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Trial record 33 of 157 for:    Diseases | ( Map: Costa Rica )

ToGA Study - A Study of Herceptin (Trastuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With HER2-Positive Advanced Gastric Cancer

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ClinicalTrials.gov Identifier: NCT01041404
Recruitment Status : Completed
First Posted : December 31, 2009
Results First Posted : November 5, 2014
Last Update Posted : November 5, 2014
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastric Cancer
Interventions Drug: Trastuzumab
Drug: Fluorouracil
Drug: Cisplatin
Drug: Capecitabine
Enrollment 584
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description Participants received fluoropyrimidine (EITHER 5-fluorouracil [5-FU] or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 milligrams per square meter (mg/m^2), intravenously (IV), on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, orally (PO), twice daily (BID) from the evening of Day 1 through the morning of Day 15. Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 milligrams per kilogram (mg/kg), IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Period Title: Overall Study
Started 290 294
Entered Follow-Up 251 251
Died in Follow-up 199 200
Lost to Follow-up 12 10
Alive in Follow-up 40 41
Completed 0 [1] 0 [1]
Not Completed 290 294
Reason Not Completed
Adverse Event             45             35
Lack of Efficacy             200             210
Violation of Selection Criteria             0             1
Protocol Violation             4             0
Withdrawal by Subject             29             23
Failure to Return             1             2
Not Specified             11             23
[1]
Summary of withdrawals represents withdrawals from treatment, rather than withdrawals from study.
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H) Total
Hide Arm/Group Description Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15. Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15. Total of all reporting groups
Overall Number of Baseline Participants 290 294 584
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomized participants who received at least 1 dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 290 participants 294 participants 584 participants
58.5  (11.22) 59.4  (10.75) 59.0  (10.99)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 294 participants 584 participants
Female
72
  24.8%
68
  23.1%
140
  24.0%
Male
218
  75.2%
226
  76.9%
444
  76.0%
1.Primary Outcome
Title Overall Survival (OS) - Percentage of Participants With an Event
Hide Description OS was defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
Time Frame Baseline (BL), Days 1, 8, 15, 22, 43, 64, 85, 106, 127, and every 21 days until the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Measure Type: Number
Unit of Measure: percentage of participants
62.8 56.8
2.Primary Outcome
Title Overall Survival - Time to Event
Hide Description The median time, in months, from the date of randomization to the date of an OS event. Participants were censored at the last date tumor measurement, the last date in the study drug log, or the date of last follow-up.
Time Frame BL, Days 1, 8, 15, 22, 43, 64, 85, 106, 127, and every 21 days until the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Median (95% Confidence Interval)
Unit of Measure: months
11.1
(10 to 13)
13.8
(12 to 16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluoropyrimidine/Cisplatin (FP), Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.60 to 0.91
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Progression-Free Survival (PFS) - Percentage of Participants With an Event
Hide Description PFS was defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Measure Type: Number
Unit of Measure: percentage of participants
81.0 76.9
4.Secondary Outcome
Title Progression-Free Survival - Time to Event
Hide Description The median time, in months, from the date of randomization to the date of a PFS event. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine, Cisplatin Trastuzumab, Fluoropyrimidine, Cisplatin
Hide Arm/Group Description:
Participants received fluorouracil 800 mg/m^2 IV on Days 1 through 5 of cycle every 3 weeks for 6 cycles. Participants also received cisplatin 80 mg/m^2, IV, on Day 1 of cycle every 3 weeks for 6 cycles; as well as, capecitabine 1000 mg/m^2, PO, twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
Participants received an initial loading dose of trastuzumab 8 mg/kg, IV, on Day 1 of cycle, followed by 6 mg/kg, IV, every 3 weeks until disease progression. Participants also received fluorouracil 800 mg/m^2 IV on Days 1 through 5 of cycle every 3 weeks for 6 cycles; cisplatin 80 mg/m^2 IV on Day 1 of cycle every 3 weeks for 6 cycles; and capecitabine 1000 mg/m^2 PO twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
Overall Number of Participants Analyzed 290 294
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(5 to 6)
6.7
(6 to 8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluoropyrimidine, Cisplatin, Trastuzumab, Fluoropyrimidine, Cisplatin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.59 to 0.85
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Progression (TTP) - Percentage of Participants With an Event
Hide Description TTP was defined as the time from the date of randomization and the date of the first occurrence of PD. Participants were censored at the last date of tumor assessment, the last date in the study drug log, or the last date of follow-up.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Measure Type: Number
Unit of Measure: percentage of participants
74.1 70.7
6.Secondary Outcome
Title Time to Progression - Time to Event
Hide Description The median time, in months, from the date of randomized to the date of a TTP event. Participants were censored at the last date of tumor assessment, the last date in the study drug log, or the last date of follow-up.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Median (95% Confidence Interval)
Unit of Measure: months
5.6
(5 to 6)
7.1
(6 to 8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluoropyrimidine/Cisplatin (FP), Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.58 to 0.85
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description For TLs, a CR was defined as the disappearance of all TLs and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
34.5
(29.0 to 40.3)
47.3
(41.5 to 53.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluoropyrimidine/Cisplatin (FP), Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 12.80
Confidence Interval (2-Sided) 95%
4.7 to 20.9
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Duration of Response - Percentage of Participants With an Event
Hide Description Duration of response was defined for responders as the time from the date on which the CR or PR was first recorded to the date on which PD is first noted. Participants were censored on the date of death, the date of last tumor measurement, the last date in study drug log, or the date of last follow-up.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; only participants with a CR or PR were included in the analysis.
