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NRX101 for Suicidal Treatment Resistant Bipolar Depression

Primary Purpose

Bipolar Depression, Suicidal Ideation and Behavior

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
NRX-101
Lurasidone HCl
Sponsored by
NeuroRx, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Depression

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Science 37Recruiting
  • San Marcus Research Clinic, Inc.Recruiting
  • ACMRRecruiting
  • iResearch Atlanta, LLCRecruiting
  • iResearch SavannahRecruiting
  • CBH HealthRecruiting
  • Omaha Insomnia and Psychiatric Services
  • Dent Neurologic InstituteRecruiting
  • Peace Health Medical GroupRecruiting
  • University of Texas Health AustinRecruiting
  • Roots Behavioral HealthRecruiting
  • JPS Health
  • Houston Mind and BrainRecruiting
  • Health TexasRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

NRX-101

Lurasidone

Arm Description

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

Following study enrollment, subjects will receive twice daily lurasidone

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mean Change from baseline in CGI-SS
Mean change from baseline to exit (Day 42/exit) in CGI-SS score
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)

Full Information

First Posted
January 4, 2018
Last Updated
March 24, 2023
Sponsor
NeuroRx, Inc.
Collaborators
Prevail Infoworks, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT03395392
Brief Title
NRX101 for Suicidal Treatment Resistant Bipolar Depression
Official Title
Comparison of NRX-101 to Standard of Care (Lurasidone) for Treatment-resistant Bipolar Depression With Suicidal Ideation and Behavior
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 12, 2022 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NeuroRx, Inc.
Collaborators
Prevail Infoworks, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Depression, Suicidal Ideation and Behavior

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants and Care Providers will be masked with regard to medication administered.
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NRX-101
Arm Type
Experimental
Arm Description
Following study enrollment and randomization, subjects will receive twice daily NRX-101
Arm Title
Lurasidone
Arm Type
Active Comparator
Arm Description
Following study enrollment, subjects will receive twice daily lurasidone
Intervention Type
Drug
Intervention Name(s)
NRX-101
Intervention Description
NRX-101, a fixed dose combination of D-cycloserine+lurasidone will be given twice a day by mouth
Intervention Type
Drug
Intervention Name(s)
Lurasidone HCl
Intervention Description
Lurasidone HCl will be given twice a day by mouth
Primary Outcome Measure Information:
Title
Change from Baseline in MADRS-10 over 42 Days
Description
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
Time Frame
Six weeks
Secondary Outcome Measure Information:
Title
Mean Change from baseline in CGI-SS
Description
Mean change from baseline to exit (Day 42/exit) in CGI-SS score
Time Frame
Six Weeks
Title
Time to Treatment Failure
Description
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)
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heather A Lothamer, RN, PhD
Phone
484-268-1654
Email
clinicaltrials@nrxpharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Marisa Gorovitz, MSW
Phone
484-268-1656
Email
mgorovitz@nrxpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Brecher, MD
Organizational Affiliation
NRx Pharma
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Andrew A Nierenberg, MD
Organizational Affiliation
Harvard Medical School (HMS and HSDM)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jonathan C Javitt, MD, MPH
Organizational Affiliation
NRx Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Science 37
City
Culver City
State/Province
California
ZIP/Postal Code
90320
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Selma Luedtke
Phone
206-512-4829
Email
selma.luedtke@science37.com
First Name & Middle Initial & Last Name & Degree
Christopher Reist, MD
Facility Name
San Marcus Research Clinic, Inc.
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
janeth bobadilla
Phone
305-424-7420
Email
jbobadilla@sanmarcusrc.com
First Name & Middle Initial & Last Name & Degree
nancy navarro gonzalez, MD
Facility Name
ACMR
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30331
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren White
Phone
404-881-5800
Email
l.white@cenexel.com
First Name & Middle Initial & Last Name & Degree
Maria Johnson
Facility Name
iResearch Atlanta, LLC
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monica Mahathre
Phone
404-537-1281
Email
Monica.Mahathre@iResearchAtlanta.com
Facility Name
iResearch Savannah
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31405
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Casey Chacona
Email
casey.chacona@iresearchsavannah.com
First Name & Middle Initial & Last Name & Degree
Michael Mobley, MD
Facility Name
CBH Health
City
Gaithersburg
State/Province
Maryland
ZIP/Postal Code
20877
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Evan Vance
Phone
301-251-4702
Email
e.vance@cenexel.com
First Name & Middle Initial & Last Name & Degree
Elia Acevedo, MD
Facility Name
Omaha Insomnia and Psychiatric Services
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68144
Country
United States
Individual Site Status
Terminated
Facility Name
Dent Neurologic Institute
City
Amherst
State/Province
New York
ZIP/Postal Code
14226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Violet wenner
Email
wenner@dentinstitute.com
First Name & Middle Initial & Last Name & Degree
Horatio Capote
Facility Name
Peace Health Medical Group
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Coleen Hudkins
Phone
458-205-7074
Email
chudkins@peacehealth.or
First Name & Middle Initial & Last Name & Degree
tom akins, MD
Facility Name
University of Texas Health Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78712
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jessica batten
Phone
512-495-5338
Email
jessic.batten@austin.utexas.edu
First Name & Middle Initial & Last Name & Degree
jorge almeida, md
Facility Name
Roots Behavioral Health
City
Austin
State/Province
Texas
ZIP/Postal Code
78746
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachael Baker
Phone
512-707-1629
Email
rachael@rootsbehavioralhealth.com
First Name & Middle Initial & Last Name & Degree
Brent Turnipseed, MD
Facility Name
JPS Health
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Individual Site Status
Terminated
Facility Name
Houston Mind and Brain
City
Houston
State/Province
Texas
ZIP/Postal Code
77055
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cristina Rodriguez
Phone
832-699-7922
Email
cristin.rodriguez@houstonmindandbrain.com
First Name & Middle Initial & Last Name & Degree
Raymond Cho, MD
Facility Name
Health Texas
City
Richmond
State/Province
Texas
ZIP/Postal Code
77407
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
sara Khan
Phone
512-944-3771
Email
sarak@perceptivepharmaresearch.com
First Name & Middle Initial & Last Name & Degree
Aqeel Hashmi, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be shared under an approved confidentiality agreement within one year of drug approval
IPD Sharing Time Frame
Within one year of drug approval
IPD Sharing URL
http://nrxpharma.com
Links:
URL
https://www.medrxiv.org/content/10.1101/2022.08.11.22278658v1.full
Description
STABIL-B Study Results

Learn more about this trial

NRX101 for Suicidal Treatment Resistant Bipolar Depression

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