Clinical TrialBipolar DisorderPlaceboUnknown status

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

The SevereBD study will test the hypothesis that NRX-101 is superior to lurasidone alone in maintaining remission from symptoms of depression, clinical relapse, and suicidal ideation/behavior over a six-week period of twice-daily oral dosing in patients stabilized with ketamine (n=72; 2:1 randomization).

Target Enrollment
72 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind

Detailed Description

This multi-centre, randomized, stratified, double-blind, parallel-group Phase III trial evaluates oral NRX-101 (fixed-dose D‑cycloserine + lurasidone) versus lurasidone alone for maintenance of remission in adults with severe bipolar depression and acute suicidal ideation/behavior after initial stabilization with an IV ketamine infusion.

Primary endpoint is maintenance of improvement on MADRS-10; key secondary endpoints include time to relapse of suicidality or depression and safety/tolerability measures. Randomization is 2:1 favoring NRX-101 with titration to target daily doses (DCS 950 mg + lurasidone 66 mg) administered twice daily for six weeks.

Study Arms & Interventions

NRX-101

experimental

Oral fixed-dose combination of D-cycloserine + lurasidone titrated to target daily dose; given twice daily for maintenance after ketamine stabilization.

Interventions

  • Compound950 mg
    via Oral• twice daily

    Combined D-cycloserine 950 mg/day + lurasidone 66 mg/day (NRX-101), titrated to target; total daily combined dose reported.

Lurasidone

active comparator

Matched capsule containing lurasidone titrated to 66 mg/day (active comparator).

Interventions

  • Placebo66 mg
    via Oral• twice daily

    Lurasidone 66 mg/day (titrated); comparator encoded as placeholder compound and dose described here.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • A subject will be eligible for inclusion in this study based on successful response to infusion under NCT03396601 and the following criteria:
  • 1. 18 to 65 years of age, inclusive, at screening.
  • 2. 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.
  • 3. Resides in a stable living situation, in the opinion of the investigator
  • 4. Has an identified reliable informant, in the opinion of the investigator
  • 5. 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.
  • 6. In good general health, as ascertained by medical history, physical examination (including measurement of seated vital signs), clinical laboratory evaluations, and electrocardiogram
  • 7. 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.
  • 8. Body mass index between 18-35kg/m2.
  • 9. 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.
  • 10. 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.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
  • 2. Female who is pregnant or breastfeeding.
  • 3. Female with a positive pregnancy test at screening or before oral dosing of investigational product.
  • 4. 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.
  • 5. Subjects with a lifetime history of PCP/ketamine drug use, or failed use of ketamine for depression.
  • 6. History of schizophrenia or schizoaffective disorder, or any history of psychotic symptoms when not in an acute bipolar mood episode.
  • 7. History of anorexia nervosa, bulimia nervosa, or eating disorder NOS (OSFED) within five years of screening.
  • 8. Has dementia, delirium, amnestic, or any other cognitive disorder.
  • 9. 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.
  • 10. 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.
  • 11. 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.
  • 12. Current episode of untreated hypertension, recent MI, syncopal event, CHF NYHA >Stage 2, angina, HR <50 or >105, or QTcF ≥450 ms (men) / ≥470 ms (women) on two of three measurements at specified times.
  • 13. History of hypertension managed with recent medication changes.
  • 14. Chronic lung disease, excluding asthma.
  • 15. Lifetime history of neurosurgery, encephalitis/meningitis, degenerative CNS disorder, epilepsy, intellectual disability, or recent significant head trauma.
  • 16. Significant lab abnormalities (including unstable diabetes as defined in protocol).
  • 17. Any current or past physical condition that might put the subject at risk or interfere with study results.
  • 18. Subjects on exclusionary concomitant psychotropic medications as defined in the protocol.
  • 19. At randomization, subjects prescribed more than one agent in each prohibited category (e.g., certain antidepressants, mood stabilizers).
  • 20. Subjects with exclusionary laboratory values.
  • 21. Known allergies to lurasidone, cycloserine, or specified excipients.
  • 22. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.
  • 23. Study site personnel or immediate family members of such personnel.

Study Details

  • Status
    Unknown status
  • Phase
    Phase III
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment72 participants
  • Timeline
    Start: 2019-12-01
    End: 2022-04-30
  • Compound
    Placebo
  • Topic
    Bipolar Disorder

Locations

Research Site, Birmingham — Birmingham, Alabama, United States
Research Centers of America — Hollywood, Florida, United States
JP Smith Hospital — Fort Worth, Texas, United States
Research Site, Houston — Houston, Texas, United States

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