NRX-101 for Maintenance of Remission From Severe Bipolar Depression in Patients With Suicidal Ideation

NCT03396068 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: NRX101_002
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 4

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. NRX-101 has been awarded Fast Track and Breakthrough Therapy Designation by the US Food and Drug Administration. The SevereBD study will test the hypothesis that NRX-101 is superior to lurasidone alone in maintaining remission from symptoms of depression (primary endpoint), clinical relapse (declared secondary endpoint), and suicidal ideation or behavior (declared secondary endpoint) over a six week period of twice-daily oral dosing.

Conditions

Bipolar Depression; Suicidal Ideation

Outcome Measures

Primary Outcomes (1)

• MADRS-10

  Difference in Montgomery Asberg Depression Rating Scale 10 Item Total Score between NRX-101 and lurasidone groups as measured by mixed model

  Six weeks

Secondary Outcomes (1)

• Time to Relapse (stage 2)

  6 weeks

Study Arms (2)

NRX-101

EXPERIMENTAL

Subjects will be treated with oral NRX-101 (fixed dose combination of D-Cycloserine/lurasidone) that will be titrated to a combined dose of 950mg/66mg per day.

Drug: NRX-101

Lurasidone comparator

ACTIVE COMPARATOR

Subjects will be treated with oral lurasidone in a matched placebo capsule that will be titrated to a dose of 66 mg per day

Drug: Lurasidone HCl

Interventions

NRX-101 DRUG

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

Also known as: Cyclurad

NRX-101

Lurasidone HCl DRUG

Lurasidone HCl will be given twice a day by mouth

Lurasidone comparator

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.
• 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:
• a. 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 b. 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.
• Concurrent psychotherapy will be allowed if the type and frequency of the therapy (e.g., weekly or monthly) has been stable for at least three months prior to screening and is expected to remain stable for the duration of the study.
• Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, benzodiazepines, or trazodone) will be allowed if the therapy has been stable for at least four weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study. Subjects can also continue treatment with benzodiazepines used for anxiety if therapy has been stable for at least four weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study.

You may not qualify if:

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• 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).

Sponsors & Collaborators

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

Study Sites (4)

Research Site, Birmingham

Birmingham, Alabama, 35294, United States

Location

Research Centers of America

Hollywood, Florida, 33024, United States

Location

JP Smith Hospital

Fort Worth, Texas, 76104, United States

Location

Research Site, Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Suicidal Ideation

Interventions

Lurasidone Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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

Model Details: 2:1 randomization under FDA Special Protocol Agreement and Breakthrough Therapy Designation

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: January 10, 2018
• Study Start: December 1, 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 (4)