ATORvastatin in Pulmonary TUBerculosis: a POPulation PharmacoKinetics -PharmacoDynamics Sub-study (ATORTUB popPK-PD)

Prior treatment

• Participants known or suspected of having any form of drug resistance TB.
• Currently on anti TB medication
• alcoholic beverages, food or drinks containing methyl- xanthine (i.e. energy drinks, tea leaves, coffee beans, cocoa, kola nuts, medications e.g. theophylline). Ingestion of grapefruit/ products containing grapefruit juice, bitter oranges, garlic supplements, St John's Wort or other herbal supplements, within 7 days prior to the first treatment and throughout the study will not be allowed.

Other illness

• Patients co infected with HIV
• Those with poor general condition where no delay in treatment can be tolerated
• Evidence of clinically significant metabolic or co morbid medical conditions ; malignancy; or other diseases like history of or current cardiovascular disorder such as heart failure, coronary heart disease, arrhythmia.
• Known or family history of bleeding disorders.
• Presence of any of the pre-existing non-TB diseases outlined in the protocol
• Diabetes mellitus
• Hypertension
• Any other chronic illness/ co morbidities that warrants being on daily routine medications
• Presence of a psychiatric illness

Lab values

• Any renal impairment characterized by serum creatinine clearance of 1.5 x upper limit of normal of the clinical laboratory reference range at screening.
• Myositis and or Creatinine phosphokinase three times upper limit of normal

Other

• Patient in a moribund state
• Has TB meningitis
• pregnant, or breast feeding mothers
• Current Tobacco Smokers/ tobacco use in any form
• Alcoholism
• Individuals that are enrolled in other therapeutic clinical trials

• 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