Trial Outcomes & Findings for A Phase III Trial For Patients With Metastatic Breast Cancer (NCT NCT00191152)

NCT ID: NCT00191152

Last Updated: 2009-12-24

Results Overview

Time to disease progression (TTDP) at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. TTDP censored at earliest of: 1) date of death not due to disease; or 2) date of last contact for participants alive without disease progression; or 3) start date of other anti-tumor therapy; or 4) first dose date of crossover treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

475 participants

Primary outcome timeframe

Randomization date to the earliest date of first documented disease progression date or the date of death if the participant died due to study disease (up to 82 months)

Results posted on

2009-12-24

Participant Flow

Not all participants who completed initial treatment went on to crossover treatment. Per protocol, participants had the option to go off study without receiving crossover treatment.

Participant milestones

Participant milestones
Measure	Gemcitabine Plus Docetaxel Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2),intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO) twice a day (BID), Days 1-14, every 21 days until PD at which time all treatment is discontinued. PD during crossover was defined as the Response Evaluation Criteria in Solid Tumors (RECIST) guideline with the tumor measurement at the start of crossover treatment (or end of initial treatment) considered as the crossover baseline, with subsequent tumor measurements during crossover treatment compared to the crossover baseline.	Docetaxel Plus Capecitabine Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID), Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.
Initial Treatment STARTED	239	236
Initial Treatment Received Initial Treatment	236	227
Initial Treatment COMPLETED	98	83
Initial Treatment NOT COMPLETED	141	153
Crossover Treatment STARTED	77	81
Crossover Treatment Received Treatment	76	80
Crossover Treatment COMPLETED	50	53
Crossover Treatment NOT COMPLETED	27	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Gemcitabine Plus Docetaxel Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2),intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO) twice a day (BID), Days 1-14, every 21 days until PD at which time all treatment is discontinued. PD during crossover was defined as the Response Evaluation Criteria in Solid Tumors (RECIST) guideline with the tumor measurement at the start of crossover treatment (or end of initial treatment) considered as the crossover baseline, with subsequent tumor measurements during crossover treatment compared to the crossover baseline.	Docetaxel Plus Capecitabine Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID), Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.
Initial Treatment Adverse Event	43	67
Initial Treatment Physician Decision	40	31
Initial Treatment Withdrawal by Subject	40	28
Initial Treatment Lost to Follow-up	0	6
Initial Treatment Other	18	21
Crossover Treatment Adverse Event	8	8
Crossover Treatment Physician Decision	7	7
Crossover Treatment Withdrawal by Subject	6	9
Crossover Treatment Lost to Follow-up	2	1
Crossover Treatment Other	4	3

