NMRA-335140 for Bipolar Depression

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

60 Participants Needed

Trial Summary

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.

What makes the drug NMRA-335140 unique for treating bipolar depression?

NMRA-335140 is unique because it targets the glutamate system, specifically the NMDA receptors, which is different from most current antidepressants that focus on monoamine neurotransmitters like serotonin and dopamine. This approach may offer faster and potentially more effective relief from depressive symptoms in bipolar disorder. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new medication called NMRA-335140 to see if it can help adults with Bipolar II disorder who are experiencing major depression. The medication aims to improve mood and reduce feelings of depression.

Eligibility Criteria

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

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

New targets for rapid antidepressant action. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Genotype variant associated with add-on memantine in bipolar II disorder. [2018]

3. Denmark pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania. [2013]

5. Denmark pubmed.ncbi.nlm.nih.gov

The role of NMDA receptors in bipolar disorder: A systematic review. [2023]