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

• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85 ] [ Designated as safety issue: No ]
• Area Under the Curve From Time Zero to the Last Time Point With Quantifiable Concentration (AUClast) [ Time Frame: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85 ] [ Designated as safety issue: No ]
  Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
• Plasma Clearance (CL) [ Time Frame: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85 ] [ Designated as safety issue: No ]
  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) [ Time Frame: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85 ] [ Designated as safety issue: No ]
  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) [ Time Frame: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Day 1 at 1 and 24 hours post-dose, Day 7, 28 ] [ Designated as safety issue: Yes ]
  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

• Pharmacokinetic parameters of CP-751,871 [ Time Frame: baseline to 12 weeks post dose ] [ Designated as safety issue: No ]
• QTc using Fridericia's correction method at each postdose time point after receiving CP-751,871 at the 20/20 mg/kg dose level [ Time Frame: base line to 4 weeks post dose ] [ Designated as safety issue: Yes ]

• QTcF After Receiving Moxifloxacin at the Historical Moxifloxacin Median Tmax of 3 Hours [ Time Frame: baseline, 3 hours postdose ] [ Designated as safety issue: Yes ]
• Serum Concentration of Insulin-like Growth Factor 1 (IGF-1) [ Time Frame: Day 1 pre-dose (Baseline), 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85 ] [ Designated as safety issue: No ]
  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) [ Time Frame: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85 ] [ Designated as safety issue: No ]
  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) [ Time Frame: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85 ] [ Designated as safety issue: No ]
  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) [ Time Frame: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Day 1 pre-dose, Day 15, 29, 57, 85 ] [ Designated as safety issue: Yes ]
  Number of participants who tested positive for ADA

• QTcF after receiving moxifloxacin at the historical moxifloxacin median Tmax of 3 hours [ Time Frame: baeline to 3 hours ] [ Designated as safety issue: No ]
• Adverse events, and abnormalities in clinical safety laboratory tests and vital signs [ Time Frame: baseline to 12 weeks post dose ] [ Designated as safety issue: Yes ]
• Measurements of IGF-axis related biomarkers [ Time Frame: baseline to 12 weeks post dose ] [ Designated as safety issue: No ]
• Anti-drug antibodies against CP-751,871 in serum samples [ Time Frame: baseline to 12 weeks post dose ] [ Designated as safety issue: Yes ]

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

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.

• Biological: CP-751,871
  single dose, 1-hr IV infusion
• Biological: CP-751,871, moxifloxacin, saline
  Two doses at 20 mg/kg each on two consecutive days, each administered via 1-hr IV infusion

• Experimental: 10 mg/kg cohort
  Intervention: Biological: CP-751,871
• Experimental: 20 mg/kg cohort
  Intervention: Biological: CP-751,871
• Experimental: 20/20 mg/kg cohort
  Intervention: Biological: CP-751,871, moxifloxacin, saline

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.