NMRA-335140 for Bipolar Depression

No longer recruiting at 24 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Neumora Therapeutics, Inc.

Must not be taking: Antidepressants, Mood stabilizers

Disqualifiers: Bipolar I, Schizophrenia, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NMRA-335140 (also known as BTRX-335140, CYM-53093, or Navacaprant) to evaluate its effectiveness for individuals with Bipolar II disorder currently experiencing major depression. Participants will receive either the study drug or a placebo (a pill with no active ingredient) for six weeks. The goal is to determine if NMRA-335140 can reduce symptoms of depression in these patients. Individuals diagnosed with Bipolar II disorder and currently undergoing a major depressive episode without psychotic features might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators for specific guidance.

Is there any evidence suggesting that NMRA-335140 is likely to be safe for humans?

Research has shown that NMRA-335140 is generally well-tolerated. In studies involving individuals with major depressive disorder, no serious side effects were reported, and participants experienced no major problems with the treatment. Additionally, a long-term safety study lasting 52 weeks found that NMRA-335140 remained safe over time. While it is still being tested for bipolar disorder, past research suggests that the treatment is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for bipolar depression, which typically include mood stabilizers and atypical antipsychotics, NMRA-335140 is unique because it potentially targets different biological pathways. Researchers are excited about this treatment because it might offer a novel mechanism of action that isn't just focused on balancing neurotransmitters like serotonin or dopamine. By exploring a new pathway, NMRA-335140 could provide an alternative for patients who don't respond well to existing medications, offering hope for more personalized and effective treatment options.

What evidence suggests that NMRA-335140 might be an effective treatment for bipolar depression?

Research shows that NMRA-335140 has been tested for its effects on mood disorders. In earlier studies with individuals who have major depressive disorder, this treatment seemed to alleviate symptoms like feeling down and losing interest in activities. However, it did not significantly outperform a placebo in those trials. Despite this, participants generally found it safe and well-tolerated. In this trial, participants will receive either NMRA-335140 or a placebo. Researchers hope that NMRA-335140 might work differently for individuals with Bipolar II disorder, specifically aiding their depressive symptoms. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with Bipolar II Disorder who are currently experiencing symptoms of major depression. Participants must have a stable condition without rapid mood changes and be able to take oral medication. They should not be on certain other medications or therapies for bipolar disorder during the trial.

Inclusion Criteria

Have a MADRS total score of 25 or higher at Screening and Baseline

Participant's current MDE and lifetime history of hypomanic episodes must be confirmed by independent assessment

I have been diagnosed with Bipolar II disorder and am currently experiencing a major depressive episode without psychosis.

Exclusion Criteria

Have currently or in the past year bipolar episodes with mixed features, bipolar II with rapid cycling pattern, or certain comorbid disorders

Have moderate to severe substance or alcohol use disorder within the 12 months prior to screening

Are actively suicidal or homicidal

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either NMRA-335140 or placebo for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NMRA-335140

Trial Overview The study tests NMRA-335140, a potential new treatment for depression in those with Bipolar II Disorder, against a placebo (a pill without active medicine). It's randomized and double-blind, meaning neither participants nor researchers know who gets the real drug or placebo.

How Is the Trial Designed?

Group I: NMRA-335140 80 milligrams (mg) once daily (QD) Experimental Treatment 1 Intervention

Participants will receive a NMRA-335140 tablet at a dose of 80 mg QD.

Group II: Placebo Placebo Group 1 Intervention

Placebo participants will receive matching placebo tablet once daily.

Who Is Running the Clinical Trial?

Neumora Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

2,100+

Published Research Related to This Trial

In a phase 3 study involving 493 adults with bipolar I disorder, cariprazine at a dose of 1.5 mg/day significantly reduced depressive symptoms compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).

The 3.0 mg/day dose did not show significant benefits over placebo, and the safety profile was consistent with previous studies, with common side effects including akathisia and nausea, but minimal weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. Earley, WR., Burgess, MV., Khan, B., et al.[2021]

In a 12-week study involving 232 patients with bipolar II disorder, adding memantine to valproic acid treatment did not show a significant overall improvement compared to valproic acid alone, although both groups experienced reduced depression and mania symptoms.

The study found that patients with the BDNF Val66Met genotype had a significantly better response to the combination treatment of valproic acid and memantine, indicating that genetic factors may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotype variant associated with add-on memantine in bipolar II disorder. Lee, SY., Chen, SL., Chang, YH., et al.[2018]

The systematic review suggests that N-methyl-D-aspartate receptors (NMDARs) may not play a primary role in the pathophysiology of bipolar disorder (BD), but they could be linked to the severity and chronicity of the condition.

Postmortem studies indicate a potential reduction in NMDAR activity in key brain regions associated with BD, which may contribute to neuronal damage and the progression of the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of NMDA receptors in bipolar disorder: A systematic review. Weiss, F., Caruso, V., De Rosa, U., et al.[2023]

Current antidepressant treatments for major depressive disorder (MDD) and bipolar disorder (BD) often have delayed effects and limited efficacy, primarily targeting monoamine systems, while novel glutamate receptor modulators show promise for faster-acting antidepressant effects.

Ketamine, a non-competitive NMDA receptor antagonist, has demonstrated rapid and robust antidepressant effects, leading to the exploration of other NMDA antagonists and glutamate modulators, which may offer similar or improved therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New targets for rapid antidepressant action. Machado-Vieira, R., Henter, ID., Zarate, CA.[2022]

In a study involving 10 bipolar patients and 10 healthy controls, no significant differences in key brain metabolites were found, suggesting that common neurometabolic markers may not differentiate bipolar disorder from healthy individuals.

However, bipolar patients exhibited significantly higher left-to-right myoinositol ratios in the dorsolateral prefrontal cortex, indicating a potential dysfunction in the phosphoinositide-signaling pathway during acute mania, which warrants further investigation in larger, longitudinal studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania. Frey, BN., Folgierini, M., Nicoletti, M., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06429722

NCT06429722 | To Evaluate the Effects of NMRA-335140 ... This is a randomized, double-blind, placebo-controlled pilot study aiming to evaluate the effects of NMRA-335140 on symptoms of major depression in adults ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04221230

Study in Major Depressive Disorder With NMRA-335140 ... A proof of concept (POC) study evaluating the impact of NMRA-335140 (BTRX-335140) relative to placebo on symptoms of major depressive disorder (MDD) in ...

3. ir.neumoratx.com ir.neumoratx.com/news-releases/news-release-details/neumora-therapeutics-announces-initiation-phase-2-study

Neumora Therapeutics Announces Initiation of Phase 2 Study ... Given that in Phase 2 navacaprant demonstrated the ability to meaningfully improve depressed mood and anhedonia in other populations, we believe ...

4. pharmacytimes.com pharmacytimes.com/view/navacaprant-did-not-show-statistically-significant-improvements-when-treating-patients-with-major-depressive-disorder

Navacaprant Did Not Show Statistically Significant ... Despite these findings, navacaprant was generally well-tolerated and safe in patients with major depressive disorder.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40199329/

A Randomized, Double-Blind Phase 2 Clinical Trial Findings/results: At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs placebo (least squares mean difference -1.7 [standard ...

6. clinicaltrials.eu clinicaltrials.eu/inn/nmra-335140/

Nmra-335140 – Application in Therapy and Current ... Long-term safety study: A 52-week study to assess the long-term safety and effectiveness of NMRA-335140 in people with MDD. Phase 2a study for bipolar II ...