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

Phase 1

Completed

• Conditions: Tuberculosis
• Interventions: Drug: PNU-100480; Drug: Linezolid; Drug: Placebo

• Registration Number: NCT00990990
• Lead Sponsor: Sequella, Inc.

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

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2009-10-06
• Study First Submitted QC: 2009-10-06
• Study First Posted: 2009-10-07
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-27
• Last Update Posted: 2013-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 4	PNU-100480	-
Cohort 1	PNU-100480	-
Cohort 1	Placebo	-
Cohort 2	PNU-100480	-
Cohort 2	Placebo	-
Cohort 3	Placebo	-
Cohort 4	Placebo	-
Cohort 5	PNU-100480	-
Cohort 5	Placebo	-
Cohort 6 (optional)	PNU-100480	-
Cohort 6 (optional)	Placebo	-
Linezolid Cohort	Linezolid	-
Cohort 3	PNU-100480	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇺🇸 New Haven, Connecticut, United States