Zelquistinel in the Treatment of Major Depressive Disorder

Inclusion Criteria: * Written informed consent from the participant has been obtained prior to any study -related procedures (as described in Appendix 3). * Male or female participants must be 18 to 65 years of age, inclusive, at the time of signing the informed consent. * Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for MDD (based on confirmation from the modified Structured Clinical Interview for DSM disorders \[SCID\]), with a current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1. * Have a minimum score of 26 on the rater-administered Montgomery-Asberg depression rating scale (MADRS) and a minimum score of 24 on the computer-administered MADRS at both Visit 1 (Screening) and Visit 2 (Baseline). * Have a difference of no greater than 7 points between the rater-administered MADRS and computer-administered MADRS at both Visit 1 (Screening) and Visit 2 (Baseline). * Have a clinical global impression-severity (CGI-S) score ≥ 4 at both Visit 1 (Screening) and Visit 2 (Baseline). * Have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test if a woman of childbearing potential (WOCBP). * Female participants willing to minimize the risk of becoming pregnancy for the duration of the clinical study and follow-up period. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * not a WOCBP OR * A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 of protocol during the treatment period and for at least 5 terminal half-lives after the last dose of study treatment. * Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 5 terminal half-lives after the last dose of study treatment and refrain from donating sperm during this period. * Able, as assessed by the investigator, and willing to follow study instructions and likely to complete all required study visits. * Normal physical-examination findings, clinical-laboratory test results, and electrocardiogram (ECG) results from Visit 1 (Screening) or abnormal results that are determined to be not clinically significant by the investigator. * Body mass index (BMI) within the range 18 and 40 kg/m\^2 (inclusive). * Eligibility confirmed through a formal adjudication process (see Section 9 Diagnostic Assessments). Exclusion Criteria: Psychiatric and Treatment-Related Criteria * DSM-5-based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1. Comorbid generalized anxiety disorder, social anxiety disorder, or specific phobias are acceptable provided they play a secondary role in the balance of symptoms and are not the primary driver of treatment decisions. * Lifetime history of meeting DSM-5 criteria for: * Schizophrenia spectrum or other psychotic disorder * Bipolar or related disorder * Major neurocognitive disorder * Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study * Dissociative disorder * Posttraumatic stress disorder * MDD with psychotic features * History of meeting DSM-5 criteria for alcohol or substance use disorder (other than nicotine or caffeine) within the 6 months before Visit 1. * DSM-5-based diagnosis of any personality disorder of sufficient severity to interfere with participation in this study in the opinion of the investigator. * History (based on participant report and/or medical records, and investigator judgment) of: * Inadequate response to electroconvulsive therapy (ECT), a monoamine oxidase inhibitor, ketamine, or adjunctive treatment with an antipsychotic * Treatment with clozapine or any depot antipsychotic * ECT, vagus nerve stimulation, transcranial magnetic stimulation, or any experimental central nervous system treatment during the current episode or in the 6 months before Visit 1 (whichever is longer) * Tardive dyskinesia, serotonin syndrome, or neuroleptic malignant syndrome * Having received: * Anticonvulsant/mood stabilizer, within 1 year prior to Visit 1 * Antipsychotic in the current episode, with the exception of quetiapine given for insomnia ≤ 50 mg/day provided it can be safely discontinued prior to Visit 2 * Combination therapy of 2 or more antidepressant therapies (ADTs) in the current episode if given for depression at adequate dose and duration * ADT augmentation agent in the current episode * Lifetime history of nonresponse to ≥ 2 antidepressants after adequate trials (adequate treatment is defined as at least 6 weeks at an adequate dose(s) based on approved package insert recommendations) or a non-response to an antidepressant after adequate treatment for the current major depressive episode. * Positive result at Visit 1 from the urine drug screen (UDS) test for any prohibited medication. Exception: participants with a positive UDS at Visit 1 for opiates, cannabinoids, or episodic use of benzodiazepines may be allowed in the study provided: * The drug was used for a legitimate medical purpose; * The drug can be discontinued prior to participation in the study (except for episodic use of benzodiazepines which may be continued); and * A repeat UDS is negative for these substances prior to enrollment (except for episodic use of benzodiazepines which may be continued) * Suicide risk, as determined by meeting any of the following criteria: * A suicide attempt within the past year * Significant risk, as judged by the investigator, based on the psychiatric interview or information collected in the C-SSRS at Visit 1 (Screening) or Visit 2 (Baseline) * MADRS Item 10 score ≥ 5 at Visit 1 (Scr…

Reproduced word-for-word from the public registry record — the study team can answer questions about it.