A Pharmacokinetic And QT Study Of CP-751,871 In Healthy Subjects

Phase 1

Terminated

Conditions: Healthy Volunteers

Interventions: Biological: CP-751,871
Biological: CP-751,871, moxifloxacin, saline

Registration Number: NCT00926263

Lead Sponsor: Pfizer

Brief Summary: This study is primarily to evaluate the single dose pharmacokinetics of CP-751,871 and its effect on QT interval prolongation.

Detailed Description: This study was terminated on October 30th, 2009. While the study was terminated due to adverse events and altered benefit/risk ratio in healthy subjects, the findings in healthy volunteers are not considered to alter the benefit/risk evaluation of figitumumab in cancer patients. No changes due to the termination of this study are anticipated in the conduct of the ongoing cancer patient studies with figitumumab at this time.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 28

Inclusion Criteria

Healthy male subjects and/or healthy female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive
Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).

Exclusion Criteria

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
12-lead ECG demonstrating QTc >450 msec at screening or other clinically significant abnormalities at screening.
History or family history of risk factors for QTc interval prolongation or torsades de pointes (eg, organic heart disease, congestive heart failure, hypokalemia, hypomagnesemia, congenital long QT syndrome, myocardial ischemia or infarction); family history of sudden death.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
20 mg/kg cohort	CP-751,871	-
20/20 mg/kg cohort	CP-751,871, moxifloxacin, saline	-
10 mg/kg cohort	CP-751,871	-

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax)	Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85
Area Under the Curve From Time Zero to the Last Time Point With Quantifiable Concentration (AUClast)	Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Plasma Clearance (CL)	Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Apparent Volume of Distribution (Vz)	Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Plasma Decay Half-Life (t1/2)	Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
QTc Using Fridericia's Correction Method (QTcF) After Receiving CP-751,871 at the 20/20 mg/kg Dose Level	Day 1 at 1 and 24 hours post-dose, Day 7, 28	QTcF is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, corrected for heart rate using Fridericia's correction

Secondary Outcome Measures

Name	Time	Method
QTcF After Receiving Moxifloxacin at the Historical Moxifloxacin Median Tmax of 3 Hours	baseline, 3 hours postdose
Serum Concentration of Insulin-like Growth Factor 1 (IGF-1)	Day 1 pre-dose (Baseline), 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85	IGF-1 is one of the IGF-axis related biomarkers. Part of the secondary objectives of the study was to explore the relationships of plasma CP-751,871 concentrations to such biomarkers. Cmax is the mean ± standard deviation (SD) concentration observed at the time of maximal change from baseline.
Serum Concentration of Free Insulin-like Growth Factor 1 (IGF-1)	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85	IGF-1 is one of the IGF-axis related biomarkers. Part of the secondary objectives of the study was to explore the relationships of plasma CP-751,871 concentrations to such biomarkers. Cmax is the mean ± standard deviation (SD) concentration observed at the time of maximal change from baseline.
Serum Concentration of Insulin-like Growth Factor 2 (IGF-2)	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85	IGF-2 is one of the IGF-axis related biomarkers. Part of the secondary objectives of the study was to explore the relationships of plasma CP-751,871 concentrations to such biomarkers. Cmax is the mean ± standard deviation (SD) concentration observed at the time of maximal change from baseline.
Serum Concentration of Insulin-like Growth Factor Binding Protein 3 (IGFBP-3)	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85	IGFBP-3 is one of the IGF-axis related biomarkers. Part of the secondary objectives of the study was to explore the relationships of plasma CP-751,871 concentrations to such biomarkers. Cmax is the mean ± standard deviation (SD) concentration observed at the time of maximal change from baseline.
Serum Concentration of Insulin	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85	Insulin is one of the IGF-axis related biomarkers. Part of the secondary objectives of the study was to explore the relationships of plasma CP-751,871 concentrations to such biomarkers. Cmax is the mean ± standard deviation (SD) concentration observed at the time of maximal change from baseline.
Serum Concentration of Fasting Glucose	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85	Glucose is one of the IGF-axis related biomarkers. Part of the secondary objectives of the study was to explore the relationships of plasma CP-751,871 concentrations to such biomarkers. Cmax is the mean ± standard deviation (SD) concentration observed at the time of maximal change from baseline.
Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Day 1 pre-dose, Day 15, 29, 57, 85	Number of participants who tested positive for ADA