NRX-101 for Bipolar Depression

(SBD-ASIB Trial)

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

72 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug NRX-101 for treating bipolar depression?

The research does not provide direct evidence for NRX-101, but it mentions that mood stabilizers like lithium and anticonvulsants such as lamotrigine are often used for bipolar depression. Additionally, second-generation antipsychotics like quetiapine and olanzapine have shown effectiveness, which may suggest potential for similar treatments. ^{1 2 3 4 5}

What makes the drug NRX-101 unique for treating bipolar depression?

NRX-101 is unique because it combines D-cycloserine, an antibiotic with potential antidepressant effects, and lurasidone, an atypical antipsychotic, offering a novel approach by targeting both NMDA receptors and serotonin receptors, which may help manage bipolar depression more effectively than traditional treatments. ^{1 3 4 6 7}

What is the purpose of this trial?

This trial tests a two-step treatment for adults with severe bipolar depression and suicidal thoughts. It starts with a quick-acting ketamine dose followed by an oral medication to maintain improvement. The goal is to see if this approach is better than using lurasidone alone. Ketamine has been shown to rapidly reduce depressive and suicidal symptoms in both unipolar and bipolar depression.

Research Team

Martin Brecher, MD

Principal Investigator

VP, Clinical Development, NeuroRx, Inc.

Eligibility Criteria

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

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

My screening exam showed a significant health issue.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Treatment options for bipolar depression: a systematic review of randomized, controlled trials. [2018]

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

Medication treatment of bipolar disorder 2000: a summary of the expert consensus guidelines. [2019]

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

Bipolar depression: pharmacotherapy and related therapeutic strategies. [2019]

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

Management of bipolar depression. [2021]

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

Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. [2018]

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

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

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

Pharmacotherapy of bipolar depression: an update. [2019]