This study is testing a new medicine called CLE-100, also known as oral esketamine. It's for people with Major Depressive Disorder (MDD), which is a type of depression. This study is for adults aged 18-65 who have tried at least two other depression medicines but didn't get better. For the first 4 weeks, participants will take either CLE-100 or a placebo (a pill with no medicine) along with their current depression medicine. If they do well, they can join a 6-month extension where everyone gets CLE-100.

Key Points:

• Study Duration: 4 weeks, with an optional 6-month extension.
• Eligibility: Ages 18-65, diagnosed with MDD, and tried 2+ depression meds without success.
• Risks: Must not have certain medical conditions or a high risk of suicide.

Participants need to be able to read and sign a consent form. The study checks if CLE-100 works better than a placebo for people who haven't improved with other treatments. If interested, make sure you meet the criteria and understand the risks before joining.