Trial Outcomes & Findings for Study Of Axitinib In Combination With Cisplatin And Capecitabine In Patients With Advanced Gastric Cancer (NCT NCT00842244)

Last Updated: 2013-11-27

Results Overview

DLT = Grade (GR) 2 proteinuria; GR3 nonhematological toxicity (NHT) (excluding alopecia and those that can be controlled with appropriate treatment) for greater than or equal to (\>=)7 days, GR3 thrombocytopenia with active bleeding; GR \>=3 febrile neutropenia (NP) or NP infection; GR 3 or 4 nausea, vomiting or diarrhea despite anti-emetics, anti-diarrheals; GR4 NHT, thrombocytopenia, NP for \>=7 days; \>= 1/2 teaspoon per day hemoptysis; any treatment related toxicity with \>3 consecutive days of capecitabine or 5 consecutive days of axitinib missed doses per cycle; delayed toxicity recovery \>14 days.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

22 participants

Primary outcome timeframe

Baseline up to Day 21 of Cycle 1

Results posted on

2013-11-27

Participant Flow

Participant milestones

Participant milestones
Measure	Axitinib + Capecitabine + Cisplatin Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg per square meter (mg/m\^2) tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hours (hrs) on Day 1 of each cycle, in cycles of 21 days. Participants enrolled in pharmacokinetic (PK) expansion cohort at maximum tolerated dose (MTD) received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Overall Study STARTED	22
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Axitinib + Capecitabine + Cisplatin Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg per square meter (mg/m\^2) tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hours (hrs) on Day 1 of each cycle, in cycles of 21 days. Participants enrolled in pharmacokinetic (PK) expansion cohort at maximum tolerated dose (MTD) received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Overall Study Death	3
Overall Study Withdrawal by Subject	1
Overall Study Other	17

Baseline Characteristics

Study Of Axitinib In Combination With Cisplatin And Capecitabine In Patients With Advanced Gastric Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Axitinib + Capecitabine + Cisplatin n=22 Participants Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg per square meter (mg/m\^2) tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hours (hrs) on Day 1 of each cycle, in cycles of 21 days. Participants enrolled in pharmacokinetic (PK) expansion cohort at maximum tolerated dose (MTD) received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Age Continuous	59.3 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 21 of Cycle 1

Population: DLT analysis set: participants who received first cycle of study treatment and did not temporarily or permanently discontinue or miss more than 5 consecutive days of axitinib (AG-13736) or more than 3 consecutive days of capecitabine for reasons other than DLTs within first cycle.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=12 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)	3 participants

SECONDARY outcome

Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hrs post-axitinib dose on Cycle 1 (C1) Day -1 (D-1), C1D1; 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hrs post-capecitabine dose C1D1, C2D1; 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 hrs post-cisplatin infusion start C1D1, C2D1

Population: Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest. Here, 'n' signifies those participants who were evaluable for specified study drug's PK parameter alone or in combination.

Cmax for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Cmax for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-fluorouracil \[5-FU\], 5-deoxy-5-fluorouridine \[5-DFUR\] and 5-deoxy-5-fluorocytidine \[5-DFC\]) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1. Results for axitinib were normalized to axitinib 5 mg dose, results for capecitabine and its metabolites (5-FU, 5-DFUR and 5-DFC) were normalized to Cycle 1 Day 1 capecitabine dose and results for cisplatin were normalized to Cycle 1 Day 1 cisplatin dose.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=10 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU in presence of axitinib (n = 8)	90.97 nanogram/milliliter (ng/mL) Interval 54.59 to 151.59
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC alone (n = 8)	5891.29 nanogram/milliliter (ng/mL) Interval 4416.64 to 7858.31
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib alone (n = 10)	16.11 nanogram/milliliter (ng/mL) Interval 9.94 to 26.1
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib in combination with chemotherapy (n = 10)	24.33 nanogram/milliliter (ng/mL) Interval 15.01 to 39.43
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine alone (n = 8)	5255.62 nanogram/milliliter (ng/mL) Interval 3155.36 to 8753.85
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine in presence of axitinib (n = 8)	2274.80 nanogram/milliliter (ng/mL) Interval 1365.74 to 3788.95
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU alone (n = 8)	220.49 nanogram/milliliter (ng/mL) Interval 132.31 to 367.44
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR alone (n = 8)	5791.81 nanogram/milliliter (ng/mL) Interval 3871.8 to 8663.95
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR in presence of axitinib (n = 8)	3017.27 nanogram/milliliter (ng/mL) Interval 2017.03 to 4513.52
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC in presence of axitinib (n = 8)	3227.57 nanogram/milliliter (ng/mL) Interval 2419.68 to 4305.21
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin alone (n = 8)	1665.27 nanogram/milliliter (ng/mL) Interval 1407.48 to 1970.26
Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin in presence of axitinib (n = 8)	1865.07 nanogram/milliliter (ng/mL) Interval 1576.36 to 2206.66

SECONDARY outcome

Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hrs post-axitinib dose on C1D-1, C1D1; 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hrs post-capecitabine dose C1D1, C2D1; 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 hrs post-cisplatin infusion start C1D1, C2D1

Tmax for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Tmax for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR and 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=10 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib alone (n = 10)	3.98 hrs Interval 0.0 to 7.97
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib in combination with chemotherapy (n = 10)	4.00 hrs Interval 1.0 to 6.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine alone (n = 8)	2.45 hrs Interval 0.5 to 4.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine in presence of axitinib (n = 8)	3.12 hrs Interval 0.5 to 4.02
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU alone (n = 8)	2.50 hrs Interval 0.5 to 4.07
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU in presence of axitinib (n = 8)	2.62 hrs Interval 0.5 to 4.02
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR alone (n = 8)	2.50 hrs Interval 0.5 to 4.07
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR in presence of axitinib (n = 8)	2.62 hrs Interval 0.97 to 4.02
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC alone (n = 8)	2.50 hrs Interval 0.5 to 4.07
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC in presence of axitinib (n = 8)	3.09 hrs Interval 0.5 to 4.02
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin alone (n = 8)	2.00 hrs Interval 1.0 to 2.2
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin in presence of axitinib (n = 8)	1.02 hrs Interval 0.97 to 2.33

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hrs post-capecitabine dose C1D1, C2D1; 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 hrs post-cisplatin infusion start C1D1, C2D1

Population: Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Area under the plasma concentration time-curve from zero to the last measurable concentration (AUClast). AUClast for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR, 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1. Results for capecitabine and its metabolites (5-FU, 5-DFUR and 5-DFC) were normalized to Cycle 1 Day 1 capecitabine dose and results for cisplatin were normalized to Cycle 1 Day 1 cisplatin dose.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=8 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC in presence of axitinib	7983.14 nanogramhour/milliliter (nghr/mL) Interval 6520.93 to 9773.23
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine alone	7109.59 nanogramhour/milliliter (nghr/mL) Interval 4525.07 to 11170.27
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine in presence of axitinib	4194.97 nanogramhour/milliliter (nghr/mL) Interval 2669.99 to 6590.95
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU alone	332.37 nanogramhour/milliliter (nghr/mL) Interval 238.03 to 464.12
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU in presence of axitinib	176.81 nanogramhour/milliliter (nghr/mL) Interval 126.62 to 246.89
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR alone	9996.55 nanogramhour/milliliter (nghr/mL) Interval 8183.62 to 12211.1
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR in presence of axitinib	6683.33 nanogramhour/milliliter (nghr/mL) Interval 5471.27 to 8163.9
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC alone	10820.14 nanogramhour/milliliter (nghr/mL) Interval 8838.29 to 13246.37
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin alone	3814.93 nanogramhour/milliliter (nghr/mL) Interval 3463.52 to 4202.0
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin in presence of axitinib	3951.57 nanogramhour/milliliter (nghr/mL) Interval 3587.57 to 4352.5

SECONDARY outcome

Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hrs post-axitinib dose on C1D-1, C1D1

AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours. AUC (0-24) for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Results for axitinib were normalized to axitinib 5 mg dose.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=9 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] for Axitinib Axitinib alone	206.20 ng*hr/mL Interval 109.2 to 389.36
Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] for Axitinib Axitinib in combination with chemotherapy	265.89 ng*hr/mL Interval 140.81 to 502.08

SECONDARY outcome

Population: Pharmacokinetic parameter analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here, 'n' signifies those participants who were evaluable for specified study drug's PK parameter alone or in combination.

AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. AUC (0 - ∞) for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR and 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1. Results for axitinib were normalized to axitinib 5 mg dose, results for capecitabine and its metabolites (5-FU, 5-DFUR and 5-DFC) were normalized to Cycle 1 Day 1 capecitabine dose and results for cisplatin were normalized to Cycle 1 Day 1 cisplatin dose.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=9 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib in combination with chemotherapy (n = 9)	156.00 ng*hr/mL Interval 75.1 to 324.02
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib alone (n = 9)	147.04 ng*hr/mL Interval 70.79 to 305.42
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine alone (n = 6)	7140.62 ng*hr/mL Interval 4197.86 to 12146.29
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine in presence of axitinib (n = 6)	4213.72 ng*hr/mL Interval 2477.18 to 7167.6
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU alone (n = 3)	337.85 ng*hr/mL Interval 198.44 to 575.2
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU in presence of axitinib (n = 3)	261.95 ng*hr/mL Interval 153.86 to 445.98
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR alone (n = 4)	9568.70 ng*hr/mL Interval 6772.04 to 13520.28
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR in presence of axitinib (n = 4)	6966.07 ng*hr/mL Interval 4930.09 to 9842.84
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC alone (n = 5)	11587.97 ng*hr/mL Interval 7974.0 to 16839.87
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC in presence of axitinib (n = 5)	7787.39 ng*hr/mL Interval 5358.71 to 11316.78
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin alone (n = 7)	3979.07 ng*hr/mL Interval 3577.6 to 4425.59
Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin in presence of axitinib (n = 7)	3990.34 ng*hr/mL Interval 3587.74 to 4438.12

SECONDARY outcome

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half life for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Plasma decay half life for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR and 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=9 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine in presence of axitinib (n = 6)	0.89 hrs Standard Deviation 0.520
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin in presence of axitinib (n = 7)	1.61 hrs Standard Deviation 0.772
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU in presence of axitinib (n = 3)	1.05 hrs Standard Deviation 0.506
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR alone (n = 4)	0.96 hrs Standard Deviation 0.400
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFUR in presence of axitinib (n = 4)	0.77 hrs Standard Deviation 0.125
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC alone (n = 5)	0.98 hrs Standard Deviation 0.499
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-DFC in presence of axitinib (n = 5)	0.78 hrs Standard Deviation 0.147
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Cisplatin alone (n = 7)	1.25 hrs Standard Deviation 0.095
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib alone (n = 9)	5.76 hrs Standard Deviation 3.665
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Axitinib in combination with chemotherapy (n = 9)	3.50 hrs Standard Deviation 1.869
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin Capecitabine alone (n = 6)	0.71 hrs Standard Deviation 0.441
Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin 5-FU alone (n = 3)	1.11 hrs Standard Deviation 0.455

SECONDARY outcome

Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hrs post-axitinib dose on C1D-1, C1D1; 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hrs post-capecitabine dose on C1D1, C2D1

Population: Pharmacokinetic parameter analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' = participants evaluable for specified study drug's PK parameter alone or in combination. Results are not reported for capecitabine metabolites because CL/F could not be accurately estimated.

Clearance (CL) 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 fraction of the dose absorbed (F). Clearance is defined as the volume of blood from which drug can be completely removed per unit of time. CL/F for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. CL/F for capecitabine in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (capecitabine alone) on Cycle 2 Day 1.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=9 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Apparent Oral Clearance (CL/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Capecitabine in presence of axitinib (n = 6)	368.47 Liter/hr Interval 200.58 to 676.89
Apparent Oral Clearance (CL/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Axitinib alone (n = 9)	48.55 Liter/hr Interval 25.71 to 91.7
Apparent Oral Clearance (CL/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Axitinib in combination with chemotherapy (n = 9)	37.69 Liter/hr Interval 19.96 to 71.19
Apparent Oral Clearance (CL/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Capecitabine alone (n = 6)	217.60 Liter/hr Interval 118.45 to 399.74

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 hrs post-cisplatin infusion start on C1D1, C2D1

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It is defined as the volume of blood from which drug can be completely removed per unit of time. Clearance for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate) in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin alone) on Cycle 2 Day 1.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=7 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Clearance (CL) for Cisplatin Cisplatin alone	30.94 Liter/hr Interval 26.03 to 36.77
Clearance (CL) for Cisplatin Cisplatin in presence of axitinib	32.50 Liter/hr Interval 27.35 to 38.63

SECONDARY outcome

Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hrs post-axitinib dose on C1D-1, C1D1; 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hrs post-capecitabine dose on C1D1, C2D1

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 blood concentration of a drug. Vz/F is influenced by the fraction absorbed. Vz/F for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Vz/F for capecitabine in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (capecitabine alone) on Cycle 2 Day 1.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=9 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Apparent Volume of Distribution (Vz/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Axitinib alone (n = 9)	344.87 Liter Interval 202.24 to 588.09
Apparent Volume of Distribution (Vz/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Capecitabine alone (n = 6)	190.94 Liter Interval 89.08 to 409.3
Apparent Volume of Distribution (Vz/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Capecitabine in presence of axitinib (n = 6)	425.00 Liter Interval 198.27 to 911.02
Apparent Volume of Distribution (Vz/F) for Axitinib, Capecitabine and Capecitabine's Metabolites Axitinib in combination with chemotherapy (n = 9)	171.83 Liter Interval 100.77 to 293.01

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 hrs post-cisplatin infusion start on C1D1, C2D1

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 blood concentration of a drug. Clearance for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate) in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin alone) on Cycle 2 Day 1.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=7 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Volume of Distribution (Vz) for Cisplatin Cisplatin alone	55.35 Liter Interval 41.12 to 74.51
Volume of Distribution (Vz) for Cisplatin Cisplatin in presence of axitinib	70.32 Liter Interval 52.24 to 94.66

SECONDARY outcome

Timeframe: Day 1 of Cycle 1

Population: Results are not reported because data was reported in individual participant listing but not statistically summarized for the analysis.

Genetic variants of uridine diphosphate (UDP)- glucuronosyl transferase 1A1 (UGT1A1) gene which were assessed for genotyping included UGT1A1\*60, UGT1A1-3156, UGT1A1 Promoter thymine adenine (TA) repeat (UGT1A1\*28, UGT1A1\*36, UGT1A1\*37), UGT1A1\*6 and UGT1A1\*27.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to disease progression or withdrawal, assessed on Day 21 of every other cycle starting from Cycle 2 up to Day 784

Population: Efficacy analysis set included all enrolled participants who received at least 1 dose of study medication, had measurable disease at baseline (according to RECIST criteria version 1.0), and had at least 1 tumor assessment during study.

Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are those with disappearance of all target lesions. PR are those with at least 30 percent (%) decrease in sum of the longest dimensions of target lesions taking the baseline sum of the longest dimensions as a reference.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=22 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Percentage of Participants With Objective Response (OR)	36.36 percentage of participants Interval 17.2 to 59.34

SECONDARY outcome

Timeframe: Baseline up to disease progression or withdrawal, assessed on Day 21 of every other cycle starting from Cycle 2 up to Day 784

Population: Analysis set included a subset of efficacy analysis set who had confirmed objective tumor response.

Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response. CR = disappearance of all target lesions. PR = at least 30% decrease in sum of the longest dimensions of target lesions taking the baseline sum of the longest dimensions as a reference.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=8 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Duration of Response (DR)	9.07 months Interval 6.44 to 20.2

SECONDARY outcome

Timeframe: Baseline up to disease progression or withdrawal, assessed on Day 21 of every other cycle starting from Cycle 2 up to Day 784

Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death"). PD was a\>=20% increase in sum of the longest dimensions of target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=22 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Progression-Free Survival (PFS)	3.75 months Interval 2.92 to 9.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 21 of Cycle 1

MTD = highest dose at which no more than 30 percent (%) of 12 participants experience DLT during Cycle 1. DLT = GR2 proteinuria; GR3 NHT (excluding alopecia and those that can be controlled with appropriate treatment)for \>=7 days, GR3 thrombocytopenia with active bleeding; GR \>=3 febrile NP/NP infection; GR 3 or 4 nausea, vomiting or diarrhea despite anti-emetics, anti-diarrheals; GR4 NHT, thrombocytopenia, NP for \>=7 days; \>= 1/2 teaspoon per day hemoptysis; any treatment-related toxicity with \>3 consecutive days of capecitabine or 5 consecutive days of axitinib missed doses per cycle; delayed toxicity recovery \>14 days.

Outcome measures

Outcome measures
Measure	Axitinib + Capecitabine + Cisplatin (MTD Determination) n=12 Participants Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Cisplatin and Capecitabine	5 mg

Adverse Events

Axitinib + Capecitabine + Cisplatin

Serious events: 12 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Axitinib + Capecitabine + Cisplatin n=22 participants at risk Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg per square meter (mg/m\^2) tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hours (hrs) on Day 1 of each cycle, in cycles of 21 days. Participants enrolled in pharmacokinetic (PK) expansion cohort at maximum tolerated dose (MTD) received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Cardiac disorders Bradycardia	4.5% 1/22 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.
Gastrointestinal disorders Enterocolitis	4.5% 1/22 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	4.5% 1/22 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.
Gastrointestinal disorders Gastrointestinal perforation	4.5% 1/22 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.
Gastrointestinal disorders Nausea	4.5% 1/22 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.
Gastrointestinal disorders Vomiting	4.5% 1/22 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.
General disorders Disease progression	9.1% 2/22 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.
Metabolism and nutrition disorders Decreased appetite	4.5% 1/22 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 Headache	4.5% 1/22 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 Hypoaesthesia	4.5% 1/22 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.
Renal and urinary disorders Renal failure acute	4.5% 1/22 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.
Vascular disorders Aortic aneurysm rupture	4.5% 1/22 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.
Vascular disorders Hypertension	4.5% 1/22 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.
Vascular disorders Thrombosis	4.5% 1/22 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.
Gastrointestinal disorders Diarrhoea	4.5% 1/22 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.
Infections and infestations Pneumonia	4.5% 1/22 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.
Renal and urinary disorders Acute prerenal failure	4.5% 1/22 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.

Other adverse events

Other adverse events
Measure	Axitinib + Capecitabine + Cisplatin n=22 participants at risk Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg per square meter (mg/m\^2) tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hours (hrs) on Day 1 of each cycle, in cycles of 21 days. Participants enrolled in pharmacokinetic (PK) expansion cohort at maximum tolerated dose (MTD) received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.
Blood and lymphatic system disorders Anaemia	13.6% 3/22 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.
Blood and lymphatic system disorders Neutropenia	63.6% 14/22 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.
Blood and lymphatic system disorders Thrombocytopenia	54.5% 12/22 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.
Ear and labyrinth disorders Tinnitus	9.1% 2/22 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.
Endocrine disorders Hypothyroidism	45.5% 10/22 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.
Gastrointestinal disorders Abdominal distension	9.1% 2/22 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.
Gastrointestinal disorders Abdominal pain	22.7% 5/22 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.
Gastrointestinal disorders Abdominal pain upper	27.3% 6/22 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.
Gastrointestinal disorders Cheilitis	9.1% 2/22 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.
Gastrointestinal disorders Constipation	40.9% 9/22 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.
Gastrointestinal disorders Diarrhoea	54.5% 12/22 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.
Gastrointestinal disorders Dyspepsia	13.6% 3/22 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.
Gastrointestinal disorders Nausea	77.3% 17/22 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.
Infections and infestations Periodontitis	9.1% 2/22 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.
Gastrointestinal disorders Stomatitis	72.7% 16/22 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.
Gastrointestinal disorders Vomiting	31.8% 7/22 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.
General disorders Asthenia	18.2% 4/22 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.
General disorders Fatigue	77.3% 17/22 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.
General disorders Mucosal inflammation	9.1% 2/22 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.
General disorders Oedema	9.1% 2/22 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.
General disorders Pyrexia	9.1% 2/22 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.
Infections and infestations Oral candidiasis	9.1% 2/22 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.
Infections and infestations Upper respiratory tract infection	13.6% 3/22 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.
Investigations Alanine aminotransferase increased	9.1% 2/22 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.
Investigations Blood bilirubin increased	9.1% 2/22 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.
Investigations Blood creatinine increased	13.6% 3/22 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.
Investigations Haemoglobin decreased	13.6% 3/22 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.
Investigations Neutrophil count decreased	9.1% 2/22 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.
Investigations Weight decreased	13.6% 3/22 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.
Metabolism and nutrition disorders Decreased appetite	90.9% 20/22 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.
Metabolism and nutrition disorders Hyperglycaemia	13.6% 3/22 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.
Metabolism and nutrition disorders Hypokalaemia	18.2% 4/22 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.
Metabolism and nutrition disorders Hypomagnesaemia	13.6% 3/22 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.
Musculoskeletal and connective tissue disorders Back pain	13.6% 3/22 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.
Musculoskeletal and connective tissue disorders Flank pain	9.1% 2/22 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.1% 2/22 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	9.1% 2/22 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 Dysgeusia	13.6% 3/22 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 Headache	18.2% 4/22 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 Neuropathy peripheral	18.2% 4/22 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.
Psychiatric disorders Insomnia	9.1% 2/22 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.
Renal and urinary disorders Proteinuria	9.1% 2/22 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.
Respiratory, thoracic and mediastinal disorders Dysphonia	54.5% 12/22 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.
Respiratory, thoracic and mediastinal disorders Hiccups	22.7% 5/22 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.
Respiratory, thoracic and mediastinal disorders Productive cough	9.1% 2/22 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.
Skin and subcutaneous tissue disorders Alopecia	18.2% 4/22 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.
Skin and subcutaneous tissue disorders Dry skin	9.1% 2/22 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.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	54.5% 12/22 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.
Skin and subcutaneous tissue disorders Pigmentation disorder	13.6% 3/22 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.
Skin and subcutaneous tissue disorders Pruritus	18.2% 4/22 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.
Skin and subcutaneous tissue disorders Rash	13.6% 3/22 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.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	9.1% 2/22 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.
Vascular disorders Hypertension	72.7% 16/22 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.
Vascular disorders Hypotension	13.6% 3/22 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.
Gastrointestinal disorders Abdominal discomfort	9.1% 2/22 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

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

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