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

December 14, 2015 updated by: Sequella, Inc.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
      • Cape Town, South Africa, 7700
        • Pfizer Investigational Site
    • Cape Town
      • Bellville, Cape Town, South Africa, 7530
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PNU-100480 600 mg BID
Drug: PNU-100480
600 mg twice daily (BID) for 14 days
Drug: PNU-100480
1200 mg once daily (QD) for 14 days
Experimental: PNU-100480 1200 mg QD
Drug: PNU-100480
600 mg twice daily (BID) for 14 days
Drug: PNU-100480
1200 mg once daily (QD) for 14 days
Active Comparator: RHZE
conjugated tablet with 4 drug combination of RHZE, Rifafour® e275 will be used in countries where can be sourced locally
Drug: RHZE
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)
Other Names:
  • Rifafour, Rimstar

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Rate of change in sputum log CFU/mL count (extended EBA).
Time Frame: Days 2-14
Days 2-14
Rate of change in sputum log CFU/mL count (extended EBA).
Time Frame: Days 0-14
Days 0-14
Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP
Time Frame: Days 02-; 2-14; 0-14
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
Time Frame: Day 1
Day 1
Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK
Time Frame: Day 13-14
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
Time Frame: Day 1
Day 1
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
Time Frame: Day 13-14
Day 13-14
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Time Frame: Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up)
Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up)
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Time Frame: ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up
ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Time Frame: Lab tests at Screening, Day 1, Day 15 and 42/Follow-up
Lab tests at Screening, Day 1, Day 15 and 42/Follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sequella, Inc.

Investigators

  • Study Director: Lisa Beth Ferstenberg, M.D., Sequella, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

October 19, 2010

First Submitted That Met QC Criteria

October 19, 2010

First Posted (Estimate)

October 21, 2010

Study Record Updates

Last Update Posted (Estimate)

January 14, 2016

Last Update Submitted That Met QC Criteria

December 14, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B1171003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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