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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00990990
First Posted: October 7, 2009
Last Update Posted: August 28, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Sequella, Inc.
  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
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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:


Further study details as provided by Sequella, Inc.:

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 ]

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 ]
  • 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 ]
  • 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 ]
  • 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 ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00990990


Locations
United States, Connecticut
Pfizer Investigational Site
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Sequella, Inc.
Investigators
Study Director: Lisa Beth Ferstenberg, M.D. Sequella, Inc.
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sequella, Inc.
ClinicalTrials.gov Identifier: NCT00990990     History of Changes
Other Study ID Numbers: B1171002
First Submitted: October 6, 2009
First Posted: October 7, 2009
Last Update Posted: August 28, 2013
Last Verified: August 2013

Keywords provided by Sequella, Inc.:
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
Linezolid
Pyrazinamide
Oxazolidinones
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antitubercular Agents