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:
Information provided by (Responsible Party):
Sequella, Inc.
ClinicalTrials.gov Identifier:
NCT00990990
First received: October 6, 2009
Last updated: August 27, 2013
Last verified: August 2013
  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:


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 ] [ 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
Sequella, Inc.
Investigators
Study Director: Lisa Beth Ferstenberg, M.D. Sequella, Inc.
  More Information

Additional Information:
No publications provided by Sequella, Inc.

Additional 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
Study First Received: October 6, 2009
Last Updated: August 27, 2013
Health Authority: United States: Food and Drug Administration

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
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 April 22, 2014