Trial Outcomes & Findings for VEG113971: An Open-Label Study of the Effects of Ketoconazole or Esomeprazole on Pazopanib PK (NCT NCT01205230)
NCT ID: NCT01205230
Last Updated: 2012-05-22
Results Overview
Blood samples for pharmacokinetic (PK) analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter AUC(0-24) was determined by standard non-compartmental analysis using WinNonlin. Plasma AUC(0-24) is a measure of the amount of drug a participant has been exposed to in 24 hours.
COMPLETED
PHASE4
34 participants
Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
2012-05-22
Participant Flow
Participant milestones
| Measure |
Pazopanib, Followed by Pazopanib + Ketoconazole
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1, followed by ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib, Followed by Pazopanib + Esomeprazole
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1, followed by pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (approximately 3 hours after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|
|
Overall Study
STARTED
|
21
|
13
|
|
Overall Study
Combination Therapy
|
21
|
13
|
|
Overall Study
COMPLETED
|
16
|
13
|
|
Overall Study
NOT COMPLETED
|
5
|
0
|
Reasons for withdrawal
| Measure |
Pazopanib, Followed by Pazopanib + Ketoconazole
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1, followed by ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib, Followed by Pazopanib + Esomeprazole
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1, followed by pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (approximately 3 hours after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
VEG113971: An Open-Label Study of the Effects of Ketoconazole or Esomeprazole on Pazopanib PK
Baseline characteristics by cohort
| Measure |
Pazopanib, Followed by Pazopanib + Ketoconazole
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1, followed by ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib, Followed by Pazopanib + Esomeprazole
n=13 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1, followed by pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (approximately 3 hours after the evening meal) for 5 consecutive days during Period 2
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
Years
|
60.0 Years
STANDARD_DEVIATION 12.27 • n=93 Participants
|
57.9 Years
STANDARD_DEVIATION 13.09 • n=4 Participants
|
59.2 Years
STANDARD_DEVIATION 12.43 • n=27 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
1 participants
n=93 Participants
|
2 participants
n=4 Participants
|
3 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian - Central/South Asian Heritage
|
2 participants
n=93 Participants
|
0 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian Heritage
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
17 participants
n=93 Participants
|
10 participants
n=4 Participants
|
27 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.Population: Pharmacokinetic (PK) Population: all participants who underwent plasma PK sampling and had evaluable PK assay results from at least one analyte
Blood samples for pharmacokinetic (PK) analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter AUC(0-24) was determined by standard non-compartmental analysis using WinNonlin. Plasma AUC(0-24) is a measure of the amount of drug a participant has been exposed to in 24 hours.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=16 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Plasma Pazopanib Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC[0-24]) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
|
786 Hour*micrograms/milliliters (hr*mcg/mL)
Interval 632.0 to 976.0
|
1300 Hour*micrograms/milliliters (hr*mcg/mL)
Interval 1030.0 to 1620.0
|
848 Hour*micrograms/milliliters (hr*mcg/mL)
Interval 660.0 to 1090.0
|
512 Hour*micrograms/milliliters (hr*mcg/mL)
Interval 418.0 to 627.0
|
PRIMARY outcome
Timeframe: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.Population: PK Population
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. The concentration-time curve is the result of time points of blood sampling and its measured concentration of pazopanib in the plasma.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=16 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Plasma Maximum Observed Concentration (Cmax) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
|
40.7 mcg/mL
Interval 32.8 to 50.6
|
59.2 mcg/mL
Interval 45.1 to 77.6
|
48.9 mcg/mL
Interval 39.5 to 60.6
|
28.4 mcg/mL
Interval 23.8 to 33.9
|
PRIMARY outcome
Timeframe: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.Population: PK Population
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. Nominal data collection time points (TPs) were defined in the protocol; however, the actual data collection TP often differed slightly from the nominal TP for various reasons. This leads to medians and ranges that don't coincide with planned nominal data collection TPs.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=16 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Time of Occurrence of Cmax (Tmax) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
|
3.48 hours (hr)
Interval 2.0 to 24.0
|
3.48 hours (hr)
Interval 2.0 to 23.9
|
3 hours (hr)
Interval 1.9 to 7.8
|
3.9 hours (hr)
Interval 1.0 to 24.8
|
SECONDARY outcome
Timeframe: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained 24 hours after administration of pazopanib.Population: PK Population
Pazopanib plasma concentration-time data were analyzed by non-compartmental methods with WinNonlin. Calculations were based on the actual sampling times. From the plasma concentration-time data, the PK parameter C24 was determined.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=16 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Plasma Concentration at 24 Hours After Administration (C24) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
|
26.9 mcg/mL
Interval 21.5 to 33.6
|
48.7 mcg/mL
Interval 36.5 to 65.0
|
27.2 mcg/mL
Interval 20.4 to 36.4
|
17.3 mcg/mL
Interval 12.6 to 23.7
|
SECONDARY outcome
Timeframe: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.Population: PK Population. One participant from the Pazopanib + Ketoconazole treatment arm was not analyzed for GSK1071306 due to mishandling of PK samples during shipping. Only those participants providing samples were analyzed.
Blood samples for PK analysis of the metabolites of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter AUC(0-24) was determined by standard non-compartmental analysis using WinNonlin. Plasma AUC(0-24) is a measure of the amount of drug a participant has been exposed to in 24 hours.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=16 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Plasma AUC(0-24) for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1268992, n=21, 16, 12, 12
|
30.3 hr*mcg/mL
Interval 23.4 to 39.2
|
30.3 hr*mcg/mL
Interval 22.5 to 40.8
|
35.5 hr*mcg/mL
Interval 25.4 to 49.6
|
20.8 hr*mcg/mL
Interval 16.2 to 26.5
|
|
Plasma AUC(0-24) for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1268997, n=20, 13, 12, 12
|
17.4 hr*mcg/mL
Interval 13.4 to 22.7
|
6.67 hr*mcg/mL
Interval 4.97 to 8.94
|
21.6 hr*mcg/mL
Interval 14.2 to 33.0
|
11.2 hr*mcg/mL
Interval 7.54 to 16.7
|
|
Plasma AUC(0-24) for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1071306, n=21, 15, 12, 12
|
7.61 hr*mcg/mL
Interval 5.81 to 9.97
|
4.26 hr*mcg/mL
Interval 3.44 to 5.27
|
11.7 hr*mcg/mL
Interval 8.24 to 16.6
|
8.14 hr*mcg/mL
Interval 5.73 to 11.6
|
SECONDARY outcome
Timeframe: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.Population: PK Population
Blood samples for PK analysis of the metabolites of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. The concentration-time curve is the result of time points of blood sampling and its measured concentration of pazopanib in the plasma.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=16 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Plasma Cmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1268992
|
1.55 mcg/mL
Interval 1.19 to 2.03
|
1.52 mcg/mL
Interval 1.16 to 2.01
|
1.95 mcg/mL
Interval 1.48 to 2.57
|
1.13 mcg/mL
Interval 0.89 to 1.44
|
|
Plasma Cmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1268997
|
1.02 mcg/mL
Interval 0.73 to 1.45
|
0.31 mcg/mL
Interval 0.22 to 0.44
|
1.65 mcg/mL
Interval 1.19 to 2.27
|
0.84 mcg/mL
Interval 0.56 to 1.24
|
|
Plasma Cmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1071306
|
0.39 mcg/mL
Interval 0.29 to 0.51
|
0.22 mcg/mL
Interval 0.16 to 0.29
|
0.61 mcg/mL
Interval 0.43 to 0.86
|
0.42 mcg/mL
Interval 0.3 to 0.59
|
SECONDARY outcome
Timeframe: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.Population: PK Population
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. Nominal data collection time points (TPs) were defined in the protocol; however, the actual data collection TP often differed slightly from the nominal TP for various reasons. This leads to medians and ranges that don't coincide with planned nominal data collection TPs.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=16 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=12 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Tmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1268992
|
4 hr
Interval 2.0 to 24.3
|
24 hr
Interval 0.0 to 27.0
|
3 hr
Interval 1.1 to 5.8
|
3 hr
Interval 1.0 to 24.8
|
|
Tmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1268997
|
3.02 hr
Interval 2.0 to 8.0
|
13.4 hr
Interval 0.0 to 27.0
|
2.2 hr
Interval 1.1 to 6.1
|
2.4 hr
Interval 1.0 to 24.8
|
|
Tmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
GSK1071306
|
3.12 hr
Interval 2.0 to 8.9
|
24.1 hr
Interval 0.0 to 27.0
|
3.9 hr
Interval 2.0 to 7.9
|
6 hr
Interval 1.0 to 24.8
|
SECONDARY outcome
Timeframe: Day 5 of Period 2 (combination therapy). Blood samples were collected within 60 minutes prior to pazopanib administration and 1 and 2 hours after pazopanib administration.Population: PK Population
