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

Sequella

Status and phase: Completed; Phase 2

Conditions: Tuberculosis

Treatments: Drug: RHZE; Drug: PNU-100480

Study type: Interventional

Funder types: Industry

Identifiers

NCT01225640

B1171003

Details and patient eligibility

About

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.

Enrollment: 59 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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59 participants in 3 patient groups

PNU-100480 600 mg BID

Experimental group

Treatment:

Drug: PNU-100480

Drug: PNU-100480

PNU-100480 1200 mg QD

Experimental group

Treatment:

Drug: PNU-100480

Drug: PNU-100480

RHZE

Active Comparator group

Description:

conjugated tablet with 4 drug combination of RHZE, Rifafour® e275 will be used in countries where can be sourced locally

Treatment:

Drug: RHZE