NRX-101 for Bipolar Depression

(SBD-ASIB Trial)

Not currently recruiting at 3 trial locations

Overseen By Martin Brecher, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NeuroRx, Inc.

Must not be taking: Antidepressants, Mood stabilizers

Disqualifiers: Substance use disorder, Schizophrenia, Hypertension, Diabetes, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new treatment, NRX-101, for individuals with bipolar depression, focusing on reducing symptoms of depression and suicidal thoughts. NRX-101 combines D-cycloserine and lurasidone (an antipsychotic medication) and is administered after an initial ketamine treatment to help maintain mood stability. Participants will receive either NRX-101 or lurasidone alone to determine which is more effective over six weeks. This trial may suit those diagnosed with bipolar disorder who have responded well to a prior ketamine infusion. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial allows participants to continue certain stable medications, like psychotherapy and hypnotic therapy, if they have been stable for a specified period before screening. However, some psychotropic medications are exclusionary, and participants cannot be on more than one agent in certain categories like antidepressants and mood stabilizers. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NRX-101, a combination of D-cycloserine and lurasidone, is generally safe for people. Patients using NRX-101 maintained their improvements better than those using only lurasidone. One study reported no major safety issues, and the treatment proceeded smoothly. An independent safety board found no problems with NRX-101 and recommended the continuation of the clinical trial to accept new participants. This suggests that the treatment is considered safe based on current evidence. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

NRX-101 is unique because it combines D-Cycloserine and lurasidone, offering a novel approach to treating bipolar depression. Unlike most treatments that primarily focus on neurotransmitter balance, NRX-101 targets the NMDA receptor, potentially providing more effective symptom relief. Researchers are excited about this treatment because it could offer a faster onset of action and improved outcomes compared to standard options like lithium or valproate.

What evidence suggests that NRX-101 might be an effective treatment for bipolar depression?

Research has shown that NRX-101, a combination of D-cycloserine and lurasidone, effectively treats bipolar depression. In this trial, some participants will receive NRX-101, which studies have demonstrated works better than lurasidone alone in controlling depression symptoms. Specifically, NRX-101 improved mood and reduced suicidal thoughts over six weeks. Previous research suggests that NRX-101 maintains improvements in depression and suicidal thoughts more effectively than lurasidone alone. The FDA has given this treatment special recognition, highlighting its potential benefits. ^{2 3 4 6 7}

Who Is on the Research Team?

Martin Brecher, MD

Principal Investigator

VP, Clinical Development, NeuroRx, Inc.

Are You a Good Fit for This Trial?

Adults aged 18-65 with severe bipolar depression and suicidal thoughts, responding to initial treatment under NCT03396601. Participants must be in good health, have a stable living situation, reliable informant, and if female, use effective birth control or be non-childbearing. Excludes those with other major psychiatric disorders as primary focus or certain physical conditions.

Inclusion Criteria

A subject will be eligible for inclusion in this study based on successful response to infusion under NCT03396601

In good general health

I have been in stable psychotherapy for at least 3 months.

Exclusion Criteria

My screening exam showed a significant health issue.

Has dementia, delirium, amnestic, or any other cognitive disorder

History of schizophrenia or schizoaffective disorder or any history of psychotic symptoms when not in an acute bipolar mood episode

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Stabilization

Participants receive a single infusion of ketamine (NRX-100) for rapid stabilization of symptoms of depression and suicidal ideation

1 day

1 visit (in-person)

Treatment

Participants receive oral NRX-101 or lurasidone for maintenance of remission from symptoms of depression and suicidal ideation

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lurasidone HCl
• NRX-101

Trial Overview The trial tests NRX-101 for maintaining remission from severe bipolar depression after initial stabilization with IV ketamine (NRX-100). NRX-101 is compared to Lurasidone alone over six weeks of oral dosing. The study aims to see if NRX-101 better prevents relapse and reduces suicidal thoughts.

How Is the Trial Designed?

Group I: NRX-101 Experimental Treatment 1 Intervention

Subjects will be treated with oral NRX-101 (fixed dose combination of D-Cycloserine/lurasidone) that will be titrated to a combined dose of 950mg/66mg per day.

Group II: Lurasidone comparator Active Control 1 Intervention

Subjects will be treated with oral lurasidone in a matched placebo capsule that will be titrated to a dose of 66 mg per day

Who Is Running the Clinical Trial?

NeuroRx, Inc.

Lead Sponsor

Trials

14

Recruited

1,600+

Vanguard, Inc

Collaborator

Trials

1

Recruited

70+

Target Health Inc.

