A Study of MI078 for Postpartum Depression

This study is designed as a multicenter, randomized, double-blind, placebo-controlled parallel-group trial. It plans to enroll two groups - one receiving the investigational drug and the other receiving placebo - with 100 participants per group. The study includes a screening period (Day -14 to Day -1), a treatment period (Days 1 to 4), and a follow-up period (Days 5 to 31). Eligible participants will be randomized in a 1:1 ratio and will take the study drug for a total of 3 days.

Inclusion criteria

• Female patients aged 18-45 years (inclusive) with a body mass index (BMI) of 18.5-37.0 kg/m² (inclusive).
• Based on the investigator's clinical evaluation, the participant meets the diagnostic criteria for Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by clinical assessment and the Mini-International Neuropsychiatric Interview (M.I.N.I.), with onset of depression between gestational week 28 and 4 weeks postpartum (inclusive).
• Within 12 months postpartum at baseline.
• Total score ≥26 on the 17-item Hamilton Depression Rating Scale (HAM-D17) at both screening and baseline.
• Understand and voluntarily participate in this trial, agree to comply with all study requirements, and provide written informed consent prior to any study-specific procedures.
• Able to communicate well with the investigator, willing and able to comply with lifestyle restrictions or requirements specified in the protocol, and capable of completing the trial as required.

Exclusion criteria

• Currently meeting diagnostic criteria for other DSM-5 psychiatric disorders, as assessed by the investigator.
• History of bipolar disorder, schizophrenia, and/or schizoaffective disorder.
• Reduction in HAM-D17 total score from screening to baseline ≥25%.
• Presence of suicidal ideation/intent, or HAM-D17 Item 3 (suicide) score >3, or a "yes" response to Item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) for suicidal ideation in the past 6 months at baseline, or a history of suicidal behavior within 1 year.
• Meeting diagnostic criteria for treatment-resistant depression.
• Continuous use of therapeutic doses of antidepressants for more than 14 days during the current episode.
• Discontinuation of psychotropic medications for less than 5 half-lives prior to the first dose of study drug.
• Need for concomitant use of other psychoactive drugs during the treatment period, including antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics (excluding non-benzodiazepines).
• Discontinuation of strong CYP3A4 inducers or inhibitors for less than 5 half-lives prior to the first dose of study drug.
• Receipt of systematic psychotherapy (e.g., interpersonal therapy, psychodynamic therapy, cognitive-behavioral therapy) or psychiatric-related acupuncture within 1 week prior to the first dose, or planned receipt of such treatments during the trial.
• Receipt of other physical treatments for psychiatric disorders (e.g., modified electroconvulsive therapy, transcranial magnetic stimulation, psychiatric-related laser therapy, vagus nerve stimulation, deep brain stimulation, light therapy) within 1 month prior to screening.
• Presence of severe or unstable cardiovascular, hepatic, renal, hematological, endocrine (e.g., uncontrolled hyper- or hypothyroidism), neurological (e.g., epilepsy, Parkinson's disease, multiple sclerosis, Huntington's disease, history of seizure disorder [except single febrile seizure in childhood]), gastrointestinal (e.g., history of gastrointestinal disease or surgery that may interfere with drug absorption, distribution, metabolism, or excretion), or other systemic or organ diseases, as judged by the investigator.
• History of malignancy within 1 year prior to screening.
• Participation in another drug trial within 3 months prior to screening, or participation in a medical device trial within 1 month prior to screening (defined as having received investigational drug or device treatment).
• Major surgery (excluding cesarean section) within 1 month prior to screening, or planned surgery during the trial period.
• History of hypersensitivity (allergy to at least 2 substances) or known allergy to progesterone.
• Positive pregnancy test at screening or baseline (for participants who are 4 weeks postpartum, a positive result requires retesting), or unwillingness to use effective contraception throughout the trial and for at least 3 months after the last dose of study drug, or plans for oocyte donation during this period.
• Clinically significant abnormal 12-lead electrocardiogram (ECG) or laboratory findings at screening or baseline that, in the investigator's opinion, may affect the trial, including but not limited to alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× upper limit of normal (ULN), or serum creatinine >1.5× ULN.
• Currently breastfeeding and unwilling to discontinue breastfeeding during the treatment period and for 7 days after the last dose.
• Any physical/psychological illness or condition that, in the investigator's opinion, may increase the risk of the trial, affect compliance with the protocol, or interfere with the completion of the study, or any other condition that the investigator deems unsuitable for participation in this trial.