A5343: A Trial of the Safety, Tolerability, and Pharmacokinetics of Bedaquiline and Delamanid, Alone and in Combination, among Participants Taking Multidrug Treatment for Drug-Resistant Pulmonary Tuberculosis

This is a randomized study, which means, by chance, you will be in one of three groups. You have an equal chance of being assigned to a group like flipping a coin. A5343 is an open label clinical trial, which means you will know which group you are in and what medications you will be taking.

This study will compare three treatment arms for people who have pulmonary multidrug resistant tuberculosis (MDR-TB). Pulmonary MDR-TB is a form of tuberculosis (TB) in the lung that is resistant to two or more of the primary drugs used for the treatment of TB (isoniazid and rifampin).

You will receive standard treatment for MDR-TB plus one or two new drugs for TB, called bedaquiline (BDQ) and delamanid (DLM). Throughout the study, you will be monitored to make sure that there are no safety concerns. Your heart will be monitored closely to make sure it is safe to give the drugs together.

This study looks at how the two new drugs fight MDR-TB when used alone with other TB drugs or used together. It looks at how the TB drugs work inside the body when you take them. It also looks at how safe and well tolerated these two drugs are in people.. Multiple times throughout the study, blood samples and an ECG, a test that measures the electrical activity in your heart, will be done to monitor the safety of the drugs.

Inclusion Criteria: To be in the study, you must:

• Be age 18 or older
• Have MDR-TB in your lungs and be on treatment less than 8 weeks
• Not be pregnant or breastfeeding
• Use an approved form of birth control for both men and women
• For persons with HIV : CD4 count above 100 cells/mm³ (CD4 cells are a kind of white blood cell that are a measure of the immune system)
• Taking treatment for MDR-TB before joining the study
• Willing to stay in hospital for at least 2 months
• Able to take pills by mouth
• Consent in writing to be in the study

Exclusion Criteria: You cannot be in the study if you:

• Have MDR-TB that does not involve the lungs
• Have received BDQ or DLM in the past
• Have any allergies to the study drugs
• Are actively drinking alcohol or using drugs
• Have heart problems or other serious illness
• Require or may require the use of certain drugs to treat HIV at the same time you are taking study drugs
• Require or may require the use of certain drugs, including, but not limited to, clofazimine and moxifloxacin, from 48 hours prior to study entry through 4 weeks after stopping study drugs

Up to 84 people will enroll in this study

The treatment arms are:

• Arm 1: BDQ (comes as a tablet to take by mouth)
• Arm 2: DLM (comes as a tablet to take by mouth)
• Arm 3: Both BDQ and DLM (as above)

The duration and doses will be explained by the study nurse or study doctor.

24 weeks on study treatment, followed by 104 weeks follow-up, for a total length of 128 weeks