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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

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00759564
Collaborator
(none)
29
Enrollment
2
Locations
1
Arm
15.9
Duration (Months)
14.5
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Drug: CP-70,429 and PF-03709270
 Phase 1

Detailed Description

To evaluate the pharmacokinetics and safety.

Study Design

Study Type:
Interventional
Actual Enrollment :
29 participants
Allocation:
Non-Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
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 Start Date :
Nov 1, 2008
Actual Primary Completion Date :
Mar 1, 2010
Actual Study Completion Date :
Mar 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: IV CP-70,429 and cross over to PF-03709270

Drug: CP-70,429 and PF-03709270
Study Periods 1 and 2 will be separated by a minimum of 14 days. In Period 1, subjects will receive a single dose of CP-70429 (800 mg given as a 1.5 hour intravenous infusion), while in Period 2, subjects will receive a single oral dose of PF-03709270 (1000 mg).
Other Names:
  • CP-70,429 - sulopenem

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose [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)]

      PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429. Cmax of CP-70429 following CP-70,429 intravenous dose was reported.

    2. Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following CP-70,429 Intravenous Dose [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)]

    3. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following CP-70,429 Intravenous Dose [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)]

      Area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration (AUClast).

    4. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70,429 Following CP-70,429 Intravenous Dose [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)]

      AUC (0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

    5. Renal Clearance (CLr) of CP-70429 Following CP-70,429 Intravenous Dose [0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose]

      Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).

    6. Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following PF-03709270 Oral Dose [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)]

      PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429. Cmax of CP-70429 following CP-70,429 intravenous dose was reported.

    7. Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following PF-03709270 Oral Dose [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)]

    8. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following PF-03709270 Oral Dose [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)]

      Area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration (AUClast).

    9. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70429 Following PF-03709270 Oral Dose [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)]

      AUC (0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

    10. Renal Clearance (CLr) of CP-70429 Following PF-03709270 Oral Dose [0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose]

      Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).

    Secondary Outcome Measures

    1. Terminal Elimination Half Life (t1/2) of CP-70429 Following CP-70,429 Intravenous Dose [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)]

      Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.

    2. Terminal Elimination Half Life (t1/2) of CP-70429 Following PF-03709270 Oral Dose [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)]

      Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.

    3. Clearance (CL) [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)]

      Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing given intravenous dose by AUC inf. AUC inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

    4. Apparent Oral Clearance (CL/F) [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)]

      Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing the given oral dose by AUCinf. AUC inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

    5. Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following Intravenous Dose [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)]

      Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 microgram per milliliter (mcg/mL) at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

    6. Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following PF-03709270 Oral Dose [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)]

      Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

    7. Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following Intravenous Dose [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)]

      Duration was calculated by subtracting the time at which the plasma concentrations exceeded 1.0 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 1.0 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

    8. Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following PF-03709270 Oral Dose [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)]

      Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

    9. Pharmacokinetics of CP-70429 and PF-03709270 Metabolites [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)]

      PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429 and metabolites.

    10. Concentration Versus Time Summary of 2-Ethylbutyric Acid [1, 3, 8 hours post-dose]

      Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

    11. Concentration Versus Time Summary of Plasma Formate [1, 3, 8 hours post-dose]

      Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

    12. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to 7-10 days after the last dose of study drug (up to 32 days)]

      An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 7-10 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

    13. Number of Participants With Laboratory Abnormalities [Baseline up to 7-10 days after the last dose of study drug (up to 32 days)]

      Criteria for laboratory test abnormality: Hematology (hemoglobin, hematocrit, red blood corpuscles [RBC] count: less than [<]0.8*lower limit of normal [LLN], platelets: <0.5*LLN/greater than [>]1.75*upper limit of normal [ULN], leukocytes: <0.6*LLN or >1.5*ULN, lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN, basophils, eosinophil, monocytes: >1.2*ULN); Liver Function (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >0.3*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN); total bilirubin, direct bilirubin, indirect bilirubin: >1.5*ULN; Renal Function (blood urea nitrogen, creatinine: >1.3*ULN, uric acid: >1.2*ULN); Electrolytes (sodium: <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, bicarbonate: <0.9*LLN or >1.1*ULN; creatine kinase: >2.0*ULN; glucose fasting: <0.6*LLN or >1.5*ULN, urine white blood corpuscles [WBC] and RBC: greater than or equal to (>=) 6/High Power Field [HPF]).

