Clinical trial NCT00759564: A Study To Investigate The Pharmacokinetics, Safety And Tolerability Of An Intravenous And Oral Form Of A Compound In Subjects With Varying Degrees Of Renal Impairment And Normal Renal Function
Official title: An Open-label, 2-way Crossover Study To Investigate The Pharmacokinetics, Safety And Tolerability Of Iv Cp-70429 And Oral Pf-03709270 In Subjects With Varying Degrees Of Renal Impairment And Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pneumonia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-09-25
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER

Brief summary: This study will evaluate what effect renal dysfunction has on a drug that has an intravenous (CP-70,429) and an oral form (PF-03709270).

Detailed description: To evaluate the pharmacokinetics and safety.

Eligibility criteria: Inclusion Criteria:

Subjects must meet one of the following renal function categories:

* Normal renal function (CLcr \>80 mL/min).
* Mild renal impairment (CLcr \>50 and \<80 mL/min).
* Moderate renal impairment (CLcr \>30 and \<50 mL/min).
* Severe renal impairment (CLcr \<30 mL/min).

Exclusion Criteria:

Women who are pregnant or nursing or women who are of childbearing potential. History of clinically significant allergies, including seasonal allergies, and especially drug hypersensitivity including known allergies to components of the study drug formulation, penicillin, carbapenems and/or cephalosporin antibiotics (eg, amoxicillin, amoxicillin/clavulanate, ampicillin, cefadroxil, cephalexin, cefaclor and cefixime).

Subjects should not have evidence of a history of the following:

* normal renal function: clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological or allergic disease.
* renal impairment: any clinically significant (hepatic, cardiac or pulmonary or subjects with acute nephritic syndrome) diseases (except diabetes). Stable co-morbid disease where it is unlikely that the disease and medication will alter the outcome of the study will be allowed.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following CP-70,429 Intravenous Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following CP-70,429 Intravenous Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70,429 Following CP-70,429 Intravenous Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Renal Clearance (CLr) of CP-70429 Following CP-70,429 Intravenous Dose
timeFrame: 0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70429 Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Renal Clearance (CLr) of CP-70429 Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose
Secondary outcomes:
measure: Terminal Elimination Half Life (t1/2) of CP-70429 Following CP-70,429 Intravenous Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Terminal Elimination Half Life (t1/2) of CP-70429 Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Clearance (CL)
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Apparent Oral Clearance (CL/F)
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following Intravenous Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following Intravenous Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following PF-03709270 Oral Dose
timeFrame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Pharmacokinetics of CP-70429 and PF-03709270 Metabolites
timeFrame: 0.5, 2, 4, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)
measure: Concentration Versus Time Summary of 2-Ethylbutyric Acid
timeFrame: 1, 3, 8 hours post-dose
measure: Concentration Versus Time Summary of Plasma Formate
timeFrame: 1, 3, 8 hours post-dose
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
measure: Number of Participants With Vital Sign Abnormalities
timeFrame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
measure: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
measure: Number of Participants With Change From Baseline in Physical Examinations
timeFrame: Baseline, 7-10 days after the last dose of study drug
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Centurion Clinical Research
state: Indiana
city: Bruxelles
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: