chronic mental illness. It can take weeks to months for antidepressants to work. Researchers want to test a new drug that might act more rapidly. Objective: To see if TS-161 will improve symptoms of depression in people with MDD. Eligibility: Adults ages 18-65 with MDD without psychotic features. Design: Participants will be screened under a separate protocol. They will have blood tests. They will complete surveys about their symptoms. Participants will have an inpatient visit at NIH. Participation may last 12-16 weeks. During the first phase of the study, participants will be tapered off their psychiatric medicines. For 2 weeks they will have a drug-free period. During Phase II participants will take TS-161 or placebo. They will take TS-161 for 3 weeks and placebo for 3 weeks. In between the 3-week time period, they will have 2-3 weeks where they will be drug free. Participants will also have the following tests during this time:

• Interviews
• Physical exams
• Psychological tests and surveys about their symptoms
• Blood draws and urine samples
• They may complete tests of mood and thinking
• Magnetic resonance imaging (MRI): Participants will lie in a machine that takes pictures of their brain.
• Functional MRIs: They will perform tasks displayed on a computer screen inside the MRI scanner
• Magnetoencephalography (MEG): Participants will lie down and do tasks of memory, attention, and thinking. A cone lowered on their head will record brain activity.
• Electrocardiograms to record the heart s electrical activity. Electrodes will be placed on the skin....

Conditions

Major Depressive Disorder; Treatment-Resistant Depression; Depression

Keywords

Biomarker; Neurobiology; Glutamate; Magnetoencephalography; Magnetic Resonance Spectroscopy

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score

  Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline and day 21 (week 3). The MADRS is a 10-item clinician-rated questionnaire to evaluate depressive symptoms in adults and for the assessment of any changes to those symptoms. Each item is rated on a scale of 0 to 6 (0 = absent, 6 = severe) with total score range between 0 and 60. Higher score indicates worsening depression. For each crossover period, the MADRS was completed 60 minutes before intervention (baseline) and 230 minutes, 1, 2, 3, 7, 14, and 21 days following the first dose. Analysis was the change in total score between baseline and day 21. Change was calculated as the estimated marginal MADRS total score means using a linear mixed model regression.

  Baseline and day 21 (week 3)

Secondary Outcomes (19)

• Montgomery-Asberg Depression Rating Scale (MADRS) Mean Total Score

  230 minutes following the first treatment dose

• Montgomery-Asberg Depression Rating Scale (MADRS) Mean Total Score

  Day 1 following the first treatment dose

• Montgomery-Asberg Depression Rating Scale (MADRS) Mean Total Score

  Day 2 following the first treatment dose

• Montgomery-Asberg Depression Rating Scale (MADRS) Mean Total Score

  Day 3 following the first treatment dose

• Montgomery-Asberg Depression Rating Scale (MADRS) Mean Total Score

  Day 7 following the first treatment dose

Study Arms (2)

TS-161, then Placebo

EXPERIMENTAL

Participants with major depressive disorder (MDD) were randomized to receive TS-161 100mg capsule orally once per day for three weeks (with option to decrease to 50 mg due to drug intolerance), followed by Placebo capsule orally once per day for three weeks.

Other: Placebo; Drug: TS-161

Placebo, then TS-161

EXPERIMENTAL

Participants with major depressive disorder (MDD) were randomized to receive Placebo capsule orally once per day for three weeks, followed by TS-161 100mg capsule orally once per day for three weeks (with option to decrease to 50 mg due to drug intolerance).

Other: Placebo; Drug: TS-161

Interventions

Placebo OTHER

Participants received Placebo capsule orally once daily for three weeks.

Placebo, then TS-161; TS-161, then Placebo

TS-161 DRUG

Participants received TS-161 50-100 mg capsule orally once daily for three weeks. TS-161 is a mGlu2/3 receptor antagonist prodrug.

Placebo, then TS-161; TS-161, then Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants may be eligible for this study if they:
• Are able to understand the study and can provide your own consent.
• Are willing to undergo all study procedures and are available for the duration of the study.
• Are aged 18 to 65.
• Have major depressive disorder.
• Have a current episode of depression lasting at least 4 weeks.
• Ability to take oral medication.
• Have not responded to at least one antidepressant.
• For females of reproductive potential: use of contraception while in the study and for an additional 4 weeks after stopping the study drug.
• For males of reproductive potential: use of condoms or other types of birth control with partner while in the study and for an additional 3 months after stopping the study drug.
• Agree to be hospitalized at the NIH Clinical Center.
• Abstain from alcohol and drug use while in the study.

You may not qualify if:

• Participants may not be eligible for this study if they:
• Are taking any medications that might make it unsafe for you to receive TS-161 or might interfere with our study results.
• Have been treated with a reversible monoamine oxidase inhibitor (such as phenelzine (Nardil) and tranylcypromine (Parnate)), clozapine, or electroconvulsive therapy (ECT) less than 4 weeks before Phase II.
• Have been treated with fluoxetine, aripiprazole, or brexpiprazole less than 5 weeks before Phase II.
• Have ever undergone deep brain stimulation.
• Have taken ketamine or esketamine for the treatment of depression but did not respond.
• Are unwilling to stop undergoing one-on-one psychotherapy for the duration of the study.
• Are pregnant or plan to become pregnant in the next 12 to 16 weeks while in the study, or are breast-feeding.
• Have schizophrenia or any other psychotic disorder.
• Had significant drug or alcohol dependence or abuse in the past 3 months (except for nicotine or caffeine), or are currently using illicit substances.
• Have been diagnosed with borderline or antisocial personality disorder.
• Had a head injury that caused a loss of consciousness for more than 5 minutes (for the brain imaging).
• Have a medical illness that might make your participation unsafe, such as heart (including coronary artery disease, atherosclerotic ischemic stroke, and atrial fibrillation), liver, respiratory, blood, immune, or kidney disease or a seizure disorder, based on our evaluation.
• Have abnormal results on blood and urine tests we will do.
• Have significant suicidal or homicidal thoughts.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead
• Taisho Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Zarate, Carlos
• Organization: National Institute of Mental Health

zaratec@mail.nih.gov

+1 301 451 0861

Study Officials

• Carlos A Zarate, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2021
• First Posted: March 29, 2021
• Study Start: June 10, 2021
• Primary Completion: May 23, 2024
• Study Completion: May 23, 2024
• Last Updated: June 10, 2025
• Results First Posted: June 10, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Starting within one year of completion of the study.
• Access Criteria: Branch Chief will review requests and access will need to be approved by the NIMH/DIRP SD and OCD NIMH and the NIH Institutional Review Board (IRB).

Locations

US (1)