Population Pharmacokinetics and Pharmacodynamics of Standard First Line Anti-TB Versus Atorvastatin-Containing Regimens in the Treatment of Pulmonary Tuberculosis: A Sub-study of the ATORTUB Phase 2C Randomized Controlled Trial (ATORTUB popPK-PD Study)
The purpose of this study is to assess pharmacokinetic parameters of atorvastatin at different doses when combined with the standard first line tuberculosis (TB) treatment regimen in adults with drug sensitive pulmonary TB. The pharmacokinetics parameters will be correlated with Pharmcodynamic measures and a PK/PD model that will identify an optimal dosing regimen of atorvastatin that is appropriate for the treatment of pulmonary tuberculosis will be developed.
• Sputum specimen positive for tubercle bacilli on Gene Xpert or direct smear microscopy
• Either no previous anti-TB chemotherapy, or less than 2 weeks of previous chemotherapy
• Aged 12years and above
• A firm home address that is readily accessible for visiting
• Agreement to participate in the study and to give a sample of blood for HIV testing
• Normal baseline laboratory values at or within 14 days prior to screening:
‣ Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal
⁃ Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal
⁃ Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal
⁃ Serum or plasma potassium level greater than or equal to 3.5 meq/L
⁃ Hemoglobin level of 7.0 g/dL or greater
⁃ Platelet count of 100,000/mm3 or greater
• Informed consent to participate in the study and to give a sample of blood for HIV testing