Baseline Characteristics

A Phase III Trial For Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine Plus Docetaxel n=239 Participants Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2), intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO)twice a day (BID), Days 1-14, every 21 days until progressive disease (PD) at which time all treatment is discontinued.	Docetaxel Plus Capecitabine n=236 Participants Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID),Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.	Total n=475 Participants Total of all reporting groups
Age Continuous	55.8 years STANDARD_DEVIATION 11.77 • n=5 Participants	54.6 years STANDARD_DEVIATION 11.60 • n=7 Participants	55.2 years STANDARD_DEVIATION 11.69 • n=5 Participants
Sex: Female, Male Female	237 Participants n=5 Participants	1 Participants n=7 Participants	238 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	235 Participants n=7 Participants	237 Participants n=5 Participants
Region of Enrollment United States	173 participants n=5 Participants	166 participants n=7 Participants	339 participants n=5 Participants
Region of Enrollment Taiwan	15 participants n=5 Participants	18 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment Mexico	14 participants n=5 Participants	15 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Puerto Rico	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Argentina	11 participants n=5 Participants	13 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment Brazil	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Australia	11 participants n=5 Participants	12 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Korea, Republic of	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Karnofsky Performance Status-Baseline <=60 Needs increasing assistance up to Death (0)	0 units on a scale n=5 Participants	0 units on a scale n=7 Participants	0 units on a scale n=5 Participants
Karnofsky Performance Status-Baseline 70 - Unable to carry on normal activity	16 units on a scale n=5 Participants	15 units on a scale n=7 Participants	31 units on a scale n=5 Participants
Karnofsky Performance Status-Baseline 80 - Activity with effort; some signs of disease	44 units on a scale n=5 Participants	40 units on a scale n=7 Participants	84 units on a scale n=5 Participants
Karnofsky Performance Status-Baseline 90 - Normal activity; minor signs of disease	101 units on a scale n=5 Participants	101 units on a scale n=7 Participants	202 units on a scale n=5 Participants
Karnofsky Performance Status-Baseline 100 - Normal no complaints; no evidence of disease	74 units on a scale n=5 Participants	75 units on a scale n=7 Participants	149 units on a scale n=5 Participants
Karnofsky Performance Status-Baseline Missing	4 units on a scale n=5 Participants	5 units on a scale n=7 Participants	9 units on a scale n=5 Participants
Race/Ethnicity Caucasian	160 participants n=5 Participants	158 participants n=7 Participants	318 participants n=5 Participants
Race/Ethnicity African Descent	23 participants n=5 Participants	12 participants n=7 Participants	35 participants n=5 Participants
Race/Ethnicity Oriental	28 participants n=5 Participants	30 participants n=7 Participants	58 participants n=5 Participants
Race/Ethnicity Hispanic	26 participants n=5 Participants	36 participants n=7 Participants	62 participants n=5 Participants
Race/Ethnicity Other	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization date to the earliest date of first documented disease progression date or the date of death if the participant died due to study disease (up to 82 months)

Population: Intent-to-treat (ITT) population: all randomized participants. Censored participants in initial treatment: 68 gemcitabine/docetaxel arm; 83 docetaxel/capecitabine arm.

Outcome measures

Outcome measures
Measure	Capecitabine n=239 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=236 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Time to Disease Progression (Initial Treatment)	9.28 months Interval 7.73 to 10.79	8.88 months Interval 7.37 to 11.05

SECONDARY outcome

Timeframe: Date of first dose of crossover treatment to date of first-documented disease progression after receiving first crossover treatment or date of death due to study disease, whichever came first (up to 82 months)

Population: ITT population: all randomized participants. Censored participants in crossover treatment: 13 in capecitabine arm; 10 in gemcitabine arm.

For crossover treatment, time to disease progression (TTDP) was defined as the number of months between the first dose date of crossover treatment and the date of disease progression or the date of death due to disease under study, whichever came first. TTDP for crossover treatment only applied to those participants who crossed over from initial treatment to crossover treatment. TTDP censored at earliest of: 1)date of death not due to disease; or 2)date of last contact for participants alive without disease progression; or 3)start date of other anti-tumor therapy due to progression.

Outcome measures

Outcome measures
Measure	Capecitabine n=77 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=81 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Time to Disease Progression (Crossover Treatment)	4.51 months Interval 2.11 to 7.8	2.34 months Interval 2.04 to 3.78

SECONDARY outcome

Timeframe: Date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 82 months)

Population: ITT: all randomized participants. Censored participants (initial treatment): 64 in gemcitabine/docetaxel arm; 80 in docetaxel/capecitabine arm.

For initial treatment, progression-free survival (PFS) was defined as the number of months between the date of randomization and the date of first documented disease progression or the date of death due to any cause, whichever came first. Time to PFS was censored at the earliest of: 1) date of last contact for participants alive without disease progression; or 2) start date of other anti-tumor therapy for progression; or 3) first dose date of crossover treatment.

Outcome measures

Outcome measures
Measure	Capecitabine n=239 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=236 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Progression-Free Survival (Initial Treatment)	9.01 months Interval 7.73 to 10.53	8.88 months Interval 7.27 to 10.89

SECONDARY outcome

Timeframe: First dose date of crossover treatment to date of first-documented progression after receiving crossover treatment or date of death due to any cause, whichever came first (up to 82 months)

Population: ITT population: all randomized participants. Censored participants, crossover treatment: 13 in capecitabine arm; 10 in gemcitabine arm.

For crossover treatment, progression-free survival (PFS) was defined as the number of months between first dose date of crossover treatment and date of documented disease progression or date of death due to any cause, whichever came first. PFS for crossover treatment only applied to those participants who crossed over from initial treatment to crossover treatment. PFS was censored at the earliest of: 1) date of last contact for participants alive without disease progression; or 2) start date of other anti-tumor therapy for participants with documented disease progression.

Outcome measures

Outcome measures
Measure	Capecitabine n=77 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=81 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Progression-Free Survival (Crossover Treatment)	4.51 months Interval 2.11 to 7.8	2.34 months Interval 2.04 to 3.78

SECONDARY outcome

Timeframe: Date of response (CR or PR) until the first date of documented progression or death from any cause (up to 82 months)

Population: ITT population: participants with CR or PR as best overall response (initial treatment). Censored participants: 16 in gemcitabine/docetaxel arm; 30 in docetaxel/capecitabine arm.

Among tumor responders, duration of tumor response was measured from the date of response (complete response \[CR\] or partial response \[PR\] until the first date of documented progression or death from any cause. Duration of response was censored at the earliest of: 1) date of last contact for participants alive without disease progression (DP); or 2) start date of other anti-tumor therapy for DP; or 3) dose date of crossover treatment.

Outcome measures

Outcome measures
Measure	Capecitabine n=77 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=85 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Duration of Response (Initial Treatment)	9.11 months Interval 7.6 to 11.94	10.39 months Interval 8.22 to 13.75

SECONDARY outcome

Timeframe: Date of CR or PR until first date of recurrent or progressive disease after receiving crossover treatment was objectively documented or date of date due to any cause, whichever came first (up to 82 months)

Population: ITT population: participants with CR or PR as best overall response at crossover treatment. Censored participants: 4 in capecitabine arm; 2 in gemcitabine arm.

At crossover treatment, duration of response was measured from the time criteria were met for complete response (CR) or partial response (PR), until first date that recurrent or progressive disease was objectively documented or date of death due to any cause, whichever came first. This definition only applied to those who crossed over \& achieved CR or PR in crossover treatment. Duration of response censored at earliest of: 1) date of last contact for those alive without disease progression; or 2) start date of other anti-tumor therapy for documented disease progression.

Outcome measures

Outcome measures
Measure	Capecitabine n=11 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=7 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Duration of Response (Crossover Treatment)	25.89 months Interval 4.64 to 45.03	42.50 months Interval 16.02 to 48.22

SECONDARY outcome

Timeframe: Date of randomization to date of death from any cause (up to 82 months)

Population: Intent to treat population: all randomized participant. Censored participants: 75 in gemcitabine/docetaxel arm; 72 in docetaxel/capecitabine arm.

Overall survival time was defined as the number of months between the date of randomization and the date of death due to any cause. The overall survival time was censored at the date of last contact for participants who were still alive.

Outcome measures

Outcome measures
Measure	Capecitabine n=239 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=236 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Overall Survival	22.99 months Interval 18.82 to 25.69	23.29 months Interval 18.55 to 25.53

SECONDARY outcome

Timeframe: Best response from start of treatment until disease progression/recurrence (up to 82 months)

Population: ITT population.

Best overall response was the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that did not meet above criteria.

Outcome measures

Outcome measures
Measure	Capecitabine n=239 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=236 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Best Overall Response (Initial Treatment) Stable Disease	96 participants	90 participants
Best Overall Response (Initial Treatment) Progressive Disease	32 participants	27 participants
Best Overall Response (Initial Treatment) Unknown	34 participants	34 participants
Best Overall Response (Initial Treatment) Complete Response (confirmed)	6 participants	6 participants
Best Overall Response (Initial Treatment) Partial Response (confirmed)	71 participants	79 participants

SECONDARY outcome

Timeframe: Best response from start of treatment until disease progression/recurrence (up to 82 months)

Population: Only included participants who crossed over from initial treatment to crossover treatment.

