NRX100 vs. Placebo for Rapid Stabilization of Acute Suicidal Ideation and Behavior in Bipolar Depression

NCT03396601 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: NRX100_001
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

NMDA antagonist drugs have increasingly been demonstrated to reduce symptoms of depression and suicidal ideation. NeuroRx has developed a sequential therapy consisting of IV NRX-100 (ketamine HCL) for rapid stabilization of symptoms of depression and suicidal ideation followed by oral NRX-101 (fixed dose combination of D-cycloserine and lurasidone) for maintenance of stabilization from symptoms of depression and suicidal ideation. This study will test the hypothesis that that NRX-100 is superior to placebo in achieving rapid reduction in symptoms of depression and suicidal ideation in patients with Severe Bipolar Depression and Acute Suicidal Ideation or Behavior within 24 hours of administration.

Conditions

Bipolar Depression; Suicidal Ideation

Outcome Measures

Primary Outcomes (1)

• Suicidal Ideation

  A score of 3 or less on the Columbia Suicidality Severity Rating Scale (C-SSRS). The scale is scored from 0 to 5 on suicidal ideation.

  24 hours

Secondary Outcomes (1)

• Depression

  24 hours

Study Arms (2)

NRX-100 infusion

EXPERIMENTAL

Infusion of IV NRX-100 (ketamine)

Drug: Ketamine Hydrochloride

Saline (placebo) infusion

EXPERIMENTAL

Infusion of IV Saline

Drug: Placebo

Interventions

Ketamine Hydrochloride DRUG

Ketamine HCl will be infused intravenously at a dose of 0.5 mg/kg over 40 minutes

NRX-100 infusion

Placebo DRUG

Normal Saline placebo will be infused IV over 40 minutes

Saline (placebo) infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 years of age, inclusive, at screening.
• Able to understand and provide written and dated informed consent prior to screening. Deemed likely to comply with study protocol and communicate AEs and other clinically important information, and agree to be hospitalized to complete screening and initiate experimental treatment.
• Resides in a stable living situation, in the opinion of the investigator
• Has an identified reliable informant, in the opinion of the investigator
• Diagnosed with bipolar disorder (BD) according to the criteria defined in the DSM-5. The diagnosis of BD will be made by a psychiatrist and supported by the MINI 7.0.2.
• Suicidal ideation or behavior as evidenced by an answer of "Yes" to item 4 or item 5 on the C-SSRS.
• A score of greater than or equal to 20 on the 10 items of the BISS that correspond with MADRS (equivalent to MADRS (BDM) total score of 30).
• In good general health, as ascertained by medical history, physical examination (including measurement of seated vital signs), clinical laboratory evaluations, and electrocardiogram
• If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:
• Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized \[status post hysterectomy, bilateral tubal ligation\], or post-menopausal with last menses at least one year prior to screening); or
• Childbearing potential, and meets the following criteria:
• i. Using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or sexually abstinent.
• ii. Negative urinary pregnancy test at screening, confirmed by a second negative urinary pregnancy test at randomization prior to receiving study treatment.
• iii. Willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence. The form of birth control will be documented at screening and pre-ketamine baseline.
• Body mass index between 18-35kg/m2.

You may not qualify if:

• Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
• Female who is pregnant or breastfeeding.
• Female with a positive pregnancy test at screening or before oral dosing of investigational product.
• Current DSM-5 diagnosis of moderate or severe substance use disorder (except marijuana or tobacco use disorder) within the 12 months prior to screening. Substance abuse cannot be the precipitant of entry to treatment.
• Subjects with a lifetime history of PCP/ketamine drug use, or failed use of ketamine for depression.
• History of schizophrenia or schizoaffective disorder, or any history of psychotic symptoms when not in an acute bipolar mood episode.
• History of anorexia nervosa, bulimia nervosa, or eating disorder NOS (OSFED) within five years of screening.
• Has dementia, delirium, amnestic, or any other cognitive disorder.
• Any major psychiatric disorder, including a personality disorder, which is clinically predominant to BD at screening, or has been the primary focus of treatment predominant to BD at any time within six months prior to screening.
• Current major psychiatric disorder, diagnosed at screening with the MINI 7.0.2, that is the primary focus of treatment, with BD as the secondary focus of treatment, within the past six months.
• A clinically significant abnormality on the screening physical examination that might affect safety or study participation, or that might confound interpretation of study results according to the study clinician.
• Current episode of:
• Hypertension, Stage 2, as defined by a systolic blood pressure ≥155 mmHg or diastolic blood pressure ≥99 mmHg within 1.5 hours prior to ketamine infusion on two of three measurements at least 15 minutes apart at the pre-ketamine assessment (on Day 0 at Visit 1).
• Recent myocardial infarction (within one year).
• Syncopal event within the past year.

Sponsors & Collaborators

• NeuroRx, Inc.: lead
• Target Health Inc.: collaborator

Study Sites (2)

Research Centers of America

Hollywood, Florida, 33024, United States

Location

JP Smith Hospital

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Suicidal Ideation

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Martin Brecher, MD

  VP, Clinical Development, NeuroRx, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and Care Providers will be masked with regard to medication administered. Outcomes Assessors will not be present during IV infusion of medication.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 11, 2018
• Study Start: June 25, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)