    14. Number of Participants With Vital Sign Abnormalities [Baseline up to 7-10 days after the last dose of study drug (up to 32 days)]

      Criteria for vital signs abnormalities included supine/sitting pulse rate of <40 beats per minute (bpm) or >120 bpm, supine systolic blood pressure (SBP) of <90 millimeter of mercury (mmHg), >=30 mmHg maximum increase and decrease from baseline in same posture, supine diastolic blood pressure (DBP) of <50 mmHg, >=20 mmHg maximum increase and decrease from baseline in same posture, heart rate <=45 beats per minute (bpm) or >=120 bpm or decrease/increase of >=15 bpm.

    15. Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities [Baseline up to 7-10 days after the last dose of study drug (up to 32 days)]

      Criteria for abnormal ECG (12-lead) values were defined as: maximum PR interval >=300 millisecond (msec) and maximum increase of >=25 percent for baseline value of >200 msec and >=50% for baseline value of <=200 msec for PR interval, QRS interval >=200 msec; QT interval corrected using the Fridericia formula (QTcF) >=500 msec or increase of >45 msec.

    16. Number of Participants With Change From Baseline in Physical Examinations [Baseline, 7-10 days after the last dose of study drug]

      Physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any potential changes in physical status, as determined by the investigator. Any untoward findings identified on physical exams conducted after the administration of the first dose of study medication was captured as an adverse event.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Centurion Clinical Research Indianapolis Indiana United States 46260
    2 Pfizer Clinical Research Unit Bruxelles Belgium 1070

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00759564
    Other Study ID Numbers:
    • A8811009
    • 2009-017796-20
    First Posted:
    Sep 25, 2008
    Last Update Posted:
    Mar 11, 2016
    Last Verified:
    Feb 1, 2016
    Additional relevant MeSH terms:
    Pneumonia
    Renal Insufficiency
    Lactams

    Study Results

    Participant Flow

    Recruitment Details This was a fixed sequence design study (not a complete 2 way crossover) in parallel groups of participants with varying degrees of renal impairment, where all subjects received the intravenous formulation in first period and then received the oral formulation in second period.
    Pre-assignment Detail Participants were planned to receive CP-70,429 800 milligram (mg) in all reporting groups. For severe renal impairment group, CP-70,429 dose was decreased from 800 mg to 200 mg as per protocol amendment. Only 1 participant received 800 mg dose and was excluded from all descriptive and statistical analyses as per change in planned analysis.
    Arm/Group Title CP-70,429 (800 mg) + PF-03709270: Normal Renal Function CP-70,429 (800 mg) + PF-03709270: Mild Renal Impairment CP-70,429 (800 mg) + PF-03709270: Moderate Renal Impairment CP-70,429 (800 mg) + PF-03709270: Severe Renal Impairment CP-70,429 (200 mg) + PF-03709270: Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by creatinine clearance [CLcr] greater than [>] 80 milliliter per minute [mL/min]) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with mild renal impairment (defined by CLcr >50 and less than or equal to [<=] 80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with moderate renal impairment (defined by CLcr greater than or equal to >=30 and <=50 mL/min) received a single dose of CP--70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP--70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF--03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period.
    Period Title: First Intervention Period (4 Days)
    STARTED 8 8 8 1 4
    COMPLETED 8 8 8 1 4
    NOT COMPLETED 0 0 0 0 0
    Period Title: First Intervention Period (4 Days)
    STARTED 8 8 8 1 4
    COMPLETED 8 8 8 1 3
    NOT COMPLETED 0 0 0 0 1
    Period Title: First Intervention Period (4 Days)
    STARTED 8 8 8 1 3
    COMPLETED 8 8 8 1 3
    NOT COMPLETED 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title CP-70,429 (800 mg) + PF-03709270: Normal Renal Impairment CP-70,429 (800 mg) + PF-03709270: Mild Renal Impairment CP-70,429 (800 mg) + PF-03709270: Moderate Renal Impairment CP-70,429 (800 mg) + PF-03709270: Severe Renal Impairment CP-70,429 (200 mg) + PF-03709270: Severe Renal Function Total
    Arm/Group Description Participants with normal renal function (defined by creatinine clearance [CLcr] greater than [>] 80 milliliter per minute [mL/min]) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with mild renal impairment (defined by CLcr >50 and less than or equal to [<=] 80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with moderate renal impairment (defined by CLcr greater than or equal to >=30 and <=50 mL/min) received a single dose of CP--70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF-03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP--70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period followed by a single oral dose of PF--03709270 1000 mg in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Total of all reporting groups
    Overall Participants 8 8 8 1 4 29
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.4
    (3.2)
    60.6
    (7.3)
    64.3
    (15.7)
    55
    (NA)
    69
    (9.4)
    62.5
    (9.9)
    Sex: Female, Male (Count of Participants)
    Female
    3
    37.5%
    3
    37.5%
    2
    25%
    0
    0%
    4
    100%
    12
    41.4%
    Male
    5
    62.5%
    5
    62.5%
    6
    75%
    1
    100%
    0
    0%
    17
    58.6%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose
    Description PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429. Cmax of CP-70429 following CP-70,429 intravenous dose was reported.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]
    17700
    (1880.3)
    22070
    (3420.8)
    28940
    (6880.0)
    10340
    (2784.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Mild Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed Cmax for mild renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 124.71
    Confidence Interval (2-Sided) 90%
    106.57 to 145.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Moderate Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed Cmax for moderate renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 163.51
    Confidence Interval (2-Sided) 90%
    139.72 to 191.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (200 mg): Severe Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed Cmax for severe renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 58.40
    Confidence Interval (2-Sided) 90%
    48.16 to 70.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following CP-70,429 Intravenous Dose
    Description
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Median (Full Range) [hours]
    1.00
    (11)
    1.50
    (15)
    1.50
    (23)
    1.50
    (26)
    3. Primary Outcome
    Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following CP-70,429 Intravenous Dose
    Description Area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration (AUClast).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [nanogram*hour per milliliter (ng*hr/mL)]
    31990
    (4793.3)
    53610
    (10520)
    78940
    (23937)
    34270
    (8430.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Mild Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUClast for mild renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 167.59
    Confidence Interval (2-Sided) 90%
    137.27 to 204.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Moderate Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUClast for moderate renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 246.76
    Confidence Interval (2-Sided) 90%
    202.11 to 301.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (200 mg): Severe Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUClast for severe renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 107.13
    Confidence Interval (2-Sided) 90%
    88.06 to 130.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Primary Outcome
    Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70,429 Following CP-70,429 Intravenous Dose
    Description AUC (0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [ng*hr/mL]
    32160
    (4775.5)
    54070
    (10647)
    79870
    (24619)
    35410
    (9610.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Mild Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUCinf for mild renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 168.14
    Confidence Interval (2-Sided) 90%
    137.40 to 205.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Moderate Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUCinf for moderate renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 248.38
    Confidence Interval (2-Sided) 90%
    202.98 to 303.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (200 mg): Severe Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUCinf for severe renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 110.12
    Confidence Interval (2-Sided) 90%
    89.84 to 134.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Primary Outcome
    Title Renal Clearance (CLr) of CP-70429 Following CP-70,429 Intravenous Dose
    Description Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).
    Time Frame 0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [liter per hour (L/hr)]
    8.035
    (5.578)
    6.936
    (2.516)
    3.043
    (3.297)
    2.303
    (0.605)
    6. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following PF-03709270 Oral Dose
    Description PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429. Cmax of CP-70429 following CP-70,429 intravenous dose was reported.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF--03709270 (1000 mg): Normal Renal Function PF--03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF--03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [ng/mL]
    2747
    (420.58)
    3704
    (1053.3)
    6215
    (1841.3)
    7830
    (738.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Mild Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed Cmax for mild renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 134.86
    Confidence Interval (2-Sided) 90%
    109.88 to 165.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Moderate Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed Cmax for moderate renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 226.28
    Confidence Interval (2-Sided) 90%
    184.36 to 277.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (200 mg): Severe Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed Cmax for severe renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 285.05
    Confidence Interval (2-Sided) 90%
    221.80 to 366.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Primary Outcome
    Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following PF-03709270 Oral Dose
    Description
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF--03709270 (1000 mg): Normal Renal Function PF--03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF--03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Median (Full Range) [hours]
    1.50
    (11)
    2.50
    (15)
    1.50
    (23)
    2.50
    (26)
    8. Primary Outcome
    Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following PF-03709270 Oral Dose
    Description Area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration (AUClast).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF--03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [ng*hr/mL]
    6403
    (1355.9)
    13400
    (4948.8)
    22600
    (9034.3)
    47560
    (15782)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Mild Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUClast for mild renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 209.31
    Confidence Interval (2-Sided) 90%
    158.81 to 275.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Moderate Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUClast for moderate renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 353.00
    Confidence Interval (2-Sided) 90%
    267.83 to 465.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (200 mg): Severe Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUClast for severe renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 742.68
    Confidence Interval (2-Sided) 90%
    529.59 to 1041.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Primary Outcome
    Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70429 Following PF-03709270 Oral Dose
    Description AUC (0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF--03709270 (1000 mg): Normal Renal Function PF--03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [ng*hr/mL]
    6523
    (1329.5)
    13670
    (5088.1)
    23040
    (9403.9)
    47990
    (16191)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Mild Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUCinf for mild renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 209.55
    Confidence Interval (2-Sided) 90%
    158.72 to 276.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (800 mg): Moderate Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUCinf for moderate renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 353.26
    Confidence Interval (2-Sided) 90%
    267.57 to 466.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection CP-70,429 (800 mg): Normal Renal Function, CP-70,429 (200 mg): Severe Renal Impairment
    Comments A one-way ANOVA model with group as a fixed effect was used to compare the natural log transformed AUCinf for severe renal impairment group (Test) to normal renal function group (Reference). The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Geometric Mean Ratio
    Estimated Value 735.77
    Confidence Interval (2-Sided) 90%
    523.56 to 1034.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Primary Outcome
    Title Renal Clearance (CLr) of CP-70429 Following PF-03709270 Oral Dose
    Description Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).
    Time Frame 0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF--03709270: Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [L/hr]
    15.47
    (1.885)
    7.952
    (2.537)
    4.239
    (2.647)
    3.294
    (4.398)
    11. Secondary Outcome
    Title Terminal Elimination Half Life (t1/2) of CP-70429 Following CP-70,429 Intravenous Dose
    Description Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Mean (Standard Deviation) [hours]
    1.034
    (0.216)
    1.660
    (0.586)
    1.823
    (0.269)
    2.313
    (0.579)
    12. Secondary Outcome
    Title Terminal Elimination Half Life (t1/2) of CP-70429 Following PF-03709270 Oral Dose
    Description Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF--03709270: Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Mean (Standard Deviation) [hours]
    0.837
    (0.121)
    1.451
    (0.335)
    1.809
    (0.566)
    2.750
    (0.832)
    13. Secondary Outcome
    Title Clearance (CL)
    Description Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing given intravenous dose by AUC inf. AUC inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [L/hr]
    24.87
    (3.9001)
    14.79
    (2.6787)
    10.01
    (3.7432)
    5.648
    (1.2500)
    14. Secondary Outcome
    Title Apparent Oral Clearance (CL/F)
    Description Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing the given oral dose by AUCinf. AUC inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Geometric Mean (Standard Deviation) [L/hr]
    153.5
    (31.540)
    73.20
    (24.115)
    43.38
    (19.719)
    20.86
    (6.8699)
    15. Secondary Outcome
    Title Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following Intravenous Dose
    Description Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 microgram per milliliter (mcg/mL) at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Median (Full Range) [hours]
    5.310
    (0.641)
    8.855
    (1.542)
    11.40
    (3.389)
    10.70
    (4.009)
    16. Secondary Outcome
    Title Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following PF-03709270 Oral Dose
    Description Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF--03709270: Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Median (Full Range) [hours]
    3.915
    (0.121)
    6.440
    (0.335)
    8.185
    (0.566)
    18.30
    (0.832)
    17. Secondary Outcome
    Title Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following Intravenous Dose
    Description Duration was calculated by subtracting the time at which the plasma concentrations exceeded 1.0 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 1.0 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period.
    Measure Participants 8 8 8 4
    Median (Full Range) [hours]
    3.935
    (0.461)
    7.190
    (0.849)
    9.240
    (2.161)
    7.710
    (2.304)
    18. Secondary Outcome
    Title Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following PF-03709270 Oral Dose
    Description Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF--03709270 (1000 mg): Moderate Renal Impairment PF--03709270: Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF--03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    Median (Full Range) [hours]
    2.895
    (0.121)
    4.990
    (0.335)
    6.320
    (0.566)
    12.15
    (0.832)
    19. Secondary Outcome
    Title Pharmacokinetics of CP-70429 and PF-03709270 Metabolites
    Description PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429 and metabolites.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    Data was not collected for this outcome because the metabolite data for CP-70,429 and PF-03709270 were not analyzed as per change in planned analysis
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 0 0 0 0
    20. Secondary Outcome
    Title Concentration Versus Time Summary of 2-Ethylbutyric Acid
    Description Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.
    Time Frame 1, 3, 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    1 hour
    46.38
    (96.048)
    19.00
    (53.740)
    15.25
    (43.134)
    NA
    (NA)
    3 hours
    20.00
    (56.569)
    17.63
    (49.851)
    NA
    (NA)
    NA
    (NA)
    8 hours
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    21. Secondary Outcome
    Title Concentration Versus Time Summary of Plasma Formate
    Description Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.
    Time Frame 1, 3, 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 4
    1 hour
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    3 hours
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    8 hours
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    22. Secondary Outcome
    Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 7-10 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
    Time Frame Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received the study medication.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment received a single dose of CP-70,429 800 mg given as a 1.5-hour intravenous infusion under fasted condition in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 1 4 8 8 8 4
    AEs
    5
    (0.216) 62.5%
    5
    (0.586) 62.5%
    4
    (0.269) 50%
    0
    (0.579) 0%
    3
    (0.121) 75%
    6
    (0.335) 20.7%
    4
    (0.566) NaN
    6
    (0.831) NaN
    3
    NaN
    SAEs
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    23. Secondary Outcome
    Title Number of Participants With Laboratory Abnormalities
    Description Criteria for laboratory test abnormality: Hematology (hemoglobin, hematocrit, red blood corpuscles [RBC] count: less than [<]0.8*lower limit of normal [LLN], platelets: <0.5*LLN/greater than [>]1.75*upper limit of normal [ULN], leukocytes: <0.6*LLN or >1.5*ULN, lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN, basophils, eosinophil, monocytes: >1.2*ULN); Liver Function (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >0.3*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN); total bilirubin, direct bilirubin, indirect bilirubin: >1.5*ULN; Renal Function (blood urea nitrogen, creatinine: >1.3*ULN, uric acid: >1.2*ULN); Electrolytes (sodium: <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, bicarbonate: <0.9*LLN or >1.1*ULN; creatine kinase: >2.0*ULN; glucose fasting: <0.6*LLN or >1.5*ULN, urine white blood corpuscles [WBC] and RBC: greater than or equal to (>=) 6/High Power Field [HPF]).
    Time Frame Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received the study medication.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment received a single dose of CP-70,429 800 mg given as a 1.5-hour intravenous infusion under fasted condition in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 1 4 8 8 8 4
    Number [participants]
    2
    25%
    3
    37.5%
    7
    87.5%
    1
    100%
    4
    100%
    1
    3.4%
    3
    NaN
    8
    NaN
    4
    NaN
    24. Secondary Outcome
    Title Number of Participants With Vital Sign Abnormalities
    Description Criteria for vital signs abnormalities included supine/sitting pulse rate of <40 beats per minute (bpm) or >120 bpm, supine systolic blood pressure (SBP) of <90 millimeter of mercury (mmHg), >=30 mmHg maximum increase and decrease from baseline in same posture, supine diastolic blood pressure (DBP) of <50 mmHg, >=20 mmHg maximum increase and decrease from baseline in same posture, heart rate <=45 beats per minute (bpm) or >=120 bpm or decrease/increase of >=15 bpm.
    Time Frame Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received the study medication.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment received a single dose of CP-70,429 800 mg given as a 1.5-hour intravenous infusion under fasted condition in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 1 4 8 8 8 4
    Number [participants]
    0
    0%
    0
    0%
    1
    12.5%
    0
    0%
    1
    25%
    0
    0%
    1
    NaN
    2
    NaN
    0
    NaN
    25. Secondary Outcome
    Title Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
    Description Criteria for abnormal ECG (12-lead) values were defined as: maximum PR interval >=300 millisecond (msec) and maximum increase of >=25 percent for baseline value of >200 msec and >=50% for baseline value of <=200 msec for PR interval, QRS interval >=200 msec; QT interval corrected using the Fridericia formula (QTcF) >=500 msec or increase of >45 msec.
    Time Frame Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received the study medication.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment received a single dose of CP-70,429 800 mg given as a 1.5-hour intravenous infusion under fasted condition in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 1 4 8 8 8 4
    Number [participants]
    0
    0%
    3
    37.5%
    0
    0%
    0
    0%
    3
    75%
    1
    3.4%
    4
    NaN
    4
    NaN
    2
    NaN
    26. Secondary Outcome
    Title Number of Participants With Change From Baseline in Physical Examinations
    Description Physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any potential changes in physical status, as determined by the investigator. Any untoward findings identified on physical exams conducted after the administration of the first dose of study medication was captured as an adverse event.
    Time Frame Baseline, 7-10 days after the last dose of study drug

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received the study medication.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal Impairment
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment received a single dose of CP-70,429 800 mg given as a 1.5-hour intravenous infusion under fasted condition in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period.
    Measure Participants 8 8 8 1 4 8 8 8 4
    Number [participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN

    Adverse Events

    Time Frame Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
    Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
    Arm/Group Title CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal
    Arm/Group Description Participants with normal renal function (defined by CLcr >80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single dose of CP-70,429 800 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with severe renal impairment received a single dose of CP-70,429 800 mg given as a 1.5-hour intravenous infusion under fasted condition in first intervention period. Participants with severe renal impairment (defined by CLcr <30 mL/min) received a single dose of CP-70,429 200 mg given as an intravenous infusion over 1.5 hours in first intervention period. Participants with normal renal function (defined by CLcr >80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with mild renal impairment (defined by CLcr >50 and <=80 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with moderate renal impairment (defined by CLcr >=30 and <=50 mL/min) received a single oral dose of PF-03709270 1000 mg tablet in second intervention period. Participants with severe renal impairment received a single oral dose of PF-03709270 1000 mg tablet under fasted condition in second intervention period.
    All Cause Mortality
    CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 1/4 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Injury, poisoning and procedural complications
    Fall 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 1/4 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Humerus fracture 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 1/4 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Other (Not Including Serious) Adverse Events
    CP-70,429 (800 mg): Normal Renal Function CP-70,429 (800 mg): Mild Renal Impairment CP-70,429 (800 mg): Moderate Renal Impairment CP-70,429 (800 mg): Severe Renal Impairment CP-70,429 (200 mg): Severe Renal Impairment PF-03709270 (1000 mg): Normal Renal Function PF-03709270 (1000 mg): Mild Renal Impairment PF-03709270 (1000 mg): Moderate Renal Impairment PF-03709270 (1000 mg): Severe Renal
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/8 (62.5%) 5/8 (62.5%) 4/8 (50%) 0/1 (0%) 3/4 (75%) 6/8 (75%) 4/8 (50%) 6/8 (75%) 3/4 (75%)
    Eye disorders
    Lacrimation increased 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Vision blurred 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/4 (0%)
    Abdominal tenderness 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Diarrhoea 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/1 (0%) 0/4 (0%) 4/8 (50%) 1/8 (12.5%) 2/8 (25%) 1/4 (25%)
    Dyspepsia 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/4 (0%)
    Faeces discoloured 2/8 (25%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 2/8 (25%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Flatulence 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/4 (0%)
    Mucous stools 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/4 (0%)
    Nausea 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/4 (0%)
    General disorders
    Chest discomfort 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Chills 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/4 (0%)
    Feeling jittery 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/4 (0%)
    Infusion site pain 0/8 (0%) 0/8 (0%) 2/8 (25%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 1/4 (25%)
    Infections and infestations
    Nasopharyngitis 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/4 (0%)
    Subcutaneous abscess 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Upper respiratory tract infection 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 1/4 (25%)
    Injury, poisoning and procedural complications
    Contusion 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 1/4 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Fall 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Rib fracture 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Investigations
    Blood bilirubin increased 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Blood glucose decreased 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 1/4 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Urine analysis abnormal 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Metabolism and nutrition disorders
    Hypoglycaemia 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Back pain 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Pain in extremity 0/8 (0%) 0/8 (0%) 2/8 (25%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Nervous system disorders
    Headache 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 1/4 (25%) 0/8 (0%) 1/8 (12.5%) 3/8 (37.5%) 1/4 (25%)
    Syncope 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Dizziness 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Renal and urinary disorders
    Urine odour abnormal 4/8 (50%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 3/8 (37.5%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 1/4 (25%)
    Oropharyngeal pain 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 1/4 (25%)
    Respiratory tract congestion 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 1/4 (25%)
    Skin and subcutaneous tissue disorders
    Cold sweat 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 1/8 (12.5%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Hyperhidrosis 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 1/8 (12.5%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Pruritus 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 1/4 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Swelling face 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/4 (0%)
    Vascular disorders
    Angiopathy 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)
    Flushing 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 0/1 (0%) 0/4 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/4 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00759564
    Other Study ID Numbers:
    • A8811009
    • 2009-017796-20
    First Posted:
    Sep 25, 2008
    Last Update Posted:
    Mar 11, 2016
    Last Verified:
    Feb 1, 2016