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NRX-101

Phase 2

Bipolar Depression | Small molecule | Psychiatry |NRX Pharmaceuticals, Inc.|Last Updated: Jun 24, 2026

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMC
Total Trials3
Total Enrollment104

FDA Designations

BREAKTHROUGH_THERAPY

Clinical trial landscape

NRX-101 · 4 trials · 7 indications

Phase 2 4
NCT07227103A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Robotic Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS TrialTreatment Resistant Depression
NOT YET_RECRUITING400 Analytics
NCT03395392NRX-101 for Bipolar Depression With Subacute Suicidal IdeationBipolar Depression
COMPLETED74 Analytics
NCT03402152NRX101 Glx Biomarker Validation StudyBipolar Depression
COMPLETED8 Analytics
NCT02974010Sequential Therapy for the Treatment of Severe Bipolar Depression.Bipolar Depression
COMPLETED22 Analytics
PHASE2NOT YET_RECRUITING
A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Robotic Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS Trial
Treatment Resistant DepressionUnlock trial analytics
PHASE2COMPLETED
NRX-101 for Bipolar Depression With Subacute Suicidal Ideation
Bipolar DepressionUnlock trial analytics
PHASE2COMPLETED
NRX101 Glx Biomarker Validation Study
Bipolar DepressionUnlock trial analytics
PHASE2COMPLETED
Sequential Therapy for the Treatment of Severe Bipolar Depression.
Bipolar DepressionUnlock trial analytics

Study Endpoints

Primary Endpoints

MADRS Depression
6 weeks

Montgomery Asberg Depression Rating Scale Total Score

CGI-SS Suicidality
6 weeks

Clinical Global Impression Suicidality Scale

Change from Baseline in MADRS-10 over 42 Days
Six weeks

Mean change from baseline to endpoint (Day 42/exit) in total MADRS score, a 10-item clinician-rated scale, with each item rated on a 0-6 severity scale (0 Minimum, 60 maximum), where higher scores indicate a worse outcome

Glx
Immediate

Mean change in Glx Area Under the Curve (AUC) measured in 15 minute increments over 2 hours at following experimental drug vs. comparator

BDM Score (BISS-derived MADRS) Change From Baseline at Day 42
Day 42

The study will measure the difference on BISS-derived MADRS score between NRX-101 and lurasidone (comparator) groups. The Bipolar Inventory of Symptom Scale (BISS) is a validated 42-item clinician-rated scale (21 items each for the depression and mania subscales) in which each item is rated on a 0-4 severity scale where higher values indicate worse severity. BISS-derived MADRS (BDM): MADRS is a 10-item clinician-rated scale, with each item rated on a 0-6 severity scale, where a higher number indicates worse severity. Responses to each question are equally weighted and summed. The BDM has a minimum score of 0 and a maximum of 40, where higher scores indicate a worse severity, therefore decreases in average BDM are considered a better outcome. Data are presented as mean change from baseline (end of stage 1, Day 1) using LOCF

Secondary Endpoints

EMOCARE Depression Thermometer
6 weeks
Percent Response on MADRS
Six weeks
Percent Remission from Depression on MADRS
Six weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Transcranial Magnetic Stimulation plus NRX-101EXPERIMENTALParticipants are treated with ONE-D TMS plus NRX-101 175mg DCS/8.5mg Lurasidone once daily for five days
Transcranial Magnetic StimualtionPLACEBO_COMPARATORParticipants are treated with ONE-D TMS plus placebo once daily for five days
Sham TMS + NRX-101EXPERIMENTALParticipants will be treated with Sham TMS (i.e. a TMS coil that does not deliver effective energy to the brain) + NRX-101
NRX-101EXPERIMENTALFollowing study enrollment and randomization, subjects will receive twice daily NRX-101
LurasidoneACTIVE_COMPARATORFollowing study enrollment, subjects will receive twice daily lurasidone
NRX-101 vs. PlaceboEXPERIMENTALFollowing study enrollment and randomization, subjects will undergo two treatment sessions, 3 days apart. Each treatment session will be conducted while the subject is undergoing Magnetic Resonance Spectroscopy to measure Glx in the ACC. In one treatment session the subject will receive oral placebo and in the other treatment session the subject will receive oral NRX-101. Following the second treatment session, the subject will participate in a four week open study of NRX-101, at the end of which a third session of Magnetic Resonance Spectroscopy will be conducted.
NRX-101 vs. lurasidone HClEXPERIMENTALFollowing study enrollment and randomization, subjects will undergo two treatment sessions, 3 days apart. Each treatment session will be conducted while the subject is undergoing Magnetic Resonance Spectroscopy to measure Glx in the ACC. In one treatment session the subject will receive oral lurasidone and in the other treatment session the subject will receive oral NRX-101. Following the second treatment session, the subject will participate in a four week open study of NRX-101, at the end of which a third session of Magnetic Resonance Spectroscopy will be conducted.

