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NRX101 for Bipolar Depression and Sub-acute Suicidal Ideation and Behavior

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03395392
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : October 5, 2022
Sponsor:
Collaborator:
Prevail Infoworks, Inc
Information provided by (Responsible Party):
NeuroRx, Inc.

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.

Condition or disease Intervention/treatment Phase
Bipolar Depression Suicidal Ideation and Behavior Drug: NRX-101 Drug: Lurasidone HCl Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Participants and Care Providers will be masked with regard to medication administered.
Primary Purpose: Treatment
Official Title: Comparison of NRX-101 to Standard of Care (Lurasidone) for Bipolar Depression With Subacute Suicidal Ideation and Behavior
Actual Study Start Date : May 12, 2022
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
Experimental: NRX-101
Following study enrollment and randomization, subjects will receive twice daily NRX-101
Drug: NRX-101
NRX-101, a fixed dose combination of D-cycloserine+lurasidone will be given twice a day by mouth

Active Comparator: Lurasidone
Following study enrollment, subjects will receive twice daily lurasidone
Drug: Lurasidone HCl
Lurasidone HCl will be given twice a day by mouth




Primary Outcome Measures :
  1. Change from Baseline in MADRS (Montgomery Åsberg Depression Rating Scale) score at Day 42 [ Time Frame: Six weeks ]
    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


Secondary Outcome Measures :
  1. Time to Relapse [ Time Frame: 6 weeks ]
    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)

  2. Percent in remission [ Time Frame: Day 42 ]
    Percent in remission at Day 42/exit

  3. Mean Change from baseline in C-SSRS score [ Time Frame: Day 42 ]
    Mean change from baseline to endpoint (Day 42/exit) in C-SSRS score



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03395392


Contacts
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Contact: NRx Clinical Contact Line (855) 367-9101 clinicaltrials@nrxpharma.com
Contact: NRx Clinical Contact Line 4842546134 ext 733

Locations
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United States, Florida
San Marcus Research Clinic, Inc. Recruiting
Miami Lakes, Florida, United States, 33014
Contact: janeth bobadilla    305-424-7420    jbobadilla@sanmarcusrc.com   
Principal Investigator: nancy navarro gonzalez, MD         
United States, Georgia
ACMR Recruiting
Atlanta, Georgia, United States, 30331
Contact: Lauren White    404-881-5800    l.white@cenexel.com   
Principal Investigator: Maria Johnson         
iResearch Atlanta, LLC Recruiting
Decatur, Georgia, United States, 30030
Contact: Monica Mahathre    404-537-1281    Monica.Mahathre@iResearchAtlanta.com   
iResearch Savannah Recruiting
Savannah, Georgia, United States, 31405
Contact: Casey Chacona       casey.chacona@iresearchsavannah.com   
Principal Investigator: Michael Mobley, MD         
United States, Maryland
CBH Health Recruiting
Gaithersburg, Maryland, United States, 20877
Contact: Evan Vance    301-251-4702    e.vance@cenexel.com   
Principal Investigator: Elia Acevedo, MD         
United States, Nebraska
Omaha Insomnia and Psychiatric Services Terminated
Omaha, Nebraska, United States, 68144
United States, Oregon
Peace Health Medical Group Recruiting
Eugene, Oregon, United States, 97401
Contact: Coleen Hudkins    458-205-7074    chudkins@peacehealth.or   
Principal Investigator: tom akins, MD         
United States, Texas
University of Texas Health Austin Recruiting
Austin, Texas, United States, 78712
Contact: jessica batten    512-495-5338    jessic.batten@austin.utexas.edu   
Principal Investigator: jorge almeida, md         
Roots Behavioral Health Recruiting
Austin, Texas, United States, 78746
Contact: Rachael Baker    512-707-1629    rachael@rootsbehavioralhealth.com   
Principal Investigator: Brent Turnipseed, MD         
JPS Health Terminated
Fort Worth, Texas, United States, 76104
Houston Mind and Brain Recruiting
Houston, Texas, United States, 77055
Contact: Cristina Rodriguez    832-699-7922    cristin.rodriguez@houstonmindandbrain.com   
Principal Investigator: Raymond Cho, MD         
Health Texas Recruiting
Richmond, Texas, United States, 77407
Contact: sara Khan    512-944-3771    sarak@perceptivepharmaresearch.com   
Principal Investigator: Aqeel Hashmi, MD         
Sponsors and Collaborators
NeuroRx, Inc.
Prevail Infoworks, Inc
Investigators
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Study Director: Martin Brecher, MD NRx Pharma
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Responsible Party: NeuroRx, Inc.
ClinicalTrials.gov Identifier: NCT03395392    
Other Study ID Numbers: NRX101-003
First Posted: January 10, 2018    Key Record Dates
Last Update Posted: October 5, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Bipolar Disorder
Suicidal Ideation
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Suicide
Self-Injurious Behavior
Lurasidone Hydrochloride
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
Dopamine Agents