What side effects are associated with this type of intervention?

D-cycloserine, an NMDA receptor antagonist, is generally well-tolerated but can cause side effects such as headache, dizziness, and fatigue. Lurasidone, an atypical antipsychotic, may cause side effects including weight gain, sedation, nausea, and extrapyramidal symptoms (e.g., tremors, rigidity). Other common treatments for depression, such as SSRIs, can cause gastrointestinal disturbances, sexual dysfunction, and insomnia, while mood stabilizers like lithium can lead to weight gain, thyroid dysfunction, and renal issues.

What prior FDA approvals exist?

The FDA has approved several treatments for Depression and Bipolar Disorder that are similar to the components of NRX-101. For NMDA receptor antagonists, Esketamine (Spravato) has been approved for treatment-resistant depression. It works by modulating the NMDA receptor, similar to D-cycloserine. For atypical antipsychotics, Lurasidone (Latuda) itself is FDA-approved for the treatment of depressive episodes associated with Bipolar I Disorder. Other atypical antipsychotics approved for Bipolar Disorder include Quetiapine (Seroquel), Olanzapine (Zyprexa), and Aripiprazole (Abilify). These medications help manage mood swings and depressive symptoms in bipolar patients.

What other types of research exist?

Promising novel alternatives to NRX-101 for treating depression in bipolar disorder patients include: 1) CP-101,606, an NR2B subunit-selective NMDA receptor antagonist, which has shown antidepressant efficacy in treatment-refractory major depressive disorder. 2) MK-0657, another NR2B antagonist, which has been evaluated for treatment-resistant major depressive disorder. Both alternatives target the NMDA receptor, similar to D-cycloserine in NRX-101.

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NMDA Antagonist

NRX101 for Bipolar Depression (MBD Trial)

Phase 2 & 3

Waitlist Available

Research Sponsored by NeuroRx, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

Subject has signs and symptoms of active or residual COVID-19, or unresolved symptoms of COVID-19 that impact health

Timeline

Screening 3 weeks

Treatment Varies

Follow Up six weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new pill called NRX-101, which combines two drugs to help improve mood and reduce suicidal thoughts in people with bipolar depression who are not in the hospital. The goal is to see if this new treatment works better than the current standard treatment.

Who is the study for?

This trial is for adults with bipolar depression who currently have suicidal thoughts but don't need hospitalization. They must score ≥30 on the MADRS, a depression rating scale, and meet DSM-5 criteria for bipolar disorder without other major psychiatric disorders or recent substance abuse.

What is being tested?

The study compares NRX-101, a combination of D-cycloserine and lurasidone, to lurasidone alone in maintaining remission from bipolar depression and reducing suicidal thoughts over six weeks with twice-daily oral dosing.

What are the potential side effects?

Potential side effects may include those commonly associated with NMDA antagonists such as dizziness, nausea, headache; or antipsychotics like lurasidone which can cause restlessness, muscle stiffness, weight gain.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am experiencing ongoing or residual symptoms from COVID-19.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from Baseline in MADRS-10 over 42 Days

Secondary study objectives

Mean Change from baseline in CGI-SS

Time to Treatment Failure

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: NRX-101Experimental Treatment1 Intervention

Following study enrollment and randomization, subjects will receive twice daily NRX-101

Group II: LurasidoneActive Control1 Intervention

Following study enrollment, subjects will receive twice daily lurasidone

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

NRX-101

2022

Completed Phase 3

~90

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

D-cycloserine is a partial agonist at the glycine site of the NMDA receptor, which plays a role in modulating glutamatergic neurotransmission. This mechanism is thought to aid in reducing symptoms of depression and suicidal ideation by enhancing neuroplasticity and cognitive function. Lurasidone, an atypical antipsychotic, works primarily by antagonizing dopamine D2 and serotonin 5-HT2A receptors, which helps stabilize mood and reduce psychotic symptoms. These mechanisms are crucial for patients with depression and bipolar disorder as they target different pathways involved in mood regulation and cognitive function, potentially offering a more comprehensive approach to treatment.

Efficacy of adjunctive D-Cycloserine for the treatment of schizophrenia: a systematic review and meta-analysis of randomized controlled trials.Glutamatergic drugs for schizophrenia.