Clinical trial NCT00990990: Safety, Tolerability, Pharmacokinetics And Measurement Of Whole Blood Activity (WBA) Of PNU-100480 After Multiple Oral Doses In Healthy Adult Volunteers
Official title: A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PNU-100480 (PF-02341272) After Administration Of Multiple Escalating Oral Doses To Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: Safety tolerability pharmacokinetics (PK) pharmacodynamics whole blood activity (WBA) PNU-100480 linezolid pyrazinamide multiple dose
Lead sponsor: Sequella, Inc.
Sponsor class: INDUSTRY
First posted: 2009-10-07
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The purpose of this study is to assess the safety, tolerability and pharmacokinetics of multiple doses of PNU-100480 given for 14 or 28 days. Killing activity against the bacterium that causes tuberculosis (TB) will also be measured. The effect of adding an additional tuberculosis (TB) agent (given for 2 days) in addition to PNU-100480 will be evaluated. Linezolid open label to determine activity in whole blood assay (WBA).

Detailed description: Evaluate safety, tolerability, pharmacokinetics and whole blood activity (WBA) of PNU-100480 given for 14 or 28 days; evaluate WBA of PNU with pyrazinamide; evaluate WBA of linezolid

Eligibility criteria: Inclusion Criteria:

* Healthy adult volunteers willing and able to be confined to the Clinical Research Unit and comply with study schedule.
* Women of non-childbearing potential only.

Exclusion Criteria:

* History of hypersensitivity to, or intolerance of, linezolid.
* Antibiotic treatment within 14 days prior to dosing, or any previous antibiotic use at the discretion of the investigator.
* Previous history of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).

Primary outcomes:
measure: To evaluate the safety and tolerability of ascending oral doses of PNU-100480 administered as extemporaneously prepared suspension (EPS) over 14 and 28 days in healthy adult volunteers.
timeFrame: Monitor adverse events daily; safety eval pre-dose, specified times , discharge, follow-up/as needed
Secondary outcomes:
measure: To characterize the single dose and steady state pharmacokinetics of ascending oral doses of PNU-100480 administered over 14 and 28 days in healthy adult volunteers with regard to the parent drug and its metabolites.
timeFrame: Full and sparse PK sampling from Day 1 through final day of dosing
measure: To characterize the bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis in relation to blood concentrations ofPNU-100480 and its metabolites.
timeFrame: Full and sparse sampling from Day 1 through final day of dosing
measure: To characterize the effect of once a day administration of pyrazinamide for 2 days on the pharmacokinetics and bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis (Cohorts 5 and 6, Days 27-28 only).
timeFrame: Days 27-28 as applicable
measure: To characterize pharmacokinetics and bactericidal activity in blood of orally administered linezolid against intracellular M. tuberculosis following 4 days of QD dosing.
timeFrame: As applicable up to Day 4
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer Investigational Site
state: Connecticut
Study officials:
affiliation: Sequella, Inc.
name: Lisa Beth Ferstenberg, M.D.
role: STUDY_DIRECTOR
References:
citation: Wallis RS, Jakubiec WM, Kumar V, Silvia AM, Paige D, Dimitrova D, Li X, Ladutko L, Campbell S, Friedland G, Mitton-Fry M, Miller PF. Pharmacokinetics and whole-blood bactericidal activity against Mycobacterium tuberculosis of single doses of PNU-100480 in healthy volunteers. J Infect Dis. 2010 Sep 1;202(5):745-51. doi: 10.1086/655471.