Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

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

10. Februar 2016 aktualisiert von: Pfizer

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

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).

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

To evaluate the pharmacokinetics and safety.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

29

Phase

  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Belgien
      • Bruxelles, Belgien, 1070
        • Pfizer Clinical Research Unit
  • Vereinigte Staaten
    • Indiana
      • Indianapolis, Indiana, Vereinigte Staaten, 46260
        • Centurion Clinical Research

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 85 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Ja

Studienberechtigte Geschlechter

Alle

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Crossover-Aufgabe
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: IV CP-70,429 and cross over to PF-03709270
Arzneimittel: 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).
Andere Namen:
  • CP-70,429 - sulopenem

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose
Zeitfenster: 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.
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)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following CP-70,429 Intravenous Dose
Zeitfenster: 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)
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 Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following CP-70,429 Intravenous Dose
Zeitfenster: 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).
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 Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70,429 Following CP-70,429 Intravenous Dose
Zeitfenster: 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).
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)
Renal Clearance (CLr) of CP-70429 Following CP-70,429 Intravenous Dose
Zeitfenster: 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).
0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following PF-03709270 Oral Dose
Zeitfenster: 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.
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)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following PF-03709270 Oral Dose
Zeitfenster: 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)
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 Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following PF-03709270 Oral Dose
Zeitfenster: 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).
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 Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70429 Following PF-03709270 Oral Dose
Zeitfenster: 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).
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)
Renal Clearance (CLr) of CP-70429 Following PF-03709270 Oral Dose
Zeitfenster: 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).
0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Terminal Elimination Half Life (t1/2) of CP-70429 Following CP-70,429 Intravenous Dose
Zeitfenster: 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.
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 (t1/2) of CP-70429 Following PF-03709270 Oral Dose
Zeitfenster: 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.
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 (CL)
Zeitfenster: 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).
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)
Apparent Oral Clearance (CL/F)
Zeitfenster: 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).
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 of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following Intravenous Dose
Zeitfenster: 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.
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 of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following PF-03709270 Oral Dose
Zeitfenster: 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.
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 of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following Intravenous Dose
Zeitfenster: 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.
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 of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following PF-03709270 Oral Dose
Zeitfenster: 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.
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)
Pharmacokinetics of CP-70429 and PF-03709270 Metabolites
Zeitfenster: 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.
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)
Concentration Versus Time Summary of 2-Ethylbutyric Acid
Zeitfenster: 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.
1, 3, 8 hours post-dose
Concentration Versus Time Summary of Plasma Formate
Zeitfenster: 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.
1, 3, 8 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Zeitfenster: 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.
Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
Number of Participants With Laboratory Abnormalities
Zeitfenster: 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]).
Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
Number of Participants With Vital Sign Abnormalities
Zeitfenster: 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.
Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
Zeitfenster: 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.
Baseline up to 7-10 days after the last dose of study drug (up to 32 days)
Number of Participants With Change From Baseline in Physical Examinations
Zeitfenster: 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.
Baseline, 7-10 days after the last dose of study drug

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Pfizer

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. November 2008

Primärer Abschluss (Tatsächlich)

1. März 2010

Studienabschluss (Tatsächlich)

1. März 2010

Studienanmeldedaten

Zuerst eingereicht

23. September 2008

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

24. September 2008

Zuerst gepostet (Schätzen)

25. September 2008

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

11. März 2016

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

10. Februar 2016

Zuletzt verifiziert

1. Februar 2016

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • A8811009
  • 2009-017796-20 (EudraCT-Nummer)

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Abonnieren