Safety, Tolerability, PK Profile, and Symptom Response of a 7-Day Dosing With 25 mg or 50 mg Daily of REL-1017 in MDD

Inclusion Criteria

• Males between 18 and 65 years of age, inclusive; and females between 18 and 65 years of age, inclusive, who are >1 year postmenopausal.
• Diagnosed with recurrent MDD as defined by the Diagnostic and Statistical Manual, Fifth Edition (DSM-5), and confirmed by the Mini International Neuropsychiatric Interview, Version 7.0.2 (MINI).
• Diagnosed with a current MDE lasting 8 weeks to 36 months as defined by the DSM-5 and confirmed by the MINI.
• Treated with an adequate dosage of a SSRI, SNRI, or bupropion during the current MDE for at least 8 weeks prior to Screening with the same, adequate dosage for the last 4 weeks. Minimum adequate doses are defined in the (ATRQ). The maximum dose allowed for paroxetine is 40 mg QD, for fluoxetine is 60 mg QD, and for sertraline is 200 mg QD.
• Have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication in the current episode, as defined as 120 days in a 6-month period) up to 6 months prior to Screening or any recreational use of opioids.
• Evidence of clinically significant hepatic or renal impairment, including ALT or AST >1.5 x upper limit of normal (ULN), bilirubin >1 x ULN, or endocrine laboratory values (including clinically significant thyroid parameters, i.e., thyroid stimulating hormone [TSH], triiodothyronine [T3], and thyroxine [T4]).
• History or family history of sudden unexplained death or long QT syndrome (measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle).
• Any 12-lead ECG with repeated demonstration of QTc ≥450 msec or a QRS interval >120 msec at Screening.
• History of clinically diagnosed hypotension requiring treatment.
• History or presence of any condition in which an opioid is contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, bronchitis, or has/is suspected of having paralytic ileus).
• No more than 3 prescribed doses of an opioid within the 6 months prior to Screening and no use at all within the last month.
• Use of an antipsychotic, anticonvulsant, or mood stabilizer, regardless of indication, within the 3 months prior to Screening.
• History of allergy or hypersensitivity to methadone or related drugs (e.g., opioids).
• Positive test for hepatitis B or HIV. Patients with a positive hepatitis C test may be considered for inclusion with approval from the Medical Monitor.
• Any current and primary psychiatric disorder, as defined as a condition that is the primary focus of distress and/or treatment, other than MDD.
• Any lifetime history of bipolar I or II disorder, any psychotic disorder, post-traumatic stress disorder, borderline personality disorder, antisocial personality disorder, obsessive compulsive disorder, eating disorder, intellectual disability, or pervasive developmental disorder.
• History in the past 12 months of a primary diagnosis of anxiety disorder or panic disorder not related to the current MDE.
• Current diagnosis of alcohol or substance use disorder, as defined by DSM-5, at Screening or within the 12 months prior to Screening. Patients with the following diagnoses within the past 12 months, however, may be included at the Investigator's discretion: mild alcohol use disorder, mild cannabis use disorder, and any severity tobacco use disorder.
• A confirmed positive result on the urine drug/alcohol screen at Screening or Check-in. If the urine drug/alcohol screen is positive at Screening, retesting or rescreening may be scheduled with prior approval from the Medical Monitor.
• Patients who, in the Investigator's judgment, are at significant risk for suicide. A patient with a Columbia-Suicide Severity Rating Scale (C-SSRS) ideation score of 4 or 5 within the last 6 months or any suicide attempt within the past year must be excluded, as should a patient with an ideation score of 4 or 5 or any suicide attempt at the Check-in or Baseline Visi