This study is about testing a new medicine, **CLE-100 (oral esketamine)**, to help people with Major Depressive Disorder (MDD). MDD is a serious condition where people feel very sad for a long time. In this study, participants will take either CLE-100 or a placebo (a pill that looks like the medicine but isn't) along with their current antidepressant. The study lasts for 4 weeks, and if you do well, you can continue with the medicine for another 6 months.

Key Points:

• The study involves taking a pill daily for 4 weeks, with possible extension to 6 months.
• You must have tried at least 2 different antidepressants without much success to join.
• Participants must be between 18-65 years old and should not have certain other medical conditions.

To join, you must be able to sign a consent form and have a history of not improving well on at least 2 antidepressants. This study is "double-blind," meaning neither you nor the doctors know if you're getting the real medicine or the placebo, which helps ensure unbiased results. If you have certain conditions like a history of substance abuse or other mental health disorders, you may not be eligible to participate.