Clinical trial NCT01225640: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis
EBA
WBA
Lead sponsor: Sequella, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-21
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2.
timeFrame: Days 0-2
Secondary outcomes:
measure: Rate of change in sputum log CFU/mL count (extended EBA).
timeFrame: Days 2-14
measure: Rate of change in sputum log CFU/mL count (extended EBA).
timeFrame: Days 0-14
measure: Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP
timeFrame: Days 02-; 2-14; 0-14
measure: Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK
timeFrame: Day 1
measure: Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK
timeFrame: Day 13-14
measure: 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
timeFrame: Day 1
measure: 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
timeFrame: Day 13-14
measure: Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
timeFrame: Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up)
measure: Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
timeFrame: ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up
measure: Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
timeFrame: Lab tests at Screening, Day 1, Day 15 and 42/Follow-up
Other outcomes:
Locations:
city: Bellville
country: South Africa
facility: Pfizer Investigational Site
state: Cape Town
city: Cape Town
country: South Africa
facility: Pfizer Investigational Site
Study officials:
affiliation: Sequella, Inc.
name: Lisa Beth Ferstenberg, M.D.
role: STUDY_DIRECTOR
References:
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.