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Sequential Therapy for the Treatment of Severe Bipolar Depression. (STABIL-B)

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ClinicalTrials.gov Identifier: NCT02974010
Recruitment Status : Active, not recruiting
First Posted : November 28, 2016
Last Update Posted : August 27, 2018
Sponsor:
Collaborators:
Massachusetts General Hospital
Target Health Inc.
Information provided by (Responsible Party):
NeuroRx, Inc.

Brief Summary:
NeuroRx is developing NRX-101, a fixed-dose combination oral capsule composed of d-cycloserine (DCS) and lurasidone for the maintenance of remission from Acute Suicidal Ideation (C-SSRS level 4 or 5) and Behavior (ASIB) in adults with Bipolar Depression following initial stabilization. Patients with Bipolar Depression and ASIB will be recruited in both inpatient and outpatient settings and, following informed consent, will be given an intravenous infusion of ketamine 0.5mg/kg over 40 minutes. Those who exhibit a satisfactory clinical response to ketamine will be randomly allocated to NRX-101 or to a comparator group. The primary outcome variable is time to relapse as defined by a return to baseline in either depression or suicidality as determined by the treating physician or the need to institute a new treatment plan.

Condition or disease Intervention/treatment Phase
Bipolar Depression Suicidal Ideas Suicidal Ideation Suicide, Attempted Drug: NRX-101 Oral Capsule Drug: Lurasidone Oral Capsule Drug: Ketamine Intravenous Infusion Drug: Saline Solution Intravenous Infusion Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sequential Therapy (NRX-100 Followed by NRX-101) for the Treatment of Acute Suicidal Ideation and Behavior in Bipolar Depression: the STABIL-B Study
Actual Study Start Date : January 15, 2018
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Suicide

Arm Intervention/treatment
Experimental: NRX-101
NRX-101 is a fixed dose combination of d-cycloserine and lurasidone
Drug: NRX-101 Oral Capsule
Prospective Randomized Factorial Design Study as per arm/group descriptions
Other Name: D-cycloserine + Lurasidone Fixed Dose Combination

Drug: Ketamine Intravenous Infusion
Randomized administration of Ketamine or Placebo in a 3 to 1 ratio

Drug: Saline Solution Intravenous Infusion
Radomized administration of Ketamine or Placebo in a 3 to 1 ratio

Active Comparator: Lurasidone
Lurasidone will be administered in the same dosages as the lurasidone componenet of NRX-101
Drug: Lurasidone Oral Capsule
Prospective Randomized Factorial Design Study as per arm/group descriptions
Other Name: Lurasidone Fixed Dose Combination

Drug: Ketamine Intravenous Infusion
Randomized administration of Ketamine or Placebo in a 3 to 1 ratio

Drug: Saline Solution Intravenous Infusion
Radomized administration of Ketamine or Placebo in a 3 to 1 ratio




Primary Outcome Measures :
  1. Depression [ Time Frame: Six weeks ]
    The primary endpoint will be the mean change from baseline in BISS-derived MADRS score over treatment in support of improved symptoms of depression with NRX-101 relative to standard of care (lurasidone).


Secondary Outcome Measures :
  1. Relapse [ Time Frame: Six weeks ]
    The key secondary endpoint will be the time to relapse after initiation of treatment with study drug.



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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:A subject will be eligible for inclusion in this study only if all of the following criteria apply:

  1. Male or female, 18 to 65 years of age, inclusive, at screening.
  2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about AEs and other clinically important information.
  3. Diagnosed with Bipolar Disorder (BD) according to the criteria defined in the DSM-5. The diagnosis of BD will be made by a site psychiatrist and supported by the MINI 7.0.2. The diagnosis will be confirmed by remote, independent raters, via teleconference between the screen visit and the baseline visit.
  4. Suicidal ideation or behavior of sufficient severity to meet the requirements for a score of 4, or 5 on the C-SSRS (suicide attempt, interrupted attempt, aborted attempt, preparatory actions toward imminent suicidal behaviors, active method, intent +/- plan).
  5. A score equal to or greater than 20 on the MADRS items of the BISS.
  6. In good general health, in the opinion of the investigator, as ascertained by medical history, physical examination (PE) (including measurement of seated vital signs), clinical laboratory evaluations, and electrocardiogram (ECG).
  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 is post-menopausal with her last menses at least one year prior to screening); or

    • Childbearing potential, and meets the following criteria:

