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

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00926263

Enrollment

Registered

2009-06-23

Start date

2009-07-31

Completion date

2010-05-31

Last updated

2013-05-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Keywords

Pharmacokinetics, Pharmacodynamics, QTc interval prolongation

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.

Interventions

BIOLOGICALCP-751,871

single dose, 1-hr IV infusion

BIOLOGICALCP-751,871, moxifloxacin, saline

Two doses at 20 mg/kg each on two consecutive days, each administered via 1-hr IV infusion

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
QTcF After Receiving Moxifloxacin at the Historical Moxifloxacin Median Tmax of 3 Hours	baseline, 3 hours postdose	—
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
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.

Countries

United States

Participant flow

Pre-assignment details

Study participants were planned to be assigned to 1 of 3 sequential dosing cohorts: CP-751,871 at 10 mg/kg; at 20 mg/kg; 2 doses of 20 mg/kg on consecutive days. Dosing was via intravenous (IV) administration. The third dosing cohort (2 doses of 20 mg/kg on consecutive days) did not enroll participants due to early termination of the study.

Participants by arm

Arm	Count
CP-751,871 10 mg/kg A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.	16
CP-751,871 20 mg/kg A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.	12
Total	28

Baseline characteristics

Characteristic	CP-751,871 20 mg/kg	Total	CP-751,871 10 mg/kg
Age Continuous	30.3 years STANDARD_DEVIATION 7.7	30.6 years STANDARD_DEVIATION 6.8	30.9 years STANDARD_DEVIATION 6.3
Race/Ethnicity, Customized Asian	1 participants	1 participants	0 participants
Race/Ethnicity, Customized Black	8 participants	18 participants	10 participants
Race/Ethnicity, Customized Other	0 participants	2 participants	2 participants
Race/Ethnicity, Customized White	3 participants	7 participants	4 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	12 Participants	28 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	9 / 16	12 / 12
serious Total, serious adverse events	0 / 16	0 / 12

Outcome results

Primary

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.

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

Population: All treated and evaluable participants (had measurements related to the PK parameter stated above).

Arm	Measure	Value (MEAN)	Dispersion
CP-751,871 10 mg/kg	Apparent Volume of Distribution (Vz)	84.89 mL/kg	Standard Deviation 13.731
CP-751,871 20 mg/kg	Apparent Volume of Distribution (Vz)	92.17 mL/kg	Standard Deviation 14.978

Primary

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)

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

Population: All treated participants.

Arm	Measure	Value (MEAN)	Dispersion
CP-751,871 10 mg/kg	Area Under the Curve From Time Zero to the Last Time Point With Quantifiable Concentration (AUClast)	80740 mg*h/L	Standard Deviation 14184
CP-751,871 20 mg/kg	Area Under the Curve From Time Zero to the Last Time Point With Quantifiable Concentration (AUClast)	184000 mg*h/L	Standard Deviation 27811

Primary

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

Population: All treated participants.

Arm	Measure	Value (MEAN)	Dispersion
CP-751,871 10 mg/kg	Maximum Observed Plasma Concentration (Cmax)	225.1 mg/L	Standard Deviation 54.175
CP-751,871 20 mg/kg	Maximum Observed Plasma Concentration (Cmax)	420.6 mg/L	Standard Deviation 62.175

Primary

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.

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

Population: All treated and evaluable participants (had measurements related to the PK parameter stated above).

Arm	Measure	Value (MEAN)	Dispersion
CP-751,871 10 mg/kg	Plasma Clearance (CL)	2.808 mL/day/kg	Standard Deviation 0.3804
CP-751,871 20 mg/kg	Plasma Clearance (CL)	2.353 mL/day/kg	Standard Deviation 0.4346

Primary

Plasma Decay Half-Life (t1/2)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

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

Population: All treated and evaluable participants (had measurements related to the PK parameter stated above).

Arm	Measure	Value (MEAN)	Dispersion
CP-751,871 10 mg/kg	Plasma Decay Half-Life (t1/2)	21.08 days	Standard Deviation 2.995
CP-751,871 20 mg/kg	Plasma Decay Half-Life (t1/2)	27.75 days	Standard Deviation 5.7969

Primary

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

Time frame: Day 1 at 1 and 24 hours post-dose, Day 7, 28

Population: Data not obtained due to early termination of the study.

Secondary

Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples

Number of participants who tested positive for ADA

Time frame: Day 1 pre-dose, Day 15, 29, 57, 85

Population: All treated participants.

Arm	Measure	Group	Value (NUMBER)
CP-751,871 10 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 1	0 number of participants
CP-751,871 10 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 57	0 number of participants
CP-751,871 10 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 15	0 number of participants
CP-751,871 10 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 85	0 number of participants
CP-751,871 10 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 29	0 number of participants
CP-751,871 20 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 85	0 number of participants
CP-751,871 20 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 15	0 number of participants
CP-751,871 20 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 29	0 number of participants
CP-751,871 20 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 57	0 number of participants
CP-751,871 20 mg/kg	Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples	Nominal Day 1	0 number of participants

Secondary

QTcF After Receiving Moxifloxacin at the Historical Moxifloxacin Median Tmax of 3 Hours

Time frame: baseline, 3 hours postdose

Population: Data not obtained due to early termination of the study.

Secondary

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.

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