NRX-101 for Bipolar Depression With Subacute Suicidal Ideation

NCT ID: NCT03395392

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-12
• Study Completion Date: 2024-03-30

Brief Summary

NMDA antagonist drugs have shown to reduce symptoms of depression and suicidal ideation. NeuroRx has developed NRX-101 (fixed dose combination of D-cycloserine and lurasidone) for oral use in the treatment of bipolar depression with suicidal ideation. This study will test the hypothesis that NRX-101 is superior to lurasidone alone (standard of care) in maintaining remission from symptoms of depression (primary endpoint) and suicidal ideation or behavior (declared secondary endpoint) over a six week period of twice-daily oral dosing.

Detailed Description

Background and Rationale: NMDA antagonist drugs have shown to reduce symptoms of depression and suicidal ideation. NRX-101 is composed of D-cycloserine (DCS) an NMDA antagonist and lurasidone (5HT2a atypical antipsychotic and antidepressant). In a phase 2 clinical study of bipolar depression and acute suicidal ideation and behavior, (in patients requiring hospitalization) patients received an initial infusion of ketamine and then NRX-101 for 6 weeks. 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 patient study, patients with bipolar depression and subacute suicidality (not requiring hospitalization), ketamine will not be used.

Primary Objective:

• To test the hypothesis that treatment with NRX-101 is superior to standard of care (lurasidone) in improving symptoms of depression as measured by the total Montgomery Åsberg Depression Rating Scale (MADRS-10) score in patients with bipolar depression and subacute suicidal ideation and behavior (SSIB) which does not require hospitalization.

Secondary Objectives:

• To test the hypothesis that treatment with NRX-101 is superior to standard of care (lurasidone) in reducing suicidality in depressed bipolar patients with SSIB, as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)

Methodology: : A multi-center, randomized, double-blind, trial in which patients with bipolar depression (MADRS ≥30) and subacute levels of suicidal ideation (C-SSRS 3 or 4, not requiring hospitalization) are randomized to receive twice daily oral NRX-101 or lurasidone (standard of care).

Conditions

Bipolar Depression; Suicidal Ideation and Behavior

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NRX-101

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

Group Type: EXPERIMENTAL

NRX-101

Intervention Type: DRUG

NRX-101, a fixed dose combination of D-cycloserine+lurasidone will be given twice a day by mouth

Lurasidone

Following study enrollment, subjects will receive twice daily lurasidone

Group Type: ACTIVE_COMPARATOR

Lurasidone HCl

Intervention Type: DRUG

Lurasidone HCl will be given twice a day by mouth

Interventions

NRX-101

NRX-101, a fixed dose combination of D-cycloserine+lurasidone will be given twice a day by mouth

Intervention Type: DRUG

Lurasidone HCl

Lurasidone HCl will be given twice a day by mouth

Intervention Type: DRUG

Other Intervention Names

Latuda

Eligibility Criteria

Inclusion Criteria

• Diagnosed with bipolar disorder by a qualified rater according to the criteria defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and supported by the Mini International Neuropsychiatric Interview (MINI) 7.0.2.
• Confirmed active suicidal ideation (without the intention to act) as evidenced by an answer of 'Yes' on item 3 and/or item 4 and not requiring hospitalization at Screening and an answer of "No" on item 5 of the C-SSRS.
• A total score greater than or equal to 30 on the 10 items of the MADRS.
• Subject has no co-morbidities as ascertained by medical history, physical examination (including measurement of vital signs), clinical laboratory evaluations, and electrocardiogram (ECG)

Exclusion Criteria

• Subject has current DSM-5 diagnosis of moderate or severe substance use disorder (except marijuana or tobacco use disorder) within the 12 months prior to Screening.
• Subject has a lifetime history of:

• phencyclidine (PCP)/ketamine drug abuse, or
• failed use of ketamine for depression or suicidality.
• Subject has schizophrenia or schizoaffective disorder, or any history of psychotic symptoms when not in an acute bipolar mood episode.
• Subject has a current major psychiatric disorder, diagnosed at Screening
• Subject has been prescribed more than one agent in each of the following categories at randomization:

• Approved SSRIs
• Approved serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Approved tetracyclic antidepressants (TeCAs)
• Approved Mood stabilizers (e.g., lithium, valproic acid, and lamotrigine)
• Subject has signs and symptoms of active or residual COVID-19, or unresolved symptoms of COVID-19 that impact health

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prevail Infoworks

INDUSTRY

Sponsor Role: collaborator

NeuroRx, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin Brecher, MD

Role: STUDY_DIRECTOR

NRx Pharma

Andrew A Nierenberg, MD

Role: STUDY_CHAIR

Harvard Medical School (HMS and HSDM)

Jonathan C Javitt, MD, MPH

Role: STUDY_CHAIR

NRx Pharmaceuticals

Locations

Science 37

Culver City, California, United States

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, United States

ACMR

Atlanta, Georgia, United States

iResearch Atlanta, LLC

Decatur, Georgia, United States

iResearch Savannah

Savannah, Georgia, United States

CBH Health

Gaithersburg, Maryland, United States

Omaha Insomnia and Psychiatric Services

Omaha, Nebraska, United States

Dent Neurologic Institute

Amherst, New York, United States

Peace Health Medical Group

Eugene, Oregon, United States

University of Texas Health Austin

Austin, Texas, United States

Roots Behavioral Health

Austin, Texas, United States

JPS Health

Fort Worth, Texas, United States

Houston Mind and Brain

Houston, Texas, United States

Health Texas

Richmond, Texas, United States

Countries

United States

References

Sapko MT, Kolesar C, Sharp IR, Javitt JC. Quality Assurance of Depression Ratings in Psychiatric Clinical Trials. J Clin Psychopharmacol. 2025 Jan-Feb 01;45(1):28-31. doi: 10.1097/JCP.0000000000001936. Epub 2024 Nov 21.

Reference Type: DERIVED

PMID: 39714786 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10423711/

STABIL-B Study Results

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4537055

Data Quality Assessment

Other Identifiers

NRX101_003

Identifier Type: -

Identifier Source: org_study_id