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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00926263
First received: June 21, 2009
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
Healthy Volunteers
Biological: CP-751,871
Biological: CP-751,871, moxifloxacin, saline
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 28
Study Start Date: July 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00926263

Locations
United States, Connecticut
Pfizer Investigational Site
New Haven, Connecticut, United States, 06511-5473
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00926263     History of Changes
Other Study ID Numbers: A4021037
Study First Received: June 21, 2009
Results First Received: January 18, 2013
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Pharmacokinetics
Pharmacodynamics
QTc interval prolongation

Additional relevant MeSH terms:
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Antibodies, Monoclonal
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014