NCT03396601

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

Administration of Intravenous NRX100 (Ketamine) vs Placebo Infusion for Rapid Stabilization of Acute Suicidal Ideation and Behavior in Patients With Bipolar Depression

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: NeuroRx, Inc. · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Background and Rationale: NMDA antagonist drugs have increasingly been demonstrated to reduce symptoms of depression and suicidal ideation. Specifically, NRX-100 (ketamine HCl, 0.5 mg/kg IV over 40 minutes) has been shown to induce acute reductions in suicidality and depression in patients with bipolar depression, relative to control. Numerous reports have documented a 50% reduction in the MADRS depression scale and a 75% reduction in suicidality following a single infusion of ketamine in patients with suicidal ideation and depression. While the repeat use of ketamine is not supported and may be contraindicated by the literature, D-cycloserine (DCS), when combined with SSRI antidepressants in patients with treatment resistant depression, and when combined with atypical antipsychotics, in particular lurasidone (NRX-101), has shown separation from control and ability to maintain remission from suicidality and depression over 6 weeks with oral use. Primary Objective: • To test the hypothesis that a single infusion of NRX-100 is superior to placebo infusion in the rapid stabilization of patients with severe Bipolar Depression and Acute Suicidal Ideation and Behavior (ASIB). Secondary Objectives: • Key secondary: To test the hypothesis that there is a more favorable reduction in the mean change from baseline on the Montgomery Asberg Depression Rating Scale (MADRS) between NRX-100 and saline groups on day 1 and day 2. Methodology: A multi-center, randomized, double-blind, trial involving a single IV infusion to achieve response by 24 hours. The randomization will be 3:1 favoring NRX-100 (ketamine) infusion (n=105) vs. Saline infusion (n=35). Subjects who respond successfully to treatment will be offered enrollment in a six week followup study of NRX-101 (an oral fixed dose combination of d-cycloserine and lurasidone) vs. standard of care in order to ascertain maintenance of the ketamine effect.

Conditions

• Bipolar Depression
• Suicidal Ideation

Interventions

Type	Name	Description
DRUG	Ketamine Hydrochloride	Ketamine HCl will be infused intravenously at a dose of 0.5 mg/kg over 40 minutes
DRUG	Placebo	Normal Saline placebo will be infused IV over 40 minutes

Timeline

• Start date: 2019-06-25
• Primary completion: 2024-12-31
• Completion: 2024-12-31
• First posted: 2018-01-11
• Last updated: 2024-01-19

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study