Best overall response was the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response assessed using RECIST criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that did not meet above criteria.

Outcome measures

Outcome measures
Measure	Capecitabine n=77 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=81 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Best Overall Response (Crossover Treatment) Complete Response (confirmed)	1 participants	1 participants
Best Overall Response (Crossover Treatment) Partial Response (confirmed)	10 participants	6 participants
Best Overall Response (Crossover Treatment) Stable Disease	19 participants	20 participants
Best Overall Response (Crossover Treatment) Progressive Disease	34 participants	36 participants
Best Overall Response (Crossover Treatment) Unknown	13 participants	18 participants

SECONDARY outcome

Timeframe: Baseline until crossover treatment began (up to 82 months)

Population: Intent-to-treat population, initial treatment, participants with KPS at baseline and end of initial treatment.

KPS ranges from 0 to 100, subdivided into three categories: incapacitated (0-40), self-care (50-70), and normal activity (80-100).

Outcome measures

Outcome measures
Measure	Capecitabine n=212 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=214 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Initial Treatment) Baseline	90.85 units on a scale Standard Deviation 8.159	90.09 units on a scale Standard Deviation 8.335
Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Initial Treatment) Change from Baseline	-3.30 units on a scale Standard Deviation 9.259	-3.27 units on a scale Standard Deviation 9.118

SECONDARY outcome

Timeframe: First day of crossover treatment until end of crossover treatment at trial discontinuation (up to 82 moths)

Population: Participants with KPS at baseline (conclusion of initial treatment) and end of crossover treatment

KPS ranges from 0 to 100, subdivided into three categories: incapacitated (0-40), self-care (50-70), and normal activity (80-100).

Outcome measures

Outcome measures
Measure	Capecitabine n=66 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=63 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Crossover Treatment) Baseline	89.09 units on a scale Standard Deviation 7.174	87.94 units on a scale Standard Deviation 9.360
Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Crossover Treatment) Change from Baseline	-0.30 units on a scale Standard Deviation 7.839	-1.27 units on a scale Standard Deviation 9.068

SECONDARY outcome

Timeframe: Baseline until crossover treatment began (up to 82 months)

Population: Participants with RSCL at baseline and end of initial treatment.

RSCL includes 4 scales to assess quality of life (QOL) endpoints: 1) a 23-item physical distress level with scale score ranges from 23 to 92 \[low score represents better QOL\] 2)a 7-item psychological distress level with scale score ranges from 7 to 28\[low score represents better QOL\] 3)8-item activity level with scale score ranges from 8 to 32 \[high score represents better QOL\]; 1-item overall valuation of life with score range from 1 to 7 \[low score represents better QOL\].

Outcome measures

Outcome measures
Measure	Capecitabine n=117 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=118 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Summary of Changes in Rotterdam Symptom Checklist (RSCL) by Treatment (Initial Treatment) Baseline	68.09 units on a scale Standard Deviation 25.103	72.32 units on a scale Standard Deviation 23.693
Summary of Changes in Rotterdam Symptom Checklist (RSCL) by Treatment (Initial Treatment) Change from Baseline	2.42 units on a scale Standard Deviation 27.093	-2.68 units on a scale Standard Deviation 26.685

SECONDARY outcome

Timeframe: First day of crossover treatment until end of crossover treatment at trial discontinuation (up to 82 months)

Population: Participants with RSCL at baseline (conclusion of initial treatment)and end of crossover treatment

Outcome measures

Outcome measures
Measure	Capecitabine n=30 Participants capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.	Gemcitabine n=24 Participants gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Summary of Changes in Rotterdam Symptom Checklist by Treatment (Crossover Treatment) Baseline	75.00 units on a scale Standard Deviation 20.876	76.39 units on a scale Standard Deviation 17.663
Summary of Changes in Rotterdam Symptom Checklist by Treatment (Crossover Treatment) Change from Baseline	-2.78 units on a scale Standard Deviation 21.029	-0.69 units on a scale Standard Deviation 27.133

Adverse Events

Gemcitabine Plus Docetaxel

Serious events: 72 serious events

Other events: 233 other events

Deaths: 0 deaths

Docetaxel Plus Capecitabine

Serious events: 55 serious events

Other events: 221 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 1-800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Gemcitabine Plus Docetaxel n=237 participants at risk Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2), intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO) twice a day (BID), Days 1-14, every 21 days until PD at which time all treatment is discontinued.	Docetaxel Plus Capecitabine n=226 participants at risk Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID), Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.
Blood and lymphatic system disorders Anaemia	0.84% 2/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Febrile neutropenia	3.8% 9/237 • Number of events 10 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	4.0% 9/226 • Number of events 9 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Leukocytosis	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Leukopenia	2.5% 6/237 • Number of events 9 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.88% 2/226 • Number of events 3 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Lymphopenia	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Neutropenia	10.5% 25/237 • Number of events 38 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	3.1% 7/226 • Number of events 11 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Thrombocytopenia	0.84% 2/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Cardiac disorders Atrial fibrillation	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Cardiac disorders Cardiac failure congestive	0.84% 2/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Cardiac disorders Cardiac tamponade	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Cardiac disorders Cardiopulmonary failure	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Cardiac disorders Pericardial effusion	1.7% 4/237 • Number of events 4 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Cardiac disorders Tachycardia	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Abdominal pain	0.84% 2/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Diarrhoea	0.84% 2/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	1.8% 4/226 • Number of events 4 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Diverticulitis	0.42% 1/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Enterocolitis	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Intestinal perforation	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Nausea	0.84% 2/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.88% 2/226 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Oesophagitis	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Pancreatitis	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Ruptured diverticulum	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Volvulus of bowel	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Vomiting	1.7% 4/237 • Number of events 4 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	1.3% 3/226 • Number of events 3 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Asthenia	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Catheter site erythema	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Chest pain	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Fatigue	1.3% 3/237 • Number of events 3 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.88% 2/226 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Lethargy	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Malaise	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Mucosal inflammation	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Multi-organ failure	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Oedema peripheral	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Pyrexia	1.7% 4/237 • Number of events 4 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	2.2% 5/226 • Number of events 5 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Infections and infestations Bronchopneumonia	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Infections and infestations Catheter related infection	0.00% 0/237 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.44% 1/226 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Infections and infestations Catheter sepsis	0.42% 1/237 • Number of events 1 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Infections and infestations Catheter site infection	0.84% 2/237 • Number of events 2 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	0.00% 0/226 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.

