A Study to Evaluate the Efficacy and Safety of SPT-300 (GlyphAllo) in Participants With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1 Study)

Inclusion criteria

• Participant is a male or female between 18 and 65 years of age, inclusive willing and able and have capacity to provide written informed consent.
• Participants must have a primary diagnosis of MDD. Participants with a diagnosis of comorbid generalized anxiety disorder, social anxiety disorder, or panic disorder (with or without agoraphobia) may be included if not the focus of treatment over the past 6 months prior to Screening and the Investigator considers MDD to be the primary diagnosis at Screening and Baseline.
• Eligible participants must have a current depressive episode of at least 4 weeks, but no greater than 18 months in duration prior to Screening.
• Women of childbearing potential (WOCP) must not plan to become pregnant during the course of the study or be currently breastfeeding. WOCP agree to use an acceptable form of highly effective contraception during participation in the study and for 30 days after receiving the last dose of study treatment.
• Body mass index (BMI) between 18 to 40 kg/m2, inclusive.
• Participant is willing and able to refrain from the use of drugs of abuse.

Exclusion criteria

• History of, or current presentation consistent with:

• any depressive episode with psychotic or catatonic features.
• any bipolar manic, hypomanic or mixed episode, and substance-induced (e.g., antidepressant-induced) manic, hypomanic/mixed episode.
• bipolar disorder, including history of bipolar depression, or current presentation consistent with bipolar depression.
• schizophrenia, schizoaffective, or other psychotic disorder.
• obsessive-compulsive disorder.
• any persistent neurocognitive disorder.
• History of treatment-resistant depression defined as 2 or more failed treatments of adequate dose and duration in the current depressive episode.
• Psychiatric hospitalization within current depressive episode.
• Evidence or history of clinically significant diseases which can affect the patients' participation.
• Previous history of intolerance or significant adverse effects, including drug allergy to allopregnanolone or any components of the SPT-300/placebo formulation.
• Participant has a history of drug or alcohol use disorder.
• Participants with a positive test for cannabinoids.
• Clinically significant risk of suicide or harm to self or others.