      • Childbearing potential, including women 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 is sexually abstinent.
      • Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at randomization prior to receiving study treatment.
      • 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 baseline.
  8. Body mass index between 18-35 kg/m2.
  9. Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive behavioral, insight-oriented) and frequency (e.g., weekly or monthly) of the therapy has been stable for at least three months prior to screening and if the type and frequency of the therapy is expected to remain stable during the course of the subject's participation in 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 4 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 sleep or anxiety if therapy has been stable for at least 4 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:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
  2. Female that is pregnant or breastfeeding.
  3. Female with a positive pregnancy test at screening or baseline.
  4. Current diagnosis of a substance use disorder (abuse or dependence, as defined by DSM-5, with the exception of nicotine dependence), at screening or within 6 months prior to screening.
  5. Current Axis I disorder, diagnosed at screening with the use of the MINI 7.0.2, that is the primary focus of treatment and BD the secondary focus of treatment for the past 6 months or more.
  6. History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms.
  7. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within 5 years of screening.
  8. Any Axis I or Axis II Disorder, which at screening is clinically predominant to their BD or has been predominant to their BD at any time within 6 months prior to screening.
  9. Has dementia, delirium, amnestic, or any other cognitive disorder.
  10. Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results according to the study clinician.
  11. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.
  12. Current episode of:

    • Hypertension, Stage 1 as defined by a systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg at screening on two of three measurements at least 15 minutes apart.
    • Hypertension, Stage 1 as defined by a systolic blood pressure ≥155 mmHg or diastolic blood pressure ≥99 mmHg at the Baseline Visit (Visit 1) within 1.5 hours prior to ketamine infusion on two of three measurements at least 15 minutes apart.
    • Recent myocardial infarction (within one year) or a history of myocardial infarction.
    • Syncopal event within the past year.
    • Congestive heart failure (CHF) New York Heart Association Criteria >Stage 2
    • Angina pectoris.
    • Heart rate <50 or >105 beats per minute at screening or randomization (Baseline Visit).
    • QTcF (Fridericia-corrected) ≥450 msec at screening or randomization (Baseline Visit).
  13. Current history of hypertension, or on antihypertensives for the purpose of lowering blood pressure, with either an increase in antihypertensive dose or increase in the number of antihypertensive drugs used to treat hypertension over the last 2 months.
  14. Chronic lung disease excluding asthma.
  15. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years.
  16. Presents with any of the following lab abnormalities:

    • Subjects with diabetes mellitus fulfilling any of the following criteria:

      • Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.5% at screening.
      • Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus-related illness in the past 12 weeks.
      • Not under physician care for diabetes mellitus.
      • Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 weeks.
    • Any other clinically significant abnormal laboratory result (determined as such by the investigator and medical monitor) at the time of the screening.
  17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
  18. Positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.
  19. Subjects with exclusionary laboratory values, or requiring treatment with exclusionary concomitant medications as defined in the study manual
  20. Subjects on exclusionary concomitant psychotropic medications.
  21. Subjects with a lifetime history of illicit PCP/ketamine drug use or previous failed use of ketamine for depression.
  22. Liver Function Tests higher than 2.5 times upper limit of normal as defined in the study manual.
  23. Known allergies to Lurasidone or Latuda, Cycloserine or Seromycin, Mannitol, Croscarmellose Sodium, Magnesium Stearate, Silicon Dioxide, and/or HPMC (hydroxypropylmethylcellulose)


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): NCT02974010


Locations
United States, Alabama
Research Site, Birmingham
Birmingham, Alabama, United States, 35294
United States, Florida
Research Site, Fort Lauderdale
Fort Lauderdale, Florida, United States, 33024
United States, North Carolina
Research Site, Charlotte
Charlotte, North Carolina, United States, 28211
United States, Texas
Research Site, Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
NeuroRx, Inc.
Massachusetts General Hospital
Target Health Inc.
Investigators
Principal Investigator: Andrew Nierenberg, MD Massachusetts General Hospital
Study Director: Daniel C Javitt, MD NeuroRx, Inc.

Responsible Party: NeuroRx, Inc.
ClinicalTrials.gov Identifier: NCT02974010     History of Changes
Other Study ID Numbers: NRX 101-001
First Posted: November 28, 2016    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NeuroRx, Inc.:
d-cycloserine
lurasidone
ketamine
randomized controlled trial

Additional relevant MeSH terms:
Depression
Depressive Disorder
Suicide
Bipolar Disorder
Suicidal Ideation
Suicide, Attempted
Behavioral Symptoms
Mood Disorders
Mental Disorders
Self-Injurious Behavior
Bipolar and Related Disorders
Ketamine
Lurasidone Hydrochloride
Cycloserine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents