Trial Outcomes & Findings for Evaluation Of Hepatic Impairment On AG-013736 Pharmacokinetics (NCT NCT00692341)
NCT ID: NCT00692341
Last Updated: 2012-04-11
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hours (hrs) post-dose
Results posted on
2012-04-11
Participant Flow
Participant milestones
| Measure |
Axitinib : Normal Hepatic Function
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation Of Hepatic Impairment On AG-013736 Pharmacokinetics
Baseline characteristics by cohort
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
47.4 years
STANDARD_DEVIATION 5.2 • n=5 Participants
|
52.5 years
STANDARD_DEVIATION 5.6 • n=7 Participants
|
54.3 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
51.4 years
STANDARD_DEVIATION 5.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hours (hrs) post-dosePopulation: Pharmacokinetic (PK) concentration population included all participants who were treated and had at least 1 concentration measurement.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
|
30.43 ng/mL
Geometric Coefficient of Variation 50.00
|
26.96 ng/mL
Geometric Coefficient of Variation 127.00
|
38.85 ng/mL
Geometric Coefficient of Variation 50.00
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest.
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
|
155.68 ng*hr/mL
Geometric Coefficient of Variation 63.00
|
121.96 ng*hr/mL
Geometric Coefficient of Variation 167.00
|
303.96 ng*hr/mL
Geometric Coefficient of Variation 44.00
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest.
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
|
148.43 ng*hr/mL
Geometric Coefficient of Variation 69.00
|
115.98 ng*hr/mL
Geometric Coefficient of Variation 180.00
|
295.23 ng*hr/mL
Geometric Coefficient of Variation 44.00
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
|
3.50 hr
Interval 2.0 to 4.0
|
2.75 hr
Interval 1.0 to 4.0
|
4.00 hr
Interval 1.5 to 4.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest.
Plasma elimination half-life is the time measured for the plasma concentration to decrease by one half.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Plasma Elimination Half-life (t1/2)
|
4.74 hr
Standard Deviation 3.77
|
3.61 hr
Standard Deviation 3.02
|
7.12 hr
Standard Deviation 6.49
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Apparent Oral Clearance (CL/F)
|
535.3 mL/min
Geometric Coefficient of Variation 63.0
|
683.3 mL/min
Geometric Coefficient of Variation 167.0
|
274.2 mL/min
Geometric Coefficient of Variation 44.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest.
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. Apparent volume of distribution after oral dose (Vz/F) is influenced by the oral bioavailability.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Apparent Volume of Distribution (Vz/F)
|
166.43 Liter (L)
Geometric Coefficient of Variation 52.00
|
162.65 Liter (L)
Geometric Coefficient of Variation 87.00
|
127.68 Liter (L)
Geometric Coefficient of Variation 67.00
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=5 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Fraction of Unbound Drug (fu)
|
0.004 Ratio
Geometric Coefficient of Variation 25.000
|
0.003 Ratio
Geometric Coefficient of Variation 50.000
|
0.004 Ratio
Geometric Coefficient of Variation 134.000
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
Clearance of an unbound drug is a measure of the rate at which an unbound drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. Unbound drug clearance is a quantitative measure of the rate at which an unbound drug substance is removed from the blood.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=5 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Unbound Apparent Oral Clearance (CLu/F)
|
132218.6 mL/min
Geometric Coefficient of Variation 56.0 • Interval 10000.0 to 16000.0
|
120883.5 mL/min
Geometric Coefficient of Variation 82.0 • Interval 9000.0 to
|
67143.1 mL/min
Geometric Coefficient of Variation 109.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
Volume of distribution of unbound drug is defined as the theoretical volume in which the total amount of unbound drug would need to be uniformly distributed to produce the desired plasma concentration of unbound drug. Unbound apparent volume of distribution after oral dose (Vzu/F) is influenced by the oral bioavailability.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=5 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Unbound Apparent Volume of Distribution (Vzu/F)
|
41108.6 L
Geometric Coefficient of Variation 57.0
|
42378.3 L
Geometric Coefficient of Variation 40.0
|
31268.8 L
Geometric Coefficient of Variation 121.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
AUC (0 - ∞)u = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) for unbound drug. It is obtained from AUCu (0 - t) plus AUCu (t - ∞).
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=5 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u]
|
0.63 ng*hr/mL
Geometric Coefficient of Variation 56.00
|
0.69 ng*hr/mL
Geometric Coefficient of Variation 82.00
|
1.24 ng*hr/mL
Geometric Coefficient of Variation 109.00
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClastu) for unbound drug.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=5 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu)
|
0.60 ng*hr/mL
Geometric Coefficient of Variation 61.00
|
0.67 ng*hr/mL
Geometric Coefficient of Variation 81.00
|
1.21 ng*hr/mL
Geometric Coefficient of Variation 106.00
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dosePopulation: PK concentration population included all participants who were treated and had at least 1 concentration measurement. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
Cmaxu is the highest measured unbound plasma concentration during the dosing interval.
Outcome measures
| Measure |
Axitinib : Normal Hepatic Function
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=5 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 Participants
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Unbound Maximum Observed Plasma Concentration (Cmaxu)
|
0.12 ng/mL
Geometric Coefficient of Variation 46.00
|
0.13 ng/mL
Geometric Coefficient of Variation 47.00
|
0.16 ng/mL
Geometric Coefficient of Variation 97.00
|
Adverse Events
Axitinib : Normal Hepatic Function
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Axitinib : Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Axitinib : Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Axitinib : Normal Hepatic Function
n=8 participants at risk
Single oral dose of axitinib (AG-013736) 5 milligrams (mg) immediate release tablets (IRT) on Day 1 to participants with normal hepatic function.
|
Axitinib : Mild Hepatic Impairment
n=8 participants at risk
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with mild hepatic impairment. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time international normalized ratio \[INR\], ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total mild hepatic impairment score range is 5 (mild) to 15 (severe).
|
Axitinib : Moderate Hepatic Impairment
n=8 participants at risk
Single oral dose of axitinib (AG-013736) 5 mg IRT on Day 1 to participants with moderate hepatic impairment. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time or prothrombin time INR, ascites and encephalopathy grade) on a scale of 1 (mild or none) to 3 (most severe). Total moderate hepatic impairment score range is 5 (mild) to 15 (severe).
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
12.5%
1/8
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/8
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/8
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Lethargy
|
37.5%
3/8
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/8
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/8
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
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