nrx-101 for bipolar depression with subacute suicidal ideation

Conditions: Bipolar Depression; Suicidal Ideation and Behavior

Summary: nmda antagonist drugs have shown to reduce symptoms of depression and suicidal ideation. neurorx has developed nrx-101 (fixed dose combination of d-cycloserine and lurasidone) for oral use in the treatment of bipolar depression with suicidal ideation. this study will test the hypothesis that nrx-101 is superior to lurasidone alone (standard of care) in maintaining remission from symptoms of depression (primary endpoint) and suicidal ideation or behavior (declared secondary endpoint) over a six week period of twice-daily oral dosing.

background and rationale: nmda antagonist drugs have shown to reduce symptoms of depression and suicidal ideation. nrx-101 is composed of d-cycloserine (dcs) an nmda antagonist and lurasidone (5ht2a atypical antipsychotic and antidepressant). in a phase 2 clinical study of bipolar depression and acute suicidal ideation and behavior, (in patients requiring hospitalization) patients received an initial infusion of ketamine and then nrx-101 for 6 weeks. in that phase 2 study, nrx-101 showed the ability to maintain remission from depression and suicidality over 6 weeks when taken twice daily. in this current out patient study, patients with bipolar depression and subacute suicidality (not requiring hospitalization), ketamine will not be used. primary objective: * to test the hypothesis that treatment with nrx-101 is superior to standard of care (lurasidone) in improving symptoms of depression as measured by the total montgomery åsberg depression rating scale (madrs-10) score in patients with bipolar depression and subacute suicidal ideation and behavior (ssib) which does not require hospitalization. secondary objectives: • to test the hypothesis that treatment with nrx-101 is superior to standard of care (lurasidone) in reducing suicidality in depressed bipolar patients with ssib, as measured by the columbia suicide severity rating scale (c-ssrs) methodology: : a multi-center, randomized, double-blind, trial in which patients with bipolar depression (madrs ≥30) and subacute levels of suicidal ideation (c-ssrs 3 or 4, not requiring hospitalization) are randomized to receive twice daily oral nrx-101 or lurasidone (standard of care).

Eligibility criteria:
inclusion criteria: * diagnosed with bipolar disorder by a qualified rater according to the criteria defined in the diagnostic and statistical manual of mental disorders, fifth edition (dsm-5) and supported by the mini international neuropsychiatric interview (mini) 7.0.2. * confirmed active suicidal ideation (without the intention to act) as evidenced by an answer of 'yes' on item 3 and/or item 4 and not requiring hospitalization at screening and an answer of "no" on item 5 of the c-ssrs. * a total score greater than or equal to 30 on the 10 items of the madrs. * subject has no co-morbidities as ascertained by medical history, physical examination (including measurement of vital signs), clinical laboratory evaluations, and electrocardiogram (ecg) exclusion criteria: * subject has current dsm-5 diagnosis of moderate or severe substance use disorder (except marijuana or tobacco use disorder) within the 12 months prior to screening. * subject has a lifetime history of: * phencyclidine (pcp)/ketamine drug abuse, or * failed use of ketamine for depression or suicidality. * subject has schizophrenia or schizoaffective disorder, or any history of psychotic symptoms when not in an acute bipolar mood episode. * subject has a current major psychiatric disorder, diagnosed at screening * subject has been prescribed more than one agent in each of the following categories at randomization: * approved ssris * approved serotonin and norepinephrine reuptake inhibitors (snris) * approved tetracyclic antidepressants (tecas) * approved mood stabilizers (e.g., lithium, valproic acid, and lamotrigine) * subject has signs and symptoms of active or residual covid-19, or unresolved symptoms of covid-19 that impact health

Keywords: bipolar cyloserine lurasidone madrs cgi-ss c-ssrs