Industry Sponsor

Trials

7

Recruited

520+

Published Research Related to This Trial

In a meta-analysis of 19 studies, quetiapine and the olanzapine-fluoxetine combination were found to be the most effective treatments for bipolar depression, showing significant reductions in depression scores compared to placebo.

Not all medications tested, such as lamotrigine, paroxetine, aripiprazole, and lithium, demonstrated efficacy, highlighting the variability in treatment responses and the need to consider safety and tolerability when choosing a treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for bipolar depression: a systematic review of randomized, controlled trials. Vieta, E., Locklear, J., Günther, O., et al.[2018]

A new expert consensus guideline for treating bipolar disorder emphasizes the use of mood stabilizers, particularly lithium and divalproex, as foundational treatments for both acute and preventive care, especially for mixed or dysphoric mania.

The guidelines recommend combining standard antidepressants with mood stabilizers for severe depression, with specific preferences for medications like bupropion and SSRIs, while also supporting the use of atypical antipsychotics for managing mania or depression with psychosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication treatment of bipolar disorder 2000: a summary of the expert consensus guidelines. Kahn, DA., Sachs, GS., Printz, DJ., et al.[2019]

Bipolar depression is often more significant than manic episodes, with depressive episodes being more frequent and longer-lasting, which can lead to a higher risk of suicide; thus, accurate diagnosis is crucial to avoid delays in treatment.

Initial treatment for bipolar I depression should focus on mood stabilizers rather than antidepressants alone, with the combination of fluoxetine and olanzapine being the first specifically approved therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar depression: issues in diagnosis and treatment. Thase, ME.[2007]

Bipolar affective disorder is challenging to treat due to frequent depressive episodes that are often misdiagnosed, leading to delays in effective therapy and increased risk of treatment-emergent affective switches when using antidepressants alone.

Currently, the only FDA-approved treatment for bipolar depression is the combination of olanzapine and fluoxetine, while conventional mood stabilizers are preferred as first-line therapies, with atypical antipsychotics like quetiapine awaiting approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of bipolar depression: an update. Thase, ME.[2019]

Mood stabilizers are recommended as the first-line treatment for type I bipolar depression due to their effectiveness in long-term prevention of depressive episodes, while the necessity of mood stabilizers for type II bipolar depression is less clear.

For depressive episodes that do not respond to mood stabilizers, antidepressants like bupropion and selective serotonin reuptake inhibitors are recommended, with a low risk (5% to 10%) of inducing hypomania or mania when used alongside mood stabilizers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar depression: pharmacotherapy and related therapeutic strategies. Thase, ME., Sachs, GS.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37573534/

NRX-101 (D-cycloserine plus lurasidone) vs. ... The fixed-dose combination of DCS and lurasidone was significantly more effective than lurasidone alone in maintaining improvement in depression (MADRS LMS ...

2. journalbipolardisorders.springeropen.com journalbipolardisorders.springeropen.com/articles/10.1186/s40345-023-00308-5

NRX-101 (D-cycloserine plus lurasidone) vs. lurasidone for ... A fixed-dose combination of oral D-cycloserine (DCS) and lurasidone (NRX-101) can maintain improvement more effectively than lurasidone alone.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03395392

NRX-101 for Bipolar Depression With Subacute Suicidal ... In that phase 2 study, NRX-101 showed the ability to maintain remission from depression and suicidality over 6 weeks when taken twice daily. In this current out ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/92/NCT03395392/Prot_001.pdf

NRX-101_003 Protocol The data below provides evidence of efficacy from a study of NRX-101 versus Lurasidone in patients with severe bipolar depression (MADRS ≥ 30) ...

5. medrxiv.org medrxiv.org/content/10.1101/2022.08.11.22278658v1

NRX-101 (D-cycloserine plus lurasidone) vs. ... The fixed dose combination of DCS and lurasidone was significantly more effective than lurasidone alone in maintaining improvement in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10423711/

NRX-101 (D-cycloserine plus lurasidone) vs ... - PubMed Central A fixed-dose combination of oral D-cycloserine (DCS) and lurasidone (NRX-101) can maintain improvement more effectively than lurasidone alone.

7. prnewswire.com prnewswire.com/news-releases/nrx-pharmaceuticals-reports-recommendations-of-data-safety-monitoring-board-for-trial-of-nrx-101-in-patients-with-severe-bipolar-depression-and-subacute-suicidal-ideation-or-behavior-301736992.html

NRx Pharmaceuticals Reports Recommendations of Data ... The Independent Data Safety Monitoring Board identified no safety concerns and issued a recommendation to continue trial enrollment.