Safety, Tolerability, Pharmacokinetics And Measurement Of Whole Blood Activity (WBA) Of PNU-100480 After Multiple Oral Doses In Healthy Adult Volunteers

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00990990

Enrollment

Registered

2009-10-07

Start date

2009-10-31

Completion date

2010-05-31

Last updated

2013-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tuberculosis

Keywords

Safety tolerability pharmacokinetics (PK) pharmacodynamics whole blood activity (WBA) PNU-100480 linezolid pyrazinamide multiple dose

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

Interventions

DRUGPNU-100480

100 mg BID for 14 days

DRUGPlacebo

to match 100 mg BID for 14 days

DRUGLinezolid

300 mg QD for 4 days (open label)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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).

Design outcomes

Primary

Measure	Time frame
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.	Monitor adverse events daily; safety eval pre-dose, specified times , discharge, follow-up/as needed

Secondary

Measure	Time frame
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.	Full and sparse PK sampling from Day 1 through final day of dosing
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.	Full and sparse sampling from Day 1 through final day of dosing
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).	Days 27-28 as applicable
To characterize pharmacokinetics and bactericidal activity in blood of orally administered linezolid against intracellular M. tuberculosis following 4 days of QD dosing.	As applicable up to Day 4

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026