Blood samples for the determination of plasma ketoconazole concentrations were collected before (pre-dose \[within 60 minutes prior to pazopanib administration\]) and after the final pazopanib and ketoconazole dose (fifth dose) during Period 2 at the indicated time points, relative to pazopanib administration (at 1 and 2 hours after pazopanib administration). Blood samples were obtained via peripheral intravenous cannula or central line. Concentrations of ketoconazole were determined in plasma samples using the currently approved analytical methodology.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=16 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Plasma Ketoconazole Concentration at the Indicated Time Points
Pre-dose
|
0.53 mcg/mL
Interval 0.0 to 1.56
|
—
|
—
|
—
|
|
Plasma Ketoconazole Concentration at the Indicated Time Points
1 hr
|
4.21 mcg/mL
Interval 0.18 to 10.5
|
—
|
—
|
—
|
|
Plasma Ketoconazole Concentration at the Indicated Time Points
2 hr
|
4.82 mcg/mL
Interval 0.24 to 8.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) to a maximum of 4 weeks after the last dose of study drug was administered (on Study Day 12)Population: All Treated Population: all participants who were enrolled into the study and received at least one dose of study drug
AEs were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0. Grades range from 0 (no toxicity) to 4 (life-threatening or disabling). A Grade 3 AE is severe; defined as considerable interference with the participant's daily activities, medical intervention/therapy required, and hospitalization possible. A Grade 4 AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, and hospitalization probable.
Outcome measures
| Measure |
Pazopanib 400 mg QD
n=21 Participants
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=21 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=13 Participants
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=13 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Number of Participants With the Indicated Grade 3 or 4 Adverse Events (AEs)
Hypertension
|
1 participants
|
2 participants
|
0 participants
|
2 participants
|
|
Number of Participants With the Indicated Grade 3 or 4 Adverse Events (AEs)
Hypokalemia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 or 4 Adverse Events (AEs)
Hypophosphatemia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 or 4 Adverse Events (AEs)
Lymphopenia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) to a maximum of 4 weeks after the last dose of study drug was administered (on Study Day 12)Population: All Treated Population. Per protocol, a DLT could not occur during single-agent pazopanib administration in Period 1; thus, data were only collected and analyzed for those participants receiving pazopanib co-administered with either ketoconazole or esomeprazole in Period 2.
The following were considered DLTs only while participants were receiving pazopanib co-administered with either ketoconazole or esomeprazole: Grade 4 hematologic toxicities, excluding lymphopenia; and Grade 3/4 non-hematologic toxicities, excluding alopecia and nausea/vomiting/diarrhea for which adequate supportive therapy had not been instituted. Toxicities observed once co-administration of pazopanib with ketoconazole or esomeprazole was complete (after Day 5 of Period 2) could also be considered DLTs if judged to be relevant by the investigator and the GlaxoSmithKline Medical Monitor.
Outcome measures
| Measure |
Pazopanib 400 mg QD
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=21 Participants
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=13 Participants
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Number of Participants With the Indicated Event of Dose Limiting Toxicity (DLT)
|
—
|
2 participants
|
—
|
0 participants
|
Adverse Events
Pazopanib 400 mg QD
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
Pazopanib 800 mg QD
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pazopanib 400 mg QD
n=21 participants at risk
Pazopanib 400 milligrams (mg) (2x200 mg tablets) once daily (QD), for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 400 mg QD + Ketoconazole 400 mg QD
n=21 participants at risk
Ketoconazole 400 mg (2x200 mg tablets) QD in combination with pazopanib 400 mg (2x200 mg tablets) QD for 5 consecutive days in the morning during Period 2
|
Pazopanib 800 mg QD
n=13 participants at risk
Pazopanib 800 mg (4x200 mg tablets) QD, for at least 7 consecutive days in the morning during Period 1
|
Pazopanib 800 mg QD + Esomeprazole 40 mg QD
n=13 participants at risk
Pazopanib 800 mg (4x200 mg tablets) QD in the morning in combination with esomeprazole 40 mg (1x40 mg capsule) QD in the evening (administered 1 hour after the evening meal) for 5 consecutive days during Period 2
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
23.8%
5/21
|
9.5%
2/21
|
7.7%
1/13
|
15.4%
2/13
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
3/21
|
19.0%
4/21
|
7.7%
1/13
|
0.00%
0/13
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
3/21
|
9.5%
2/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Gastrointestinal disorders
Oral Discomfort
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/21
|
0.00%
0/21
|
0.00%
0/13
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
4.8%
1/21
|
19.0%
4/21
|
0.00%
0/13
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/21
|
23.8%
5/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/21
|
14.3%
3/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/21
|
9.5%
2/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/21
|
9.5%
2/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/21
|
9.5%
2/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Nervous system disorders
Headache
|
9.5%
2/21
|
19.0%
4/21
|
7.7%
1/13
|
0.00%
0/13
|
|
Nervous system disorders
Dizziness
|
4.8%
1/21
|
9.5%
2/21
|
0.00%
0/13
|
7.7%
1/13
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
4.8%
1/21
|
0.00%
0/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/21
|
0.00%
0/21
|
0.00%
0/13
|
7.7%
1/13
|
|
Investigations
Blood Bilirubin Increased
|
4.8%
1/21
|
9.5%
2/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Blood Creatinine Increased
|
0.00%
0/21
|
14.3%
3/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Investigations
Blood Amylase Increased
|
0.00%
0/21
|
9.5%
2/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Activated Partial Thromboplastin Time Prolonged
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Investigations
Alanine Aminotransferase Increased
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Investigations
Blood Lactate Dehydrogenase Increased
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Investigations
Lipase Increased
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Investigations
White Blood Cell Count Decreased
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Vascular disorders
Hypertension
|
14.3%
3/21
|
14.3%
3/21
|
0.00%
0/13
|
23.1%
3/13
|
|
General disorders
Asthenia
|
4.8%
1/21
|
0.00%
0/21
|
0.00%
0/13
|
0.00%
0/13
|
|
General disorders
Fatigue
|
4.8%
1/21
|
0.00%
0/21
|
0.00%
0/13
|
15.4%
2/13
|
|
General disorders
Hunger
|
4.8%
1/21
|
0.00%
0/21
|
0.00%
0/13
|
0.00%
0/13
|
|
General disorders
Mucosal Inflammation
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
General disorders
Pyrexia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
General disorders
Gait Disturbance
|
0.00%
0/21
|
0.00%
0/21
|
0.00%
0/13
|
7.7%
1/13
|
|
General disorders
Edema
|
0.00%
0/21
|
0.00%
0/21
|
0.00%
0/13
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Endocrine disorders
Adrenal Insufficiency
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Psychiatric disorders
Depression
|
0.00%
0/21
|
9.5%
2/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Night Sweats
|
0.00%
0/21
|
4.8%
1/21
|
0.00%
0/13
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/21
|
0.00%
0/21
|
0.00%
0/13
|
7.7%
1/13
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER