BPL-003 Efficacy and Safety in Treatment Resistant Depression

Approximately 200 eligible participants will receive a single dose of either low, medium, or high doses of BPL-003, given intranasally, with 8 weeks of follow up assessments. Following this participants may receive a second dose of either monophasic or biphasic dose of BPL-003, given intranasally, with another 8 weeks of follow up assessments.

Psychological support will be given before, during and after each dosing.

Inclusion criteria

• At least moderate major depressive disorder.
• Diagnosed with TRD defined as failure to respond to an adequate dose and duration of at least 2 pharmacological treatments based on the MGH ATRQ assessment.
• Hamilton Depression Rating Scale score ≥19 at Screening and Baseline.
• CGI-S ≥4 at Screening and Baseline.
• If currently taking antidepressant medications, willing and able to discontinue current antidepressants.

Exclusion criteria

• Current or past history of schizophrenia, psychotic disorder including psychotic depression, bipolar disorder, delusional disorder, schizoaffective disorder, or any other severe psychiatric disorder.
• Current personality disorders.
• First-degree family history of schizophrenia, bipolar disorder, delusional disorder, or schizoaffective disorder.
• Current alcohol or substance use disorder (other than caffeine or nicotine).
• A participant who at any time has been unresponsive to ketamine, esketamine, an adequate course of treatment with electroconvulsive therapy, or has received vagal nerve stimulation or deep brain stimulation.
• Suicidal ideation or behavior within the 12 months prior to the start of Screening or on Day 1 prior to dosing.
• Suicide attempt and/or self-injurious behavior within the last 12 months prior to Screening.
• Uncontrolled medical conditions e.g. hypo/hyperthyroidism, diabetes, renal failure.
• History or current uncontrolled hypertension.
• Seizure disorder or any seizure in the 2 years prior to Screening.
• Has clinically significant results on ECG during the Screening.
• Any nasal obstruction, blockage, or symptoms of congestion at the time of dosing that in the investigator's opinion may interfere with the administration of the study medication.
• Female participants who are pregnant, lactating, or of childbearing potential and not willing to use adequate forms of contraception during the study.
• Male participants who are sexually active and not willing to use adequate forms of contraception during the study.