A Study of CLE-100 (Oral Esketamine) in Addition to Standard Antidepressant Drug for Major Depressive Disorder - CLEO Study

Part A - Inclusion Criteria:

• Male or female between 18 to 60 years of age
• Primary diagnosis of MDD, without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
• MADRS score of at least 18 at Screening
• Treatment with stable dose of the current antidepressant therapy for at least 4 weeks for the current major depressive episode (MDE)
• Body mass index (BMI) between 18 and 40 kg/m2, inclusive
• Is able and competent to read and sign the informed consent form (ICF).

Part A - Exclusion Criteria:

• History of substance use disorder per DSM-5 criteria, except for tobacco use disorder
• History or current diagnosis of bipolar disorder, schizophrenia, schizoaffective disorders, binge eating disorder dementia, delirium, amnesia, or any other significant cognitive disorder
• Posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders)
• Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk
• Female of childbearing potential without appropriate contraceptive means, pregnant or breastfeeding

Part B - Inclusion Criteria:

• Male or female between 18 to 65 years of age
• Primary diagnosis of MDD without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
• MADRS score of at least 24 at Screening.
• At least 2 inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE)
• Current MDE for at least 12 weeks
• BMI between 18 and 40 kg/m2, inclusive.
• Is able and competent to read and sign the ICF.

Part B - Exclusion Criteria:

• Inadequate response to more than 5 treatment courses of antidepressant medication therapy during the current MDE
• Current MDE for longer than 5 years.
• 3. Has a current substance use disorder or history of any substance use disorder per DSM-5 criteria within 12 months prior to Screening, except for tobacco use disorder.
• Has a history or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorders.
• Has dementia, delirium, amnesia, or any other significant cognitive disorder.
• Has posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders, eating disorders, etc.).
• Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk.
• Has been randomized in Part A of this study.
• Is a female of childbearing potential pregnant or breastfeeding.