NRX-101 for Bipolar Depression With Subacute Suicidal Ideation

Bipolar Depression Clinical Trial

Official title:

A Randomized, Double-Blind Controlled Comparison of NRX-101 to Lurasidone for Adults With Bipolar Depression and Subacute Suicidal Ideation or Behavior

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03395392
• Other study ID #: NRX101_003
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 12, 2022
• Est. completion date: March 30, 2024

Study information

• Verified date: March 2024
• Source: NeuroRx, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: March 30, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder
• Depression
• Depressive Disorder
• Suicidal Ideation

Intervention

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

Locations

Country	Name	City	State
United States	Dent Neurologic Institute	Amherst	New York
United States	ACMR	Atlanta	Georgia
United States	Roots Behavioral Health	Austin	Texas
United States	University of Texas Health Austin	Austin	Texas
United States	Science 37	Culver City	California
United States	iResearch Atlanta, LLC	Decatur	Georgia
United States	Peace Health Medical Group	Eugene	Oregon
United States	JPS Health	Fort Worth	Texas
United States	CBH Health	Gaithersburg	Maryland
United States	Houston Mind and Brain	Houston	Texas
United States	San Marcus Research Clinic, Inc.	Miami Lakes	Florida
United States	Omaha Insomnia and Psychiatric Services	Omaha	Nebraska
United States	Health Texas	Richmond	Texas
United States	iResearch Savannah	Savannah	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
NeuroRx, Inc.	Prevail Infoworks, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in MADRS-10 over 42 Days	Mean change from baseline to endpoint (Day 42/exit) in total MADRS score, a 10-item clinician-rated scale, with each item rated on a 0-6 severity scale (0 Minimum, 60 maximum), where higher scores indicate a worse outcome	Six weeks
Secondary	Mean Change from baseline in CGI-SS	Mean change from baseline to exit (Day 42/exit) in CGI-SS score	Six Weeks
Secondary	Time to Treatment Failure	Time to relapse, where relapse is defined as experiencing a return of suicidality in the Columbia Suicide Severity Rating Scale (C-SSRS) of >=4)), or a return to baseline levels of depression following an improvement of 25% or greater on the MADRS score, or the need to implement a new treatment plan. The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed in the National Institute of Mental Health Treatment of Adolescent Suicide Attempters Study to assess severity and track suicidal events through any treatment. A lower score on the C-SSRS indicates a better outcome (min=0, max=5)	6 weeks

External Links

•   Data Quality Assessment
•   STABIL-B Study Results