Study of Daily Rifapentine for Pulmonary Tuberculosis
Condition: Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Intervention: Rifapentine 450; Rifapentine 600; Rifampin
Intervention description: rifapentine 450 mg; rifapentine 600 mg; rifampin 600 mg
Intervention MeSH terms: Rifampin; Rifapentine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 153.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tuberculosis; Pharmacokinetics

Summary:

      The goal of this Phase 2 study is to determine the microbiological activity and safety of
      rifapentine when given as a component of multidrug intensive phase treatment of
      smear-positive pulmonary tuberculosis (TB).

      Funding Source- FDA Office of Orphan Products Development (OOPD)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of
             expectorated sputum. Patients having extra-pulmonary manifestations of tuberculosis,
             in addition to smear-positive pulmonary disease, are eligible for enrollment.

          2. No prior history of tuberculosis disease or tuberculosis treatment

          3. No treatment with fluoroquinolones in the 2 months preceding initiation of study
             drugs.

          4. Age > 18 years

          5. Weight ≥ 50 kg and ≤ 80 kg

          6. Karnofsky score of at least 60 (requires occasional assistance but is able to care for
             most of his/her needs; see Appendix)

          7. Signed informed consent

          8. Ability to adhere with study follow-up

          9. Women with child-bearing potential must agree to practice an adequate (barrier) method
             of birth control or to abstain from heterosexual intercourse during study therapy.

         10. HIV negative, or HIV-positive with CD4 > 200 cells/cu mm

         11. Laboratory parameters done at, or 14 days prior to, screening (with results available
             for review by study personnel):

               -  Serum alanine aminotransferase (ALT) activity ≤ 2 times the upper limit of normal

               -  Serum total bilirubin level ≤ 2 times the upper limit of normal

               -  Serum creatinine level less than or equal to the upper limit of normal

               -  Hemoglobin level of at least 7.0 g/dL

               -  Platelet count of at least 100,000/mm3

               -  Negative pregnancy test (women of childbearing potential)

        Exclusion Criteria:

          1. Pregnant or breast-feeding

          2. Known intolerance or allergy to any of the study drugs

          3. Concomitant disorders or conditions for which isoniazid (INH), rifamycins,
             pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe
             hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty
             arthritis.

          4. Current or planned therapy, during the intensive phase of TB therapy with cyclosporine
             or tacrolimus, or HIV antiretroviral (ARV) therapy, which have unacceptable
             interactions with rifamycins.

          5. Any medical or psychosocial condition, which, in the view of the study investigator,
             makes study participation inadvisable.

          6. Pulmonary silicosis

          7. Central nervous system TB