Trial Outcomes & Findings for A Pharmacokinetic And QT Study Of CP-751,871 In Healthy Subjects (NCT NCT00926263)
NCT ID: NCT00926263
Last Updated: 2013-05-07
Results Overview
TERMINATED
PHASE1
28 participants
Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85
2013-05-07
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
12
|
|
Overall Study
COMPLETED
|
16
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Pharmacokinetic And QT Study Of CP-751,871 In Healthy Subjects
Baseline characteristics by cohort
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
30.9 years
STANDARD_DEVIATION 6.3 • n=5 Participants
|
30.3 years
STANDARD_DEVIATION 7.7 • n=7 Participants
|
30.6 years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
10 participants
n=5 Participants
|
8 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85Population: All treated participants.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
|
225.1 mg/L
Standard Deviation 54.175
|
420.6 mg/L
Standard Deviation 62.175
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85Population: All treated participants.
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Area Under the Curve From Time Zero to the Last Time Point With Quantifiable Concentration (AUClast)
|
80740 mg*h/L
Standard Deviation 14184
|
184000 mg*h/L
Standard Deviation 27811
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85Population: All treated and evaluable participants (had measurements related to the PK parameter stated above).
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=13 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Plasma Clearance (CL)
|
2.808 mL/day/kg
Standard Deviation 0.3804
|
2.353 mL/day/kg
Standard Deviation 0.4346
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85Population: All treated and evaluable participants (had measurements related to the PK parameter stated above).
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.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=13 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz)
|
84.89 mL/kg
Standard Deviation 13.731
|
92.17 mL/kg
Standard Deviation 14.978
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and 1 hour post-dose, Day 2 (24 hours post-dose), 8, 15, 22, 29, 43, 57, 71 and 85Population: All treated and evaluable participants (had measurements related to the PK parameter stated above).
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=13 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Plasma Decay Half-Life (t1/2)
|
21.08 days
Standard Deviation 2.9950
|
27.75 days
Standard Deviation 5.7969
|
PRIMARY outcome
Timeframe: Day 1 at 1 and 24 hours post-dose, Day 7, 28Population: Data not obtained due to early termination of the study.
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
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, 3 hours postdosePopulation: Data not obtained due to early termination of the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 pre-dose (Baseline), 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85Population: All treated participants who had at least 1 postdose concentration measurement.
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.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Serum Concentration of Insulin-like Growth Factor 1 (IGF-1)
Baseline
|
138 ng/mL
Standard Deviation 33
|
128 ng/mL
Standard Deviation 23
|
|
Serum Concentration of Insulin-like Growth Factor 1 (IGF-1)
at Cmax
|
566 ng/mL
Standard Deviation 142
|
610 ng/mL
Standard Deviation 143
|
SECONDARY outcome
Timeframe: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85Population: All treated participants who had at least 1 postdose concentration measurement.
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.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Serum Concentration of Free Insulin-like Growth Factor 1 (IGF-1)
Baseline
|
17.2 ng/mL
Standard Deviation 6.6
|
13.9 ng/mL
Standard Deviation 5.6
|
|
Serum Concentration of Free Insulin-like Growth Factor 1 (IGF-1)
at Cmax
|
143 ng/mL
Standard Deviation 45
|
168 ng/mL
Standard Deviation 43
|
SECONDARY outcome
Timeframe: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85Population: All treated participants who had at least 1 postdose concentration measurement.
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.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Serum Concentration of Insulin-like Growth Factor 2 (IGF-2)
Baseline
|
1550 ng/mL
Standard Deviation 440
|
1476 ng/mL
Standard Deviation 229
|
|
Serum Concentration of Insulin-like Growth Factor 2 (IGF-2)
at Cmax
|
2039 ng/mL
Standard Deviation 582
|
1909 ng/mL
Standard Deviation 275
|
SECONDARY outcome
Timeframe: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85Population: All treated participants who had at least 1 postdose concentration measurement.
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.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Serum Concentration of Insulin-like Growth Factor Binding Protein 3 (IGFBP-3)
Baseline
|
2041 ng/mL
Standard Deviation 546
|
1978 ng/mL
Standard Deviation 496
|
|
Serum Concentration of Insulin-like Growth Factor Binding Protein 3 (IGFBP-3)
at Cmax
|
4945 ng/mL
Standard Deviation 1035
|
5819 ng/mL
Standard Deviation 1310
|
SECONDARY outcome
Timeframe: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85Population: All treated participants who had at least 1 postdose concentration measurement.
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.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Serum Concentration of Insulin
Baseline
|
5.13 mIU/mL
Standard Deviation 3.17
|
4.07 mIU/mL
Standard Deviation 3.30
|
|
Serum Concentration of Insulin
at Cmax
|
37.6 mIU/mL
Standard Deviation 23.8
|
40.0 mIU/mL
Standard Deviation 34.5
|
SECONDARY outcome
Timeframe: Day 1 pre-dose, 1 hour post dose, Day 2 (24 hours post-dose), Day 8, 15, 22, 29, 43, 57, 71, 85Population: All treated participants who had at least 1 postdose concentration measurement.
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.
