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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01225640

Enrollment

Registered

2010-10-21

Start date

2011-08-31

Completion date

2011-12-31

Last updated

2016-01-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tuberculosis

Keywords

Tuberculosis, EBA, WBA

Brief summary

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.

Interventions

DRUGPNU-100480

600 mg twice daily (BID) for 14 days

DRUGRHZE

Combination tablet (RHZE) dosed by weight. Dosage strength per tablet is 150 mg Rifampicin (R)/75 mg Isoniazid (H)/400 mg Pyrazinamide (Z)/275 mg Ethambutol (E)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

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.

Design outcomes

Primary

Measure	Time frame
The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2.	Days 0-2

Secondary

Measure	Time frame
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.	Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up)
Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit	Day 1
Rate of change in sputum log CFU/mL count (extended EBA).	Days 2-14
Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP	Days 02-; 2-14; 0-14
Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK	Day 1

Countries

South Africa

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026