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
2016년 2월 10일 업데이트: 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).
연구 개요
상세 설명
To evaluate the pharmacokinetics and safety.
연구 유형
중재적
등록 (실제)
29
단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
예
연구 대상 성별
모두
설명
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.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 할당: 무작위화되지 않음
- 중재 모델: 크로스오버 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: IV CP-70,429 and cross over to 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).
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Terminal Elimination Half Life (t1/2) of CP-70429 Following CP-70,429 Intravenous Dose
기간: 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
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
스폰서
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2008년 11월 1일
기본 완료 (실제)
2010년 3월 1일
연구 완료 (실제)
2010년 3월 1일
연구 등록 날짜
최초 제출
2008년 9월 23일
QC 기준을 충족하는 최초 제출
2008년 9월 24일
처음 게시됨 (추정)
2008년 9월 25일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2016년 3월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2016년 2월 10일
마지막으로 확인됨
2016년 2월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .