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

A Phase 1, Open Label Study To Evaluate The Pharmacokinetics, Pharmacodynamics, And Effect On QT/QTc Interval For CP-751,871 Following Single Intravenous Administration To Healthy Adult Subjects

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

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: CP-751,871; Biological: CP-751,871, moxifloxacin, saline

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511-5473
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg/kg cohort	Biological: CP-751,871; single dose, 1-hr IV infusion
Experimental: 20 mg/kg cohort	Biological: CP-751,871; single dose, 1-hr IV infusion
Experimental: 20/20 mg/kg cohort	Biological: CP-751,871, moxifloxacin, saline; Two doses at 20 mg/kg each on two consecutive days, each administered via 1-hr IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Area under the plasma concentration time-curve from zero to the last measured 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
Plasma Clearance (CL)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85
Apparent Volume of Distribution (Vz)	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.	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 (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85
QTc Using Fridericia's Correction Method (QTcF) After Receiving CP-751,871 at the 20/20 mg/kg Dose Level	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	Day 1 at 1 and 24 hours post-dose, Day 7, 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Day 1 pre-dose (Baseline), 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85
Serum Concentration of Free Insulin-like Growth Factor 1 (IGF-1)	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.	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85
Serum Concentration of Insulin-like Growth Factor 2 (IGF-2)	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.	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85
Serum Concentration of Insulin-like Growth Factor Binding Protein 3 (IGFBP-3)	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.	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85
Serum Concentration of Insulin	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.	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85
Serum Concentration of Fasting Glucose	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.	Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85
Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Number of participants who tested positive for ADA	Day 1 pre-dose, Day 15, 29, 57, 85

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: June 21, 2009
• First Submitted That Met QC Criteria: June 21, 2009
• First Posted (Estimate): June 23, 2009

Study Record Updates

• Last Update Posted (Estimate): May 7, 2013
• Last Update Submitted That Met QC Criteria: March 27, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; QTc interval prolongation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin; Antibodies, Monoclonal
• Other Study ID Numbers: A4021037