NMRA-335140 for Depression

Recruiting at44 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Neumora Therapeutics, Inc.

Disqualifiers: Personality disorder, Bipolar, Schizophrenia, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the effects of NMRA-335140 (formerly BTRX-335140) on symptoms of depression in participants with Major Depressive Disorder (MDD). The study design consists of a Screening Period (up to 28 days), and a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo). At the completion of the 6-week Treatment Period, participants who complete the study, provide informed consent, and meet the eligibility criteria may enter an open-label extension study (NMRA-335140-501).

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 or your doctor.

What data supports the effectiveness of the drug NMRA-335140 for treating depression?

Research shows that drugs similar to NMRA-335140, which target NMDA receptors, have shown promise in treating depression, especially when other treatments have failed. These drugs, like ketamine, have demonstrated antidepressant effects, suggesting potential benefits for NMRA-335140. ^{1 2 3 4 5}

What safety data exists for NMRA-335140 and similar treatments?

The safety of NMRA-335140, also known as BTRX-335140, CYM-53093, Navacaprant, and other names, is not directly addressed in the provided research articles. However, similar treatments like NMDA antagonists, including ketamine, have known side effects such as changes in mood and thinking. More research is needed to fully understand the safety of these treatments. ^{1 6 7 8 9}

How does the drug NMRA-335140 differ from other depression treatments?

NMRA-335140 is unique because it is an NMDA receptor antagonist, similar to ketamine, which can rapidly improve depression symptoms, especially in patients who do not respond to traditional antidepressants. Unlike standard treatments that target monoaminergic systems, NMDA antagonists work by blocking specific brain receptors involved in mood regulation. ^{1 2 3 7 10}

Research Team

Eligibility Criteria

This trial is for adults with Major Depressive Disorder (MDD) confirmed by a clinical interview, experiencing symptoms for more than 4 weeks but less than 12 months. They must have moderate to severe depression scores and stable symptoms between screening and baseline. Details about specific exclusions are not provided.

Inclusion Criteria

Your current depression has been verified by an external evaluator.

I have been diagnosed with major depression without psychosis.

My current depression episode has lasted more than 4 weeks but less than 12 months.

Trial 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

4 weeks

Open-label extension

Participants may opt into continuation of treatment with NMRA-335140 long-term

Treatment Details

Interventions

• NMRA-335140 (Other)
• Placebo (Other)

Trial Overview The study tests the effects of NMRA-335140 compared to a placebo on depression symptoms over six weeks. Participants will be randomly assigned to receive either the experimental drug or placebo without knowing which one they're getting (double-blind). There's also an optional extension study afterwards.

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 once daily (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

The combination of brexpiprazole and fluoxetine significantly alters amino acid levels in the brain, which may contribute to its antidepressant effects, as shown in a study measuring tissue levels after single and repeated doses.

Specifically, the combination increased GABA levels and affected the D-serine/L-serine and glycine/L-serine ratios in various brain regions, indicating a potential mechanism of action related to NMDAR neurotransmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in amino acid levels in mouse brain regions after adjunctive treatment of brexpiprazole with fluoxetine: comparison with (R)-ketamine. Ma, M., Ren, Q., Fujita, Y., et al.[2018]

In a study involving 117 elderly patients with major depressive disorder, sodium benzoate showed significant improvements in perceived stress and cognitive function compared to placebo, suggesting its potential as a novel treatment for late-life depression.

While sertraline effectively reduced self-reported depressive symptoms, it was associated with a higher risk of increasing low-density lipoprotein levels and had a higher dropout rate compared to sodium benzoate, indicating that sodium benzoate may be a safer and more tolerable option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial. Lin, CH., Wang, SH., Lane, HY.[2022]

A new series of benzopolycyclic amines were developed as NMDA receptor antagonists, showing increased activity compared to earlier analogues.

One of the compounds demonstrated a lower IC50 value than memantine, a drug approved for Alzheimer's, indicating it may be a more potent option for treating related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel benzopolycyclic amines with NMDA receptor antagonist activity. Valverde, E., Sureda, FX., Vázquez, S.[2014]

Recent research highlights the potential of NMDA receptor antagonists, like ketamine and esketamine, as effective treatments for major depressive disorder (MDD), especially for patients who do not respond to traditional antidepressants.

Esketamine's recent FDA approval marks a significant advancement in antidepressant therapy, but further investigation is needed to fully understand the mechanisms and address safety concerns associated with these NMDA receptor-targeting drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on NMDA antagonists in depression. Pochwat, B., Nowak, G., Szewczyk, B.[2020]

NMDA receptor antagonists may help reduce neurotoxic damage in various neurological diseases, suggesting a potential therapeutic role in treating these conditions.

The review highlights clinically tolerated NMDA receptor antagonists that have been used for other medical conditions and can inhibit NMDA receptor activity through mechanisms like open-channel block or redox modification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects for clinically tolerated NMDA antagonists: open-channel blockers and alternative redox states of nitric oxide. Lipton, SA.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. [2021]

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

Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Alterations in amino acid levels in mouse brain regions after adjunctive treatment of brexpiprazole with fluoxetine: comparison with (R)-ketamine. [2018]

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

Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Investigational NMDA receptor modulators for depression. [2013]

6. England pubmed.ncbi.nlm.nih.gov

New targets for rapid antidepressant action. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

NMDA Antagonists for Treatment-Resistant Depression. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Novel benzopolycyclic amines with NMDA receptor antagonist activity. [2014]

9. England pubmed.ncbi.nlm.nih.gov

An update on NMDA antagonists in depression. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Prospects for clinically tolerated NMDA antagonists: open-channel blockers and alternative redox states of nitric oxide. [2022]