Adjunctive Oral KET-AD Capsules in Treatment Resistant Bipolar Depression

This study is testing a new oral ketamine treatment called KET-AD in adults with treatment-resistant bipolar depression (TRBD). The study will look at how safe and tolerable the treatment is, and whether it may help improve symptoms of depression when used together with a participant's usual treatment.

About 160 people will take part in the study. Participants will be randomly assigned (like flipping a coin) to receive either KET-AD or a placebo (a treatment with no active medicine). Neither the participant nor the study team will know which treatment the participant is receiving during the study.

The study treatment will be taken by mouth 3 times a week for up to 7 weeks. Participants will continue taking their usual standard treatment throughout the study.

The study has several parts:

Screening Period (up to 28 days)

Before joining the study, participants will complete tests and assessments to confirm whether they are eligible to take part.

Titration Phase (Weeks 1-3)

The first 3 weeks are used to find the highest dose of study treatment that each participant can comfortably tolerate.

All doses during this phase are given at the study clinic. Participants will start on a lower dose. Depending on how well the treatment is tolerated, the dose may be increased, kept the same, or reduced. The study doctor will carefully monitor participants for side effects after each dose.

Participants who cannot tolerate the treatment, or who cannot reach the required dose level by the end of Week 3, will stop study treatment and complete an early finish visit.

Maintenance Phase (Weeks 4-7)

Participants who tolerate the treatment during the Titration Phase may continue into the 4-week Maintenance Phase.

Participants will stay on the same dose throughout this phase. Some doses will still be given at the study clinic. Other doses may be taken at home if approved by the study doctor. Home doses will be supervised remotely by a mental health professional using a secure telehealth app.

Participants will use an electronic app during the study. The app will be used to complete questionnaires and other study assessments both at the clinic and at home. Participants may use their own device or be provided with one by the study team. Training will be provided before participants begin using the app independently.

Safety Monitoring

Participant safety will be closely monitored throughout the study by the study doctors and by an independent safety committee called a Data Safety Monitoring Board (DSMB).

Follow-up Visits

After treatment ends, participants will attend:

a follow-up clinic visit on Day 50, and an end-of-study visit on Day 64, which may be completed remotely.

Participants can leave the study at any time if they choose.