The three-part study, which will last up to 62 weeks, will compare the effectiveness of the active investigational medicine with a placebo, a substance that has no therapeutic effect, given with psychological support. 

Two-thirds of the people in Parts A and B will receive the active investigational medicine and one third will receive placebo. If you join the study, in Part A and B neither you nor your study doctors will know which study treatment you are going to receive because the decision is made randomly by a computer and not revealed to anyone. Part C is open label so if you are eligible for treatment, you will receive the active investigational product.

The aim of the study is to assess the efficacy and safety of the investigational medication versus placebo for reducing symptom severity in TRD, when administered with psychological support. This will be assessed in a 6-week, single-dose, double-blind, placebo-controlled part of the study (Part A). Durability of efficacy and long-term safety, and the efficacy and safety of re-treatment will be assessed in a 20-week single-dose, double-blind re-treatment part (Part B), and a 26-week open-label treatment part (Part C). As TRD is a chronic condition with frequent relapse common, this three-part study allows for important long-term monitoring.

Participants will receive support from study clinicians to help them taper off any prohibited medications, including current antidepressants. Participants will be asked to remain off prohibited medications for the parts of the study under close medical supervision. Reimbursement for reasonable, out-of-pocket expenses for travel and other expenses may be available to qualified individuals.