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

Tuberculosis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01225640
• Other study ID #: B1171003
• Status: Completed
• Phase: Phase 2
• First received: October 19, 2010
• Last updated: December 14, 2015
• Start date: August 2011
• Est. completion date: December 2011

Study information

• Verified date: December 2015
• Source: Sequella, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• PNU-100480
600 mg twice daily (BID) for 14 days
• PNU-100480
1200 mg once daily (QD) for 14 days
• 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)

Locations

Country	Name	City	State
South Africa	Pfizer Investigational Site	Bellville	Cape Town
South Africa	Pfizer Investigational Site	Cape Town

Sponsors (1)

Lead Sponsor	Collaborator
Sequella, Inc.

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2.		Days 0-2	No
Secondary	Rate of change in sputum log CFU/mL count (extended EBA).		Days 2-14	No
Secondary	Rate of change in sputum log CFU/mL count (extended EBA).		Days 0-14	No
Secondary	Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP		Days 02-; 2-14; 0-14	No
Secondary	Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK		Day 1	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	Yes
Secondary	Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.		ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up	Yes
Secondary	Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.		Lab tests at Screening, Day 1, Day 15 and 42/Follow-up	Yes