Trial Outcomes & Findings for Evaluation Of The Efficacy Of The Combination Of Axitinib With Pemetrexed And Cisplatin In The Treatment Of Non-Squamous Non-Small Cell Lung Cancer (NCT NCT00768755)

Last Updated: 2015-10-28

Results Overview

Time in months from the date of randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus minus the date of randomization plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]); death was determined from AE data (where the outcome was "Death") or from the end of study data.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

180 participants

Primary outcome timeframe

Phase 2 baseline until the date of first documented progression or death due to any cause or initiation of subsequent anticancer therapy, assessed every 6 weeks up to 84 weeks

Results posted on

2015-10-28

Participant Flow

Participant milestones

Participant milestones
Measure	Axitinib + Pemetrexed/Cisplatin (Phase 1) Lead-in axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily (BID) from Day -5, -4 or -3 till Day 18 of Cycle 1 then continuously from Day 3 of Cycle 2 along with pemetrexed 500 milligram per square meter (mg/m\^2) infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable adverse events (AEs), or participant withdrawal.	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Phase 1 STARTED	10	0	0	0
Phase 1 COMPLETED	0	0	0	0
Phase 1 NOT COMPLETED	10	0	0	0
Phase 2 STARTED	0	55	58	57
Phase 2 Treated	0	55	58	55
Phase 2 COMPLETED	0	0	0	0
Phase 2 NOT COMPLETED	0	55	58	57

Reasons for withdrawal

Reasons for withdrawal
Measure	Axitinib + Pemetrexed/Cisplatin (Phase 1) Lead-in axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily (BID) from Day -5, -4 or -3 till Day 18 of Cycle 1 then continuously from Day 3 of Cycle 2 along with pemetrexed 500 milligram per square meter (mg/m\^2) infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable adverse events (AEs), or participant withdrawal.	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Phase 1 Death	6	0	0	0
Phase 1 Other	4	0	0	0
Phase 2 Death	0	37	48	31
Phase 2 Protocol Violation	0	2	0	1
Phase 2 Lost to Follow-up	0	1	1	4
Phase 2 Withdrawal by Subject	0	1	0	1
Phase 2 Other	0	1	2	4
Phase 2 Study Terminated by Sponsor	0	13	7	14
Phase 2 Randomized but not treated	0	0	0	2

Baseline Characteristics

Evaluation Of The Efficacy Of The Combination Of Axitinib With Pemetrexed And Cisplatin In The Treatment Of Non-Squamous Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Axitinib + Pemetrexed/Cisplatin (Phase 1) n=10 Participants Lead-in axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily (BID) from Day -5, -4 or -3 till Day 18 of Cycle 1 then continuously from Day 3 of Cycle 2 along with pemetrexed 500 milligram per square meter (mg/m\^2) infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable adverse events (AEs), or participant withdrawal.	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=58 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=57 Participants Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Total n=180 Participants Total of all reporting groups
Age, Customized Less Than 65 Years	5 participants n=5 Participants	35 participants n=7 Participants	34 participants n=5 Participants	43 participants n=4 Participants	117 participants n=21 Participants
Age, Customized Greater Than or Equal to 65 Years	5 participants n=5 Participants	20 participants n=7 Participants	24 participants n=5 Participants	14 participants n=4 Participants	63 participants n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	21 Participants n=7 Participants	21 Participants n=5 Participants	20 Participants n=4 Participants	63 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	34 Participants n=7 Participants	37 Participants n=5 Participants	37 Participants n=4 Participants	117 Participants n=21 Participants

PRIMARY outcome

Timeframe: Phase 2 baseline until the date of first documented progression or death due to any cause or initiation of subsequent anticancer therapy, assessed every 6 weeks up to 84 weeks

Population: Full analysis (FA) population, included all participants randomized with study medication assignment designated according to initial randomization, regardless of whether participants received study medication or received a different drug from that to which they were randomized.

Outcome measures

Outcome measures
Measure	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=58 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=57 Participants Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Progression-Free Survival (PFS)	8.0 months Interval 6.7 to 10.0	8.1 months Interval 6.8 to 9.9	7.1 months Interval 5.8 to 9.4

SECONDARY outcome

Timeframe: Baseline until death or collected bimonthly following discontinuation of study treatment until at least 1 year after randomization of the last participant

Population: FA population, included all participants randomized with study medication assignment designated according to initial randomization, regardless of whether participants received study medication or received a different drug from that to which they were randomized.

Time in months from the date of randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 30.4. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death).

Outcome measures

Outcome measures
Measure	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=58 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=57 Participants Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Overall Survival (OS)	17.0 months Interval 12.6 to 22.5	14.7 months Interval 11.5 to 18.1	15.9 months Interval 11.1 to Upper limit of confidence interval (C.I.) was not estimable due to insufficient events as there were few data points.

SECONDARY outcome

Timeframe: Phase 2 baseline until the date of first documented progression or discontinuation from the study due to any cause or initiation of subsequent anticancer therapy, assessed every 6 weeks up to 84 weeks

Percentage of participants with OR based assessment of confirmed complete response (CR)/confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors(RECIST).Confirmed responses: those persist on repeat imaging study at least 4 weeks after initial documentation of response.CR: disappearance of all lesions (target/non target) and no appearance of new lesions.PR: those with at least 30 % decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions,without progression of non target lesions and no appearance of new lesions.

Outcome measures

Outcome measures
Measure	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=58 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=57 Participants Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Percentage of Participants With Objective Response (OR)	45.5 percentage of participants Interval 32.0 to 59.4	39.7 percentage of participants Interval 27.0 to 53.4	26.3 percentage of participants Interval 15.5 to 39.7

SECONDARY outcome

Population: Subgroup of participants from the FA population with a confirmed objective tumor response (CR or PR).

Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause, whichever occurs first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cause 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.

Outcome measures

Outcome measures
Measure	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=25 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=23 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=15 Participants Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Duration of Response (DR)	7.82 months Interval 5.6 to 11.4	6.73 months Interval 5.0 to 7.8	7.10 months Interval 4.2 to 24.7

SECONDARY outcome

Timeframe: Phase 2 baseline (Cycle1/Day1), Cycle1/Day8, then Day 1 and 8 of each cycle of chemotherapy (C) up to CycleC6, Day 1 of each cycle of single-agent phase (A) up to CycleA8 and end of treatment (EOT)

Population: FA population; 'N' (number of participants analyzed) signifies participants evaluable for this measure and 'n' is number of participants analyzed at specific time point for each treatment arm respectively.

Symptom severity score is comprised of average of 13 MDASI core items (pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting, numbness or tingling) and ranges from 0 to 10. Participants were asked to rate severity of each symptom at their worst in last 24 hours; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Lower scores indicated better outcome.

Outcome measures

Outcome measures
Measure	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=53 Participants Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Phase 2 baseline (CycleC1/Day 1), (n= 55, 55, 53)	1.75 units on a scale Interval 1.32 to 2.18	2.09 units on a scale Interval 1.67 to 2.5	1.80 units on a scale Interval 1.33 to 2.27
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC1/Day 8, (n= 49, 49, 50)	1.55 units on a scale Interval 1.09 to 2.02	0.36 units on a scale Interval 0.0 to 0.72	0.95 units on a scale Interval 0.56 to 1.34
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC2/Day1 (n= 51, 51, 41)	0.12 units on a scale Interval -0.26 to 0.49	-0.05 units on a scale Interval -0.46 to 0.35	0.39 units on a scale Interval 0.01 to 0.77
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC2/Day8 (n= 39, 38, 34)	1.52 units on a scale Interval 0.98 to 2.06	0.39 units on a scale Interval -0.14 to 0.92	0.69 units on a scale Interval 0.24 to 1.13
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC3/Day1 (n= 45, 47, 39)	0.57 units on a scale Interval 0.16 to 0.97	0.29 units on a scale Interval -0.13 to 0.71	0.32 units on a scale Interval -0.15 to 0.79
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC3/Day8 (n= 38, 35, 32)	1.33 units on a scale Interval 0.75 to 1.92	0.87 units on a scale Interval 0.18 to 1.56	1.15 units on a scale Interval 0.61 to 1.68
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC4/Day1 (n= 43, 43, 38)	0.85 units on a scale Interval 0.28 to 1.42	0.48 units on a scale Interval -0.06 to 1.02	0.37 units on a scale Interval -0.05 to 0.79
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC4/Day8 (n= 33, 33, 27)	1.37 units on a scale Interval 0.64 to 2.09	0.90 units on a scale Interval 0.3 to 1.51	1.48 units on a scale Interval 0.77 to 2.19
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC5/Day1 (n= 35, 34, 29)	0.59 units on a scale Interval 0.05 to 1.12	0.48 units on a scale Interval -0.17 to 1.12	0.72 units on a scale Interval 0.25 to 1.18
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC5/Day8 (n= 29, 26, 25)	1.19 units on a scale Interval 0.38 to 2.0	0.82 units on a scale Interval 0.1 to 1.55	1.16 units on a scale Interval 0.46 to 1.87
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC6/Day1 (n= 27, 28, 28)	0.67 units on a scale Interval 0.04 to 1.3	0.42 units on a scale Interval -0.22 to 1.06	0.67 units on a scale Interval 0.11 to 1.23
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleC6/Day8 (n= 25, 25, 21)	1.44 units on a scale Interval 0.71 to 2.17	0.85 units on a scale Interval 0.23 to 1.47	1.28 units on a scale Interval 0.48 to 2.08
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA1/Day1 (n= 35, 33, 21)	0.63 units on a scale Interval 0.27 to 0.99	0.24 units on a scale Interval -0.32 to 0.79	0.68 units on a scale Interval -0.09 to 1.45
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA2/Day1 (n= 32, 30, 14)	0.36 units on a scale Interval -0.11 to 0.83	-0.01 units on a scale Interval -0.55 to 0.54	0.14 units on a scale Interval -0.49 to 0.77
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA3/Day1 (n= 27, 26, 10)	0.25 units on a scale Interval -0.3 to 0.79	0.01 units on a scale Interval -0.63 to 0.65	0.12 units on a scale Interval -0.38 to 0.63
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA4/Day1 (n= 22, 25, 0)	0.03 units on a scale Interval -0.65 to 0.7	0.07 units on a scale Interval -0.56 to 0.7	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA5/Day1 (n= 17, 23, 12)	0.19 units on a scale Interval -0.78 to 1.16	-0.12 units on a scale Interval -0.73 to 0.48	0.30 units on a scale Interval -0.37 to 0.96
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA6/Day1 (n= 17, 16, 10)	0.10 units on a scale Interval -0.56 to 0.77	-0.23 units on a scale Interval -1.21 to 0.76	0.14 units on a scale Interval -0.83 to 1.11
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA7/Day1 (n= 15, 15, 0)	-0.26 units on a scale Interval -0.99 to 0.47	-0.33 units on a scale Interval -1.37 to 0.7	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA8/Day1 (n= 15, 14, 10)	-0.28 units on a scale Interval -0.91 to 0.35	0.30 units on a scale Interval -0.76 to 1.36	0.02 units on a scale Interval -1.15 to 1.2
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA9/Day1 (n= 13, 11, 0)	-0.46 units on a scale Interval -1.29 to 0.38	0.34 units on a scale Interval -0.51 to 1.19	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at CycleA10/Day1 (n= 0, 10, 0)	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.	0.61 units on a scale Interval -0.38 to 1.59	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score Change at EOT (n= 40, 35, 31)	0.66 units on a scale Interval 0.12 to 1.2	1.02 units on a scale Interval 0.4 to 1.63	0.99 units on a scale Interval 0.33 to 1.64

SECONDARY outcome

Timeframe: Phase 2 baseline (Cycle1/Day1), Cycle1/Day8, then Day 1 and 8 of each cycle of chemotherapy (C) up to CycleC6, Day 1 of each cycle of single-agent phase (A) up to CycleA8 and EOT

Symptom interference score is comprised of average of 6 function items from MDASI core (general activity, mood, work, relations with others, walking, and enjoyment of life) and ranges from 0 to 10. Participants were asked to rate how much symptoms have interfered in last 24 hours; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Lower scores indicated better outcome.

Outcome measures

Outcome measures
Measure	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=55 Participants Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=53 Participants Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Phase 2 baseline (CycleC1/Day 1), (n= 55, 55, 53)	2.36 units on a scale Interval 1.64 to 3.08	2.97 units on a scale Interval 2.27 to 3.68	2.64 units on a scale Interval 1.92 to 3.37
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC1/Day 8, (n= 49, 49, 50)	1.48 units on a scale Interval 0.8 to 2.16	-0.03 units on a scale Interval -0.75 to 0.68	0.81 units on a scale Interval 0.27 to 1.36
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC2/Day1 (n= 51, 51, 41)	0.27 units on a scale Interval -0.21 to 0.75	-0.24 units on a scale Interval -0.76 to 0.29	0.30 units on a scale Interval -0.25 to 0.84
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC2/Day8 (n= 39, 38, 34)	2.00 units on a scale Interval 1.07 to 2.93	0.03 units on a scale Interval -0.61 to 0.66	0.52 units on a scale Interval 0.05 to 0.99
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC3/Day1 (n= 45, 47, 39)	0.64 units on a scale Interval 0.07 to 1.21	-0.21 units on a scale Interval -0.81 to 0.4	0.03 units on a scale Interval -0.41 to 0.46
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC3/Day8 (n= 38, 35, 32)	1.54 units on a scale Interval 0.57 to 2.5	0.28 units on a scale Interval -0.46 to 1.03	0.41 units on a scale Interval 0.0 to 0.82
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC4/Day1 (n= 43, 43, 38)	0.72 units on a scale Interval -0.18 to 1.62	0.11 units on a scale Interval -0.5 to 0.73	0.28 units on a scale Interval -0.16 to 0.71
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC4/Day8 (n= 33, 33, 27)	1.39 units on a scale Interval 0.2 to 2.58	1.08 units on a scale Interval 0.23 to 1.92	1.20 units on a scale Interval 0.48 to 1.93
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC5/Day1 (n= 35, 34, 29)	0.14 units on a scale Interval -0.67 to 0.95	-0.05 units on a scale Interval -0.88 to 0.78	0.49 units on a scale Interval -0.1 to 1.09
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC5/Day8 (n= 29, 26, 25)	0.78 units on a scale Interval -0.42 to 1.97	0.88 units on a scale Interval -0.19 to 1.94	0.76 units on a scale Interval -0.03 to 1.55
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC6/Day1 (n= 27, 28, 28)	0.18 units on a scale Interval -0.76 to 1.12	0.17 units on a scale Interval -0.68 to 1.01	0.66 units on a scale Interval -0.04 to 1.36
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleC6/Day8 (n= 25, 25, 21)	1.00 units on a scale Interval -0.16 to 2.16	1.04 units on a scale Interval 0.17 to 1.91	1.20 units on a scale Interval 0.32 to 2.08
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA1/Day1 (n= 35, 33, 21)	0.49 units on a scale Interval -0.2 to 1.18	0.39 units on a scale Interval -0.34 to 1.13	0.96 units on a scale Interval 0.28 to 1.64
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA2/Day1 (n= 32, 30, 14)	0.25 units on a scale Interval -0.52 to 1.02	0.16 units on a scale Interval -0.67 to 0.98	0.10 units on a scale Interval -0.82 to 1.01
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA3/Day1 (n= 27, 26, 10)	0.02 units on a scale Interval -0.82 to 0.87	-0.20 units on a scale Interval -1.15 to 0.76	0.27 units on a scale Interval -0.43 to 0.96
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA4/Day1 (n= 22, 25, 0)	0.33 units on a scale Interval -0.43 to 1.1	0.23 units on a scale Interval -0.58 to 1.05	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA5/Day1 (n= 17, 23, 12)	0.36 units on a scale Interval -0.54 to 1.27	0.12 units on a scale Interval -1.02 to 1.27	0.40 units on a scale Interval -0.56 to 1.37
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA6/Day1 (n= 17, 16, 10)	0.16 units on a scale Interval -0.47 to 0.79	0.28 units on a scale Interval -0.82 to 1.39	0.12 units on a scale Interval -0.92 to 1.15
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA7/Day1 (n= 15, 15, 0)	0.12 units on a scale Interval -0.68 to 0.92	0.00 units on a scale Interval -1.14 to 1.15	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA8/Day1 (n= 15, 14, 10)	-0.07 units on a scale Interval -0.96 to 0.82	0.30 units on a scale Interval -0.7 to 1.29	0.42 units on a scale Interval -0.39 to 1.23
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA9/Day1 (n= 13, 11, 0)	-0.13 units on a scale Interval -1.03 to 0.77	1.05 units on a scale Interval 0.09 to 2.0	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at CycleA10/Day1 (n= 0, 10, 0)	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.	1.03 units on a scale Interval 0.06 to 2.01	NA units on a scale Data was not summarized because there was insufficient number of participants to calculate change from baseline at visit.
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score Change at EOT (n= 40, 35, 31)	0.69 units on a scale Interval -0.26 to 1.64	0.69 units on a scale Interval -0.22 to 1.59	0.91 units on a scale Interval 0.06 to 1.77

Adverse Events

Axitinib + Pemetrexed/Cisplatin (Phase 1)

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2)

Serious events: 19 serious events

Other events: 54 other events

Deaths: 0 deaths

Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2)

Serious events: 20 serious events

Other events: 56 other events

Deaths: 0 deaths

Pemetrexed/Cisplatin (Phase 2)

Serious events: 13 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Serious adverse events
Measure	Axitinib + Pemetrexed/Cisplatin (Phase 1) n=10 participants at risk Lead-in axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily (BID) from Day -5, -4 or -3 till Day 18 of Cycle 1 then continuously from Day 3 of Cycle 2 along with pemetrexed 500 milligram per square meter (mg/m\^2) infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable adverse events (AEs), or participant withdrawal.	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 participants at risk Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=58 participants at risk Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=55 participants at risk Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Infections and infestations Pneumonia	0.00% 0/10 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.	3.6% 2/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Anaemia	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	3.4% 2/58 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.	1.8% 1/55 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 Febrile neutropenia	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Pancytopenia	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 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.	1.8% 1/55 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	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 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.	1.8% 1/55 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.
Cardiac disorders Angina unstable	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.
Cardiac disorders Atrial fibrillation	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 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.	1.8% 1/55 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.
Cardiac disorders Bradycardia	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.
Cardiac disorders Pericarditis	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.
Cardiac disorders Left ventricular dysfunction	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 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.	1.8% 1/55 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 Colitis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Gastritis	0.00% 0/10 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.	1.8% 1/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 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.	7.3% 4/55 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.	1.7% 1/58 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.	1.8% 1/55 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 Oesophagitis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Small intestine ulcer	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 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.	9.1% 5/55 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.	3.4% 2/58 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.	3.6% 2/55 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 toxicity	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Chest pain	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 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.	3.6% 2/55 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	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Sudden death	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 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.	1.8% 1/55 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.
Hepatobiliary disorders Cholangitis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 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.	1.8% 1/55 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.
Hepatobiliary disorders Cholecystitis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 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.	1.8% 1/55 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.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Lower respiratory tract infection	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 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.	1.8% 1/55 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 Oesophageal candidiasis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Postoperative wound infection	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Sepsis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Device related infection	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 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.	1.8% 1/55 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.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Dehydration	0.00% 0/10 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.	5.5% 3/55 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.	5.2% 3/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 chest pain	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Depressed level of consciousness	0.00% 0/10 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.	1.8% 1/55 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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
Measure	Axitinib + Pemetrexed/Cisplatin (Phase 1) n=10 participants at risk Lead-in axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily (BID) from Day -5, -4 or -3 till Day 18 of Cycle 1 then continuously from Day 3 of Cycle 2 along with pemetrexed 500 milligram per square meter (mg/m\^2) infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable adverse events (AEs), or participant withdrawal.	Axitinib (Continuous) + Pemetrexed/Cisplatin (Phase 2) n=55 participants at risk Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Axitinib (Modified) + Pemetrexed/Cisplatin (Phase 2) n=58 participants at risk Axitinib (AG-013736) tablet at a starting dose of 5 mg orally BID from Day 2-19 in cycles of chemotherapy phase, except the last cycle, where axitinib (AG-013736) was administered on Day 2-21 along with pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase and axitinib (AG-013736) tablet 5 mg orally BID in single-agent maintenance phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.	Pemetrexed/Cisplatin (Phase 2) n=55 participants at risk Pemetrexed 500 mg/m\^2 infusion and cisplatin 75 mg/m\^2 infusion over a 2 hour period on Day 1 of each cycle up to 6 cycles of length 21 days each in chemotherapy phase. Treatment was continued until progression of disease, unmanageable AEs, or participant withdrawal.
Eye disorders Vision blurred	0.00% 0/10 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.	3.6% 2/55 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.	3.4% 2/58 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.	5.5% 3/55 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	10.0% 1/10 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.	1.8% 1/55 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.	5.2% 3/58 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.	3.6% 2/55 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 Anaemia	50.0% 5/10 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.	12.7% 7/55 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.	32.8% 19/58 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.	41.8% 23/55 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 Leukopenia	10.0% 1/10 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.	10.9% 6/55 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.	13.8% 8/58 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.	5.5% 3/55 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	50.0% 5/10 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.	30.9% 17/55 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.	20.7% 12/58 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.	27.3% 15/55 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	20.0% 2/10 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.	14.5% 8/55 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.	6.9% 4/58 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.	5.5% 3/55 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 Hypoacusis	0.00% 0/10 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.	5.5% 3/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	0.00% 0/10 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.	5.5% 3/55 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.	5.2% 3/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	10.0% 1/10 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.	16.4% 9/55 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.	6.9% 4/58 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.	9.1% 5/55 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	10.0% 1/10 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.	9.1% 5/55 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.	13.8% 8/58 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.	12.7% 7/55 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	0.00% 0/10 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.	7.3% 4/55 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.	1.7% 1/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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	40.0% 4/10 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.	36.4% 20/55 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.	25.9% 15/58 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.	41.8% 23/55 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	50.0% 5/10 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.	40.0% 22/55 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.	34.5% 20/58 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.	16.4% 9/55 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 Flatulence	0.00% 0/10 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.	7.3% 4/55 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.	1.7% 1/58 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.	1.8% 1/55 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 Haemorrhoids	0.00% 0/10 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.	5.5% 3/55 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.	3.4% 2/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Mouth ulceration	0.00% 0/10 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.	7.3% 4/55 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.	5.2% 3/58 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.	5.5% 3/55 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	60.0% 6/10 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.	67.3% 37/55 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.	51.7% 30/58 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.	58.2% 32/55 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	0.00% 0/10 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.	18.2% 10/55 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.	12.1% 7/58 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.	5.5% 3/55 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	40.0% 4/10 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.	47.3% 26/55 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.	32.8% 19/58 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.	25.5% 14/55 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	50.0% 5/10 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.	16.4% 9/55 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.	19.0% 11/58 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.	12.7% 7/55 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 Chest pain	10.0% 1/10 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.	10.9% 6/55 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.	10.3% 6/58 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.	9.1% 5/55 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	80.0% 8/10 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.	49.1% 27/55 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.	43.1% 25/58 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.	45.5% 25/55 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	0.00% 0/10 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.	7.3% 4/55 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.	3.4% 2/58 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.	7.3% 4/55 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 peripheral	0.00% 0/10 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.	5.5% 3/55 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.	10.3% 6/58 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.	5.5% 3/55 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 Pain	0.00% 0/10 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.	5.5% 3/55 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.	10.3% 6/58 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.	3.6% 2/55 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	0.00% 0/10 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.	9.1% 5/55 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.	17.2% 10/58 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.	5.5% 3/55 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 Nasopharyngitis	0.00% 0/10 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.	16.4% 9/55 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.	3.4% 2/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Urinary tract infection	0.00% 0/10 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.	5.5% 3/55 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.	5.2% 3/58 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.	1.8% 1/55 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	20.0% 2/10 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.	9.1% 5/55 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.	3.4% 2/58 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.	5.5% 3/55 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 thyroid stimulating hormone increased	0.00% 0/10 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.	7.3% 4/55 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.	3.4% 2/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Creatinine renal clearance decreased	0.00% 0/10 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.	7.3% 4/55 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.	5.2% 3/58 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.	5.5% 3/55 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	0.00% 0/10 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.	9.1% 5/55 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.	3.4% 2/58 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.	1.8% 1/55 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	10.0% 1/10 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.	7.3% 4/55 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.	10.3% 6/58 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.	7.3% 4/55 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	70.0% 7/10 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.	52.7% 29/55 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.	48.3% 28/58 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.	41.8% 23/55 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	10.0% 1/10 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.	9.1% 5/55 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.	12.1% 7/58 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.	9.1% 5/55 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 Pain in extremity	10.0% 1/10 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.	7.3% 4/55 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.	6.9% 4/58 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/55 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 Dizziness	0.00% 0/10 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.	7.3% 4/55 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.	10.3% 6/58 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.	5.5% 3/55 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	20.0% 2/10 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.	16.4% 9/55 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.	10.3% 6/58 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.	1.8% 1/55 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	20.0% 2/10 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.	21.8% 12/55 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.	29.3% 17/58 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.	16.4% 9/55 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	10.0% 1/10 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.	9.1% 5/55 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.	3.4% 2/58 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.	1.8% 1/55 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.