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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00990990
• Other study ID #: B1171002
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2009
• Last updated: August 27, 2013
• Start date: October 2009
• Est. completion date: May 2010

Study information

• Verified date: August 2013
• Source: Sequella, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• PNU-100480
100 mg BID for 14 days
• Placebo
to match 100 mg BID for 14 days
• PNU-100480
300 mg BID for 14 days
• Placebo
to match 300 mg BID for 14 days
• PNU-100480
600 mg BID for 14 days
• Placebo
to match 600 mg BID for 14 days
• PNU-100480
1200 mg QD for 14 days
• Placebo
to match 1200 mg QD for 14 days
• PNU-100480
600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
• Placebo
placebo to match 600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
• 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
• 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
• Linezolid
300 mg QD for 4 days (open label)

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Sequella, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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