PNU-100480 In Newly Diagnosed, Drug Sensitive Patients With Pulmonary TB; Early Bactericidal Activity; Whole Blood Assay

A Phase 2a, Open-Label, Randomized Study In Treatment-Naive, Sputum Smear Positive Subjects With Drug-Sensitive Pulmonary Tuberculosis To Assess Early Bactericidal Activity (EBA) And Whole Blood Activity (WBA) Of PNU-100480 (PF-02341272)

PNU-100480 is being developed for the treatment of both drug resistant and sensitive tuberculosis. This is an efficacy and safety study to characterize the effect of PNU-100480 when given for 14 days to treatment-naive patients with drug-sensitive pulmonary tuberculosis.

Inclusion Criteria:

• Adult males or females between 18 and 65 years; women of childbearing potential must be willing to adhere to lifestyle requirements regarding contraception/pregnancy prevention.
• Newly diagnosed sputum smear-positive pulmonary TB confirmed with acid-fast bacillus (AFB) smear and chest x-ray. Patients with TB more than 5 years ago who completed treatment, are healthy, and meet other inclusion criteria may be included.
• Body weight between 40 and 90 kg, inclusive (in light clothing, no shoes).
• Reasonably normal hemoglobin (>=8 gm/dL), renal function (serum creatinine <2 mg/dL), hepatic function (serum AST <3xULN and total bilirubin <1.3 mg/dL), and random glucose <150 mg/dL.

Exclusion Criteria:

• HIV infection with helper/inducer T-lymphocytes (CD4 cell) count of <=350x10-6/L.
• Presence of significant hemoptysis. Subjects who cough up frank blood (more than blood streaked sputum) will not be eligible.
• Pregnant or nursing females; females of childbearing potential unwilling or unable to adhere to contraception guidelines.
• Significant respiratory impairment (respiratory rate >35/minute).
• Clinical suspicion of disseminated TB or tuberculosis meningitis.
• Subjects with diabetes mellitus on insulin and/or who have poorly controlled disease.
• Subjects with confirmed or suspected multi-drug resistant TB.