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

Phase 2

Completed

• Conditions: Tuberculosis
• Interventions: Drug: PNU-100480; Drug: RHZE

• Registration Number: NCT01225640
• Lead Sponsor: Sequella, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-10-19
• Study First Submitted QC: 2010-10-19
• Study First Posted: 2010-10-21
• Study Start: 2011-08
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Disposition First Submitted: 2013-03-19
• Disposition First Submitted QC: 2013-03-19
• Disposition First Posted: 2013-03-25
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-14
• Last Update Posted: 2016-01-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PNU-100480 1200 mg QD	PNU-100480	-
PNU-100480 600 mg BID	PNU-100480	-
RHZE	RHZE	conjugated tablet with 4 drug combination of RHZE, Rifafour® e275 will be used in countries where can be sourced locally

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 13-14
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 13-14
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.	Lab tests at Screening, Day 1, Day 15 and 42/Follow-up
Rate of change in sputum log CFU/mL count (extended EBA).	Days 0-14

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇿🇦 Cape Town, South Africa