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

Purpose

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).

Condition	Intervention	Phase
Tuberculosis	Drug: PNU-100480 Drug: Placebo Drug: Linezolid	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator)
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

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Pyrazinamide Linezolid

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

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. [ Time Frame: Monitor adverse events daily; safety eval pre-dose, specified times , discharge, follow-up/as needed ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. [ Time Frame: Full and sparse PK sampling from Day 1 through final day of dosing ] [ Designated as safety issue: No ]
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. [ Time Frame: Full and sparse sampling from Day 1 through final day of dosing ] [ Designated as safety issue: No ]
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). [ Time Frame: Days 27-28 as applicable ] [ Designated as safety issue: No ]
To characterize pharmacokinetics and bactericidal activity in blood of orally administered linezolid against intracellular M. tuberculosis following 4 days of QD dosing. [ Time Frame: As applicable up to Day 4 ] [ Designated as safety issue: No ]

Enrollment:	59
Study Start Date:	October 2009
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1	Drug: PNU-100480 100 mg BID for 14 days Drug: Placebo to match 100 mg BID for 14 days
Experimental: Cohort 2	Drug: PNU-100480 300 mg BID for 14 days Drug: Placebo to match 300 mg BID for 14 days
Experimental: Cohort 3	Drug: PNU-100480 600 mg BID for 14 days Drug: Placebo to match 600 mg BID for 14 days
Experimental: Cohort 4	Drug: PNU-100480 1200 mg QD for 14 days Drug: Placebo to match 1200 mg QD for 14 days
Experimental: Cohort 5	Drug: PNU-100480 600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28 Drug: Placebo placebo to match 600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
Experimental: Cohort 6 (optional)	Drug: PNU-100480 PNU-100480 dose up to total of 1200 mg daily for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28 Drug: Placebo placebo to match dose up to total of 1200 mg daily for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
Experimental: Linezolid Cohort	Drug: Linezolid 300 mg QD for 4 days (open label)

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

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990990

Locations

United States, Connecticut
Pfizer Investigational Site
New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00990990 History of Changes
Other Study ID Numbers:	B1171002
Study First Received:	October 6, 2009
Last Updated:	June 29, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

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

Additional relevant MeSH terms:

Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Pyrazinamide
Linezolid
Oxazolidinones

Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013