A5312: The Early Bactericidal Activity of High Dose or Standard Dose Isoniazid among adult Participants with Isoniazid-Resistant or Drug Sensitive Tuberculosis

This study is for participants who have pulmonary tuberculosis (TB), a bacterial infection in their lungs. Isoniazid (INH) is a drug commonly used to treat TB. Sometimes, the bacteria that cause TB can become resistant to INH, and then INH does not work as well at fighting the bacteria. This study will treat people with INH-resistant TB with different doses of INH to see if INH can still fight the bacteria if we just increase the dose.

We will compare how well the drug works at higher doses for participants who have resistant TB to how well the drug works at regular doses for participants who have TB that is sensitive to the drug. The study will also compare the safety and tolerability of the different doses of INH.

Inclusion Criteria:

• New or current pulmonary TB
• Adults between the ages of 18 and 65

Exclusion Criteria

• Known exposure to extensively resistant TB (XDR-TB)

Total number of participants: Between 128 and 218

If you join this study, you will need to be admitted to the hospital for at least 9 days. If you have not stopped taking INH you may need to be admitted for longer (up to 16 days in total) so that there is time for the INH to wash out of your body. While you are in the hospital, you will be asked to collect the sputum that you cough up in a container. Seeing how many bacteria are in the sputum you cough up will help us to know how well the medicine is working. After you are discharged from the hospital, you will come to the clinic 14 days later for a final visit.

If you meet the eligibility requirements for the study, you will have a test to see if you have INH-resistant TB, and if it is low-level or high-level resistance. (With low-level resistance, the bacteria are not as resistant to INH as they are with high-level resistance.) You may also be asked to provide sputum for other types of resistance tests.

Depending on the test result, you will be assigned to one of 3 groups:

• If you have low-level INH resistance, you will either be referred to receive standard TB treatment outside of the study or be randomized (like a flip of a coin) to receive 5, 10 or 15 mg/kg INH once a day for 7 days. Randomized means that you have equal chance of being in any of these 3 groups. (Mg/kg, or milligrams per kilogram, means the amount of INH in milligrams you will receive for each kilogram you weigh.)
• If your test shows no INH resistance, you will either be referred to receive standard TB treatment outside the study or you will receive 5 mg/kg INH once a day for 7 days.
• If you have high-level resistance, you will either be referred to received standard TB treatment outside the study or you will be randomized to receive 15 or 20 mg/kg INH once a day for 7 days.

INH will be provided for you. In addition, you must also take vitamin B₆ once a day while taking INH, to help prevent possible side effects of INH. Vitamin B₆ will also be provided to you. When you are finished taking study drug, you will be referred for full TB treatment outside the study.

About 23 days