TS-161 for Treatment-Resistant Depression

Overseen By Carlos A Zarate, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: MAOIs, Clozapine, Fluoxetine, others

Disqualifiers: Schizophrenia, Substance abuse, Personality disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 8-9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a new drug, TS-161, can quickly improve symptoms in people with major depressive disorder (MDD) who haven't responded to other antidepressants. Participants will take TS-161 for three weeks and a placebo (a pill with no active medication) for another three weeks, with a drug-free period in between. Those who have experienced depression for at least four weeks and haven't found relief from other treatments might be suitable candidates. Various tests, including interviews, physical exams, and brain scans, will assess the drug's effectiveness. As a Phase 2 trial, this research focuses on measuring how well TS-161 works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in depression treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current psychiatric medications. There will be a tapering-off period followed by a 2-week drug-free period before starting the trial medication.

Is there any evidence suggesting that TS-161 is likely to be safe for humans?

Research has shown that TS-161 is being tested for its safety and effectiveness in treating major depressive disorder. In one study, no deaths or serious side effects occurred. However, 72.2% of participants taking TS-161 reported some side effects, totaling 85. While this might sound concerning, these side effects were not life-threatening.

The option to reduce the dosage from 100 mg to 50 mg if someone cannot tolerate the drug well demonstrates careful monitoring and adjustment for safety. This practice is common in studies to ensure participants' well-being.

Since TS-161 is still under investigation for this use, researchers are collecting more information on its safety. This helps them understand how well people can tolerate the drug and if any side effects can be managed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TS-161 for treatment-resistant depression because it offers a potentially new way to tackle this challenging condition. Unlike standard antidepressants like SSRIs and SNRIs, which primarily work by altering serotonin or norepinephrine levels, TS-161 may target different pathways or receptors in the brain, offering hope for those who haven't responded to existing medications. This novel approach could provide faster relief or work for individuals who have not benefited from traditional treatments, making it an exciting development in the field of mental health.

What evidence suggests that TS-161 might be an effective treatment for depression?

Research has shown that TS-161, which participants in this trial may receive, might help improve depression symptoms by altering brain cell communication. Previous studies suggest that TS-161 could be effective, especially for individuals whose depression hasn't improved with other treatments. It operates differently from many traditional antidepressants, potentially allowing it to work faster. Although still under study, early results appear promising for those with treatment-resistant depression. ^{1 2 4 5 6}

Who Is on the Research Team?

Carlos A Zarate, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

Adults aged 18-65 with major depressive disorder (MDD) who haven't improved after trying at least one antidepressant can join. They must understand the study, consent to it, be willing to stay in a hospital for tests, and avoid alcohol and drugs. Women must use contraception; men must use birth control during the study.

Inclusion Criteria

For females of reproductive potential: use of contraception while in the study and for an additional 4 weeks after stopping the study drug

I have tried at least one antidepressant without success.

I have been diagnosed with major depressive disorder.

Exclusion Criteria

Pregnant participants or those planning to become pregnant in the next 12 to 16 weeks while in the study, or those who are breastfeeding

You have strong thoughts of hurting yourself or someone else.

I do not have any major illnesses like heart or kidney disease that would make joining a study unsafe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Tapering and Drug-Free Period

Participants are tapered off their psychiatric medicines and have a 2-week drug-free period

2 weeks

Inpatient visit at NIH

Treatment

Participants receive TS-161 or placebo for 3 weeks, followed by a 2-3 week drug-free period, then crossover to the alternate treatment for another 3 weeks

8-9 weeks

Multiple visits for interviews, physical exams, psychological tests, MRI, MEG, and ECGs

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• TS-161

Trial Overview The trial is testing TS-161's effectiveness on MDD symptoms compared to a placebo. Participants will stop their current meds, have a drug-free period, then take either TS-161 or placebo for three weeks each with breaks in between. Tests include interviews, physical exams, brain scans (MRI), mood/thinking tasks, and heart monitoring.

How Is the Trial Designed?

Group I: TS-161, then Placebo Experimental Treatment 2 Interventions

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.

Group II: Placebo, then TS-161 Experimental Treatment 2 Interventions

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).

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Taisho Pharmaceutical Co., Ltd.

Industry Sponsor

Trials

40

Recruited

5,300+

Published Research Related to This Trial

In a study of 23 adults with treatment-resistant depression, 91.8% reported significant improvements in emotional and daily functioning after using esketamine nasal spray (ESK) alongside an oral antidepressant (OAD).

Patients noted key benefits of ESK treatment, including its effectiveness, rapid onset of action, and a side-effect profile consistent with existing safety data, leading to high satisfaction rates (100% reported satisfaction).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study. Starr, HL., Abell, J., Larish, A., et al.[2021]

Esketamine nasal spray is a fast-acting treatment option for patients with treatment-resistant depression (TRD), providing a new avenue for those who have not responded to other therapies.

The expert consensus developed in this study offers practical recommendations for clinicians on how to effectively use esketamine nasal spray, addressing pre-treatment considerations and guidelines for administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical recommendations for the management of treatment-resistant depression with esketamine nasal spray therapy: Basic science, evidence-based knowledge and expert guidance. Kasper, S., Cubała, WJ., Fagiolini, A., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04821271

Antidepressant Effects of TS-161 in Treatment-Resistant ... The present Phase 2 proof-of-concept (POC) study is designed to evaluate in subjects with MDD, the antidepressant effects of TS-161.

2. trialx.com trialx.com/clinical-trials/listings/264944/antidepressant-effects-of-ts-161-in-treatment-resistant-depression/

Antidepressant Effects of TS-161 in Treatment-Resistant ... The study will assess the efficacy in improving overall depressive symptomatology and tolerability of TS-161 in treatment-resistant MDD.

3. cochranelibrary.com cochranelibrary.com/central/doi/10.1002/central/CN-02253293/related-content

Antidepressant Effects of TS-161 in Treatment-Resistant ... Mechanism of Action Underlying Ketamine's Antidepressant Effects: the AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression · A randomized ...

4. withpower.com withpower.com/trial/phase-3-depressive-disorder-major-5-2021-d09a9

TS-161 for Treatment-Resistant Depression This trial tests TS-161, a new drug for adults aged 18-65 with treatment-resistant depression. TS-161 aims to improve mood by changing how brain cells ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10503923/

Treatment‐resistant depression: definition, prevalence, ... 30% will meet criteria for TRD. This estimate is derived from efficacy and/or effectiveness research findings.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8832229/

Evaluation of the Safety, Tolerability, and Pharmacokinetic ... Safety and Tolerability​​ There were no deaths or serious AEs during the study. Thirty-nine (72.2%) of 54 subjects in the TS-161 group reported 85 AEs, of which ...