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Serum Concentration of Fasting Glucose
Baseline
|
87.7 mg/dL
Standard Deviation 6.4
|
87.3 mg/dL
Standard Deviation 5.1
|
|
Serum Concentration of Fasting Glucose
at Cmax
|
104 mg/dL
Standard Deviation 21
|
101 mg/dL
Standard Deviation 16
|
SECONDARY outcome
Timeframe: Day 1 pre-dose, Day 15, 29, 57, 85Population: All treated participants.
Number of participants who tested positive for ADA
Outcome measures
| Measure |
CP-751,871 10 mg/kg
n=16 Participants
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 Participants
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples
Nominal Day 1
|
0 number of participants
|
0 number of participants
|
|
Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples
Nominal Day 15
|
0 number of participants
|
0 number of participants
|
|
Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples
Nominal Day 29
|
0 number of participants
|
0 number of participants
|
|
Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples
Nominal Day 57
|
0 number of participants
|
0 number of participants
|
|
Anti-drug Antibodies (ADA) Against CP-751,871 in Serum Samples
Nominal Day 85
|
0 number of participants
|
0 number of participants
|
Adverse Events
CP-751,871 10 mg/kg
CP-751,871 20 mg/kg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
CP-751,871 10 mg/kg
n=16 participants at risk
A single dose of CP-751,871 at 10 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
CP-751,871 20 mg/kg
n=12 participants at risk
A single dose of CP-751,871 at 20 mg/kg following an 8 hour fast, administered via 1-hour IV infusion.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.00%
0/16
|
8.3%
1/12
|
|
Ear and labyrinth disorders
Cerumen impaction
|
6.2%
1/16
|
0.00%
0/12
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.00%
0/16
|
8.3%
1/12
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/16
|
8.3%
1/12
|
|
Ear and labyrinth disorders
Tinnitus
|
18.8%
3/16
|
0.00%
0/12
|
|
Eye disorders
Conjunctivitis allergic
|
0.00%
0/16
|
8.3%
1/12
|
|
Eye disorders
Dry eye
|
0.00%
0/16
|
75.0%
9/12
|
|
Eye disorders
Keratoconjunctivitis sicca
|
0.00%
0/16
|
8.3%
1/12
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/16
|
75.0%
9/12
|
|
Eye disorders
Vision blurred
|
6.2%
1/16
|
0.00%
0/12
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/16
|
8.3%
1/12
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/16
|
8.3%
1/12
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
2/16
|
8.3%
1/12
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/16
|
8.3%
1/12
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/16
|
8.3%
1/12
|
|
Gastrointestinal disorders
Hyperchlorhydria
|
0.00%
0/16
|
8.3%
1/12
|
|
Gastrointestinal disorders
Nausea
|
12.5%
2/16
|
8.3%
1/12
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/16
|
16.7%
2/12
|
|
General disorders
Asthenia
|
0.00%
0/16
|
8.3%
1/12
|
|
General disorders
Chest discomfort
|
0.00%
0/16
|
8.3%
1/12
|
|
General disorders
Chest pain
|
6.2%
1/16
|
0.00%
0/12
|
|
General disorders
Fatigue
|
6.2%
1/16
|
25.0%
3/12
|
|
General disorders
Pyrexia
|
0.00%
0/16
|
8.3%
1/12
|
|
Infections and infestations
Bronchitis
|
6.2%
1/16
|
0.00%
0/12
|
|
Infections and infestations
Chlamydial infection
|
0.00%
0/16
|
8.3%
1/12
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/16
|
16.7%
2/12
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/16
|
8.3%
1/12
|
|
Infections and infestations
Periorbital cellulitis
|
6.2%
1/16
|
0.00%
0/12
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/16
|
8.3%
1/12
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/16
|
8.3%
1/12
|
|
Injury, poisoning and procedural complications
Head injury
|
6.2%
1/16
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
6.2%
1/16
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/16
|
8.3%
1/12
|
|
Injury, poisoning and procedural complications
Thermal burn
|
6.2%
1/16
|
0.00%
0/12
|
|
Investigations
Audiogram abnormal
|
12.5%
2/16
|
0.00%
0/12
|
|
Investigations
Echocardiogram abnormal
|
6.2%
1/16
|
0.00%
0/12
|
|
Investigations
Heart rate irregular
|
6.2%
1/16
|
0.00%
0/12
|
|
Investigations
Schirmer's test abnormal
|
6.2%
1/16
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/16
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/16
|
16.7%
2/12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/16
|
16.7%
2/12
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.2%
1/16
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/16
|
8.3%
1/12
|
|
Nervous system disorders
Dizziness
|
12.5%
2/16
|
0.00%
0/12
|
|
Nervous system disorders
Headache
|
18.8%
3/16
|
25.0%
3/12
|
|
Nervous system disorders
Paraesthesia
|
6.2%
1/16
|
0.00%
0/12
|
|
Nervous system disorders
Somnolence
|
12.5%
2/16
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
1/16
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/16
|
16.7%
2/12
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/16
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/16
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/16
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Hair growth abnormal
|
6.2%
1/16
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
6.2%
1/16
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER