NCT00990990

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
59

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Oct 2009

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2009

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

October 6, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 7, 2009

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2010

Completed
Last Updated

August 28, 2013

Status Verified

August 1, 2013

Enrollment Period

7 months

First QC Date

October 6, 2009

Last Update Submit

August 27, 2013

Conditions

Tuberculosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • 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

Study Arms (7)

Cohort 1

EXPERIMENTAL
Drug: PNU-100480Drug: Placebo

Cohort 2

EXPERIMENTAL
Drug: PNU-100480Drug: Placebo

Cohort 3

EXPERIMENTAL
Drug: PNU-100480Drug: Placebo

Cohort 4

EXPERIMENTAL
Drug: PNU-100480Drug: Placebo

Cohort 5

EXPERIMENTAL
Drug: PNU-100480Drug: Placebo

Cohort 6 (optional)

EXPERIMENTAL
Drug: PNU-100480Drug: Placebo

Linezolid Cohort

EXPERIMENTAL
Drug: Linezolid

Interventions

PNU-100480DRUG

100 mg BID for 14 days

Cohort 1
PlaceboDRUG

to match 100 mg BID for 14 days

Cohort 1
LinezolidDRUG

300 mg QD for 4 days (open label)

Linezolid Cohort

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Pfizer Investigational Site

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

  • 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.

    PMID: 20629533DERIVED

Related Links

MeSH Terms

Conditions

Tuberculosis

Interventions

PNU-100480Linezolid

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

AcetamidesAmidesOrganic ChemicalsAcetatesAcids, AcyclicCarboxylic AcidsOxazolidinonesOxazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Lisa Beth Ferstenberg, M.D.

    Sequella, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 6, 2009

First Posted

October 7, 2009

Study Start

October 1, 2009

Primary Completion

May 1, 2010

Study Completion

May 1, 2010

Last Updated

August 28, 2013

Record last verified: 2013-08

Locations

US(1)