Interventions

NameTypeDescription
Neuronavigated robotic-enabled TMSDEVICEOne Day TMS Protocol performed with the Zeta Surgical neuronavigated robotic-enabled system and the neurocare Apollo TMS Device 30 Theta burst pulses delivered as per protocol
NRX-101DRUGD-cycloserine 175mg + Lurasidone 8.5mg
Sham TMSDEVICEAn Apollo TMS device configured not to deliver effective energy to the brain
Oral PlaceboDRUGAn oral placebo capsule visually identical to NRX-101
Lurasidone HClDRUGLurasidone HCl will be given twice a day by mouth
PlaceboDRUGPlacebo oral capsule
NRX-101 Oral CapsuleDRUGProspective Randomized Factorial Design Study as per arm/group descriptions
Lurasidone Oral CapsuleDRUGProspective Randomized Factorial Design Study as per arm/group descriptions
Ketamine Intravenous InfusionDRUGRandomized administration of Ketamine or Placebo in a 3 to 1 ratio
Saline Solution Intravenous InfusionDRUGRandomized administration of Ketamine or Placebo in a 3 to 1 ratio
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Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites3

18 to 65 years of age, inclusive, at Screening. 2. Participants must be initiating a new course of TMS treatment and must be TMS-naïve. 3. Able to understand and provide written and dated informed consent prior to Screening. 4. Deemed likely to comply with the study protocol, including communication...

Countries:United States
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Frequently asked questions about NRX-101

What is NRX-101 used for?

NRX-101 is an investigational small molecule being developed for treatment resistant depression and bipolar depression. It is currently in Phase 2 clinical development and has been studied in patients with bipolar depression with suicidal ideation. The drug is being evaluated for its ability to treat these psychiatric conditions.

Who makes NRX-101?

NRX-101 is being developed by NRX Pharmaceuticals, Inc., a biopharmaceutical company traded on the Nasdaq under the ticker symbol NRXP. The company is conducting clinical trials of NRX-101 in the United States for psychiatric indications including bipolar depression and treatment resistant depression.

What phase is NRX-101 in?

NRX-101 is in Phase 2 clinical development. It has received Breakthrough Therapy designation from the FDA. The drug is investigational and has not been approved by the FDA. Multiple Phase 2 trials have been completed, and an additional Phase 2 trial is planned but has not yet begun recruiting patients.

What clinical trials is NRX-101 in?

NRX-101 has been studied in several clinical trials. Completed Phase 2 trials include NCT02974010 for severe bipolar depression, NCT03395392 for bipolar depression with subacute suicidal ideation, and NCT03402152, a biomarker validation study. A new Phase 2 trial, NCT07227103, is planned for treatment resistant depression using robotic transcranial magnetic stimulation.

Is NRX-101 the same as other names?

NRX-101 is the primary name used for this investigational drug in clinical trials and by its developer, NRX Pharmaceuticals. No alternative names have been reported for this compound in the available clinical trial information.

How does NRX-101 work?

NRX-101 is a small molecule being studied for its effects on depression. The specific molecular target of NRX-101 has not been disclosed in the available information. Clinical trials are evaluating its efficacy in treating bipolar depression and treatment resistant depression, including in patients with suicidal ideation.