NRX-101 for Maintenance of Remission From Severe Bipolar Depression in Patients With Suicidal Ideation (SBD-ASIB)
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|ClinicalTrials.gov Identifier: NCT03396068|
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : July 9, 2019
|Condition or disease||Intervention/treatment||Phase|
|Bipolar Depression Suicidal Ideation||Drug: NRX-101 Drug: Lurasidone HCl||Phase 2 Phase 3|
NeuroRx is developing NRX-101, a fixed-dose combination oral capsule composed of D-cycloserine (DCS) and lurasidone for the maintenance of remission from Severe Bipolar Depression with Acute Suicidal Ideation or Behavior (ASIB) in adults with Bipolar Depression following initial stabilization with ketamine. NRX-101 has been awarded Fast Track and Breakthrough Therapy Designation by the US Food and Drug Administration.
In recent years, intravenous and intranasal ketamine have demonstrated rapid and potent effects in achieving remission from both depression and suicidal ideation in both bipolar depression and major depressive disorder. However ketamine is will understood to induce hallucination and other dissociative side effects, to be addictive and have high abuse potential, and to have potential neurotoxic effects. Moreover, ketamine can only be administered in a monitored hospital or clinic setting. NRX-101 was developed with the objective of seeking a safe, non-hallucinogenic, non-addictive, oral medication that might maintain the effects of ketamine in patients with severe depression and acute suicidal ideation and which might be considered as initial therapy for patients with depression and non-acute suicidal ideation. The D-cycloserine component of NRX-101 is believed to act by inhibiting the brain's NMDA receptor and raising levels of glutamate/glutamine (Glx) in the anterior cingulate cortex. Increased Glx, as measured by magnetic resonance spectroscopy, has been associated with clinical improvement following electroconvulsive therapy (ECT) and following administration of IV ketamine.
To test the hypothesis that following successful response to a single infusion of ketamine (NRX-100), treatment with NRX-101 is superior to lurasidone in maintaining improvement in symptoms of depression as measured by the MADRS-10 total score.
Key secondary: To test the hypothesis that following response to a single infusion of NRX-100, daily oral NRX-101 is superior to lurasidone in delaying time to relapse of suicidality or depression in patients with Severe Bipolar Depression and Acute Suicidal Ideation and Behavior (ASIB). Avoiding relapse will be defined as being relapse-free, without experiencing a 50% or greater return to pre-infusion baseline levels of depression, or suicidality, or the need to implement a new treatment plan.
- To demonstrate that following NRX-100 response, treatment with NRX-101 are less likely to suffer from akathisia than those treated with lurasidone.
- To demonstrate that following NRX-100 response, other efficacy advantages observed in NRX-100 responders are more favorable for NRX-101 vs. lurasidone
- To demonstrate safety and tolerability of NRX-101 vs. lurasidone.
- To demonstrate that following successful NRX-100 response, NRX-101 diminishes the length of stay for index hospitalization vs. lurasidone.
Methodology: A multi-center, randomized, stratified, double-blind, adaptive trial conducted under a Special Protocol Agreement with the FDA that enrolls patients demonstrating successful response in NCT03396601. Randomization will be 2:1 favoring NRX-101 (n=48) vs. lurasidone alone (n=24).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Participants and Care Providers will be masked with regard to medication administered. Outcomes Assessors will not be present during IV infusion of medication.|
|Official Title:||NRX-101 for Maintenance of Remission From Severe Bipolar Depression in Patients With Acute Suicidal Ideation and Behavior: The SBD-ASIB Study|
|Actual Study Start Date :||June 25, 2019|
|Estimated Primary Completion Date :||September 30, 2020|
|Estimated Study Completion Date :||December 31, 2020|
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.
NRX-101, a fixed dose combination of D-cycloserine+lurasidone will be given twice a day by mouth
Other Name: Cyclurad
Active Comparator: Lurasidone 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
Lurasidone HCl will be given twice a day by mouth
- MADRS-10 [ Time Frame: Six weeks ]Difference in Montgomery Asberg Depression Rating Scale 10 Item Total Score between NRX-101 and lurasidone groups as measured by mixed model
- Time to Relapse (stage 2) [ Time Frame: 6 weeks ]Relapse is defined as a 50% or greater return to baseline level of depression, an increase in suicidality to C-SSRS 4 or higher, or the need to implement a new treatment plan.
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): NCT03396068
|Contact: Fred Grossman, DO||484-254-6134 ext firstname.lastname@example.org|
|United States, Alabama|
|Research Site, Birmingham||Not yet recruiting|
|Birmingham, Alabama, United States, 35294|
|United States, Florida|
|Research Site, Fort Lauderdale||Not yet recruiting|
|Fort Lauderdale, Florida, United States, 33024|
|United States, Texas|
|JP Smith Hospital||Recruiting|
|Fort Worth, Texas, United States, 76104|
|Contact: Alan Podawiltz, DO, MS, FAPA 817-702-3100 APodawil@JPSHealth.org|
|Contact: Cindy Claassen, PhD 817-702-5647 CClasse@JPSHealth.org|
|Research Site, Houston||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Study Director:||Fred Grossman, DO||Chief Medical Officer, NeuroRx, Inc.|