Other adverse events
Measure	Gemcitabine Plus Docetaxel n=237 participants at risk Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2), intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO) twice a day (BID), Days 1-14, every 21 days until PD at which time all treatment is discontinued.	Docetaxel Plus Capecitabine n=226 participants at risk Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID), Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins. Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.
Blood and lymphatic system disorders Anaemia	47.7% 113/237 • Number of events 278 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	26.1% 59/226 • Number of events 110 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Leukopenia	36.3% 86/237 • Number of events 294 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	11.1% 25/226 • Number of events 53 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Neutropenia	81.4% 193/237 • Number of events 883 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	32.3% 73/226 • Number of events 216 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Blood and lymphatic system disorders Thrombocytopenia	29.5% 70/237 • Number of events 152 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	2.7% 6/226 • Number of events 13 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Eye disorders Lacrimation increased	6.3% 15/237 • Number of events 23 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	12.8% 29/226 • Number of events 38 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Abdominal pain	13.9% 33/237 • Number of events 42 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	13.3% 30/226 • Number of events 43 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Constipation	27.4% 65/237 • Number of events 100 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	21.7% 49/226 • Number of events 71 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Diarrhoea	46.8% 111/237 • Number of events 217 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	47.8% 108/226 • Number of events 221 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Dyspepsia	8.9% 21/237 • Number of events 28 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	12.4% 28/226 • Number of events 44 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Nausea	47.7% 113/237 • Number of events 233 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	52.2% 118/226 • Number of events 248 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Stomatitis	19.8% 47/237 • Number of events 92 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	26.5% 60/226 • Number of events 113 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Gastrointestinal disorders Vomiting	30.0% 71/237 • Number of events 120 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	32.7% 74/226 • Number of events 134 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Asthenia	19.0% 45/237 • Number of events 104 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	14.2% 32/226 • Number of events 61 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Chest pain	6.3% 15/237 • Number of events 23 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	5.3% 12/226 • Number of events 13 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Fatigue	54.4% 129/237 • Number of events 285 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	53.1% 120/226 • Number of events 224 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Mucosal inflammation	16.0% 38/237 • Number of events 81 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	28.8% 65/226 • Number of events 117 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Oedema	13.1% 31/237 • Number of events 77 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	11.9% 27/226 • Number of events 46 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Oedema peripheral	22.8% 54/237 • Number of events 90 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	19.5% 44/226 • Number of events 67 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Pain	10.5% 25/237 • Number of events 45 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	8.0% 18/226 • Number of events 31 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Pyrexia	25.3% 60/237 • Number of events 93 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	14.6% 33/226 • Number of events 38 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
General disorders Rigors	6.3% 15/237 • Number of events 22 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	4.0% 9/226 • Number of events 9 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Infections and infestations Candidiasis	2.1% 5/237 • Number of events 9 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	5.3% 12/226 • Number of events 14 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Infections and infestations Upper respiratory tract infection	7.2% 17/237 • Number of events 21 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	3.5% 8/226 • Number of events 8 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Infections and infestations Urinary tract infection	5.5% 13/237 • Number of events 19 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	4.9% 11/226 • Number of events 11 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Investigations Alanine aminotransferase increased	11.8% 28/237 • Number of events 42 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	5.8% 13/226 • Number of events 19 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Investigations Aspartate aminotransferase increased	8.9% 21/237 • Number of events 31 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	6.2% 14/226 • Number of events 22 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Investigations Weight decreased	6.8% 16/237 • Number of events 23 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	4.4% 10/226 • Number of events 14 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Metabolism and nutrition disorders Anorexia	24.9% 59/237 • Number of events 122 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	26.1% 59/226 • Number of events 92 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Metabolism and nutrition disorders Dehydration	8.9% 21/237 • Number of events 24 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	9.7% 22/226 • Number of events 26 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Metabolism and nutrition disorders Hyperglycaemia	8.9% 21/237 • Number of events 47 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	6.6% 15/226 • Number of events 21 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Metabolism and nutrition disorders Hypocalcaemia	4.2% 10/237 • Number of events 22 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	5.3% 12/226 • Number of events 17 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Metabolism and nutrition disorders Hypokalaemia	5.5% 13/237 • Number of events 16 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	6.2% 14/226 • Number of events 17 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Musculoskeletal and connective tissue disorders Arthralgia	18.1% 43/237 • Number of events 60 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	17.3% 39/226 • Number of events 62 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Musculoskeletal and connective tissue disorders Back pain	10.1% 24/237 • Number of events 34 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	10.2% 23/226 • Number of events 31 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Musculoskeletal and connective tissue disorders Bone pain	8.9% 21/237 • Number of events 29 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	4.4% 10/226 • Number of events 12 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Musculoskeletal and connective tissue disorders Myalgia	19.4% 46/237 • Number of events 105 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	14.6% 33/226 • Number of events 62 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Musculoskeletal and connective tissue disorders Pain in extremity	10.5% 25/237 • Number of events 42 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	11.1% 25/226 • Number of events 31 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Nervous system disorders Dizziness	8.9% 21/237 • Number of events 24 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	8.4% 19/226 • Number of events 32 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Nervous system disorders Dysgeusia	13.5% 32/237 • Number of events 50 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	12.8% 29/226 • Number of events 39 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
Nervous system disorders Headache	17.3% 41/237 • Number of events 53 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.	14.2% 32/226 • Number of events 38 A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.