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

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 2

Locations

South Africa

Study Type

Interventional

Intervention

PNU-100480

RHZE

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring Tuberculosis, EBA, WBA

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Pfizer Investigational Site
Pfizer Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

PNU-100480 600 mg BID

PNU-100480 1200 mg QD

RHZE

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Rate of change in sputum log CFU/mL count (extended EBA).

Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP

Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK

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

Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.

Full Information

NCT ID

NCT01225640

First Posted

October 19, 2010

Last Updated

December 14, 2015

Sponsor

Sequella, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01225640

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sequella, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Tuberculosis, EBA, WBA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

59 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PNU-100480 600 mg BID

Arm Type

Experimental

Arm Title

PNU-100480 1200 mg QD

Arm Type

Experimental

Arm Title

RHZE

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

PNU-100480

Intervention Description

600 mg twice daily (BID) for 14 days

Intervention Type

Drug

Intervention Name(s)

PNU-100480

Intervention Description

1200 mg once daily (QD) for 14 days

Intervention Type

Drug

Intervention Name(s)

RHZE

Other Intervention Name(s)

Rifafour, Rimstar

Intervention Description

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)

Primary Outcome Measure Information:

Title

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

Time Frame

Days 0-2

Secondary Outcome Measure Information:

Title

Rate of change in sputum log CFU/mL count (extended EBA).

Time Frame

Days 2-14

Title

Rate of change in sputum log CFU/mL count (extended EBA).

Time Frame

Days 0-14

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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)

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lisa Beth Ferstenberg, M.D.

Organizational Affiliation

Sequella, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Pfizer Investigational Site

City

Bellville

State/Province

Cape Town

ZIP/Postal Code

7530

Country

South Africa

Facility Name

Pfizer Investigational Site

City

Cape Town

ZIP/Postal Code

7700

Country

South Africa

12. IPD Sharing Statement

Citations:

PubMed Identifier

24732289

Citation

Wallis RS, Dawson R, Friedrich SO, Venter A, Paige D, Zhu T, Silvia A, Gobey J, Ellery C, Zhang Y, Eisenach K, Miller P, Diacon AH. Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLoS One. 2014 Apr 14;9(4):e94462. doi: 10.1371/journal.pone.0094462. eCollection 2014.

Results Reference

derived

Learn more about this trial

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

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