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

The clinical trial is a Phase 2, double-blind, randomized, placebo controlled study in Major Depressive Disorder (MDD) participants currently treated with antidepressant therapy. The objective of the study is to assess CLE-100 for the treatment of MDD in participants currently treated with standard antidepressant therapy.

CLEO study is performed in two parts (part A and Part B). The sponsor is currently recruiting only for the Part B of the study.

Part A will be an inpatient study to assess the safety, tolerability, and pharmacokinetics of CLE-100 (oral esketamine) in MDD participants currently treated with an antidepressant drug. It will include a screening phase (up to 35 days), a 1 week inpatient double-blind treatment phase and an outpatient post treatment safety follow-up phase of 1 week after last study drug administration.

Part B will be a study to assess the safety and efficacy of CLE-100 (oral esketamine) in MDD participants currently treated with an antidepressant drug with inadequate response to standard antidepressant therapy.

The participants will remain on their current antidepressant therapy with no dose change during the study.

Eligibility Criteria:
Part A - Inclusion Criteria:

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

Part A - Exclusion Criteria:

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

Part B - Inclusion Criteria:

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

Part B - Exclusion Criteria:

1. Inadequate response to more than 5 treatment courses of antidepressant medication therapy during the current MDE
2. Current MDE for longer than 5 years.
3. 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.
4. Has a history or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorders.
5. Has dementia, delirium, amnesia, or any other significant cognitive disorder.
6. Has posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders, eating disorders, etc.).
7. Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk.
8. Has been randomized in Part A of this study.
9. Is a female of childbearing potential pregnant or breastfeeding.