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 100 139
Measure Type: Number
Unit of Measure: percentage of participants
80.0 71.9
9.Secondary Outcome
Title Duration of Response
Hide Description The median time, in months, of the duration of response. Participants were censored at the date of death, the date of last tumor measurement, the last date in study drug log, or the date of last follow-up.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; only participants with a CR or PR were included in the analysis.
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 100 139
Median (95% Confidence Interval)
Unit of Measure: months
4.8
(4 to 6)
6.9
(6 to 8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluoropyrimidine/Cisplatin (FP), Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.40 to 0.73
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With Clinical Benefit
Hide Description Clinical benefit was defined as stable disease (SD), CR, or PR for 6 weeks or longer as determined by RECIST. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as a reference the smallest SLD recorded since treatment had started. For NTLs, SD was defined as a persistence of one or more NTLs and/or maintenance of tumor marker levels above the normal limits.
Time Frame BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
69.3
(63.7 to 74.6)
78.9
(73.8 to 83.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluoropyrimidine/Cisplatin (FP), Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0081
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Clinical Benefit Rate
Estimated Value 9.60
Confidence Interval (2-Sided) 95%
2.4 to 16.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fluoropyrimidine/Cisplatin (FP), Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.66
Confidence Interval (2-Sided) 95%
1.14 to 2.41
Estimation Comments [Not Specified]
11.Secondary Outcome
Title European Organisation For the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ C-30) Questionnaire Scores
Hide Description EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score equals (=) better level of functioning or greater degree of symptoms.
Time Frame BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; n (number) = number of participants assessed for a specific parameter at a given visit.
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Mean (Standard Error)
Unit of Measure: scores on a scale
Global Health Status: BL (n=274,287) 55.3  (1.43) 54.9  (1.30)
Global Health Status: Week 4 (n=235,249) 61.0  (1.37) 60.9  (1.28)
Global Health Status: Week 7 (n=180,220) 60.9  (1.54) 60.5  (1.36)
Global Health Status: Week 10 (n=176,202) 62.3  (1.58) 61.9  (1.42)
Global Health Status: Week 13 (n=152,182) 63.8  (1.77) 63.6  (1.47)
Global Health Status: Week 16 (n=121,165) 60.8  (1.85) 61.9  (1.58)
Global Health Status: Week 19 (n=114,143) 61.0  (1.94) 63.8  (1.80)
Global Health Status: Week 22 (n=78,143) 65.1  (2.32) 64.9  (1.76)
Global Health Status: Week 25 (n=64,124) 68.0  (2.65) 67.8  (2.02)
Global Health Status: Week 28 (n=47,111) 72.0  (2.69) 68.5  (2.08)
Global Health Status: Week 31 (n=45,95) 69.6  (2.83) 70.0  (2.07)
Global Health Status: Week 34 (n=36,87) 70.8  (3.55) 72.0  (2.18)
Global Health Status: Week 37 (n=29,64) 66.1  (3.72) 70.6  (2.41)
Global Health Status: Week 40 (n=23,55) 62.0  (4.97) 70.6  (2.92)
Global Health Status: Week 43 (n=12,43) 72.9  (5.14) 73.6  (3.23)
Global Health Status: Week 46 (n=13,42) 75.0  (4.00) 73.8  (3.18)
Global Health Status: Week 49 (n=9,36) 68.5  (5.69) 76.6  (2.83)
Global Health Status: Week 52 (n=7,29) 72.6  (3.95) 71.3  (4.02)
Global Health Status: Week 55 (n=5,24) 76.7  (4.08) 73.8  (4.68)
Global Health Status: Week 58 (n=5,21) 76.7  (4.08) 73.8  (4.68)
Global Health Status: Week 61 (n=4,17) 79.2  (7.98) 72.5  (5.48)
Global Health Status: Week 64 (n=3,20) 77.8  (5.56) 70.0  (4.85)
Global Health Status: Week 67 (n=4,17) 75.0  (4.81) 72.5  (5.14)
Global Health Status: Week 70 (n=3,14) 77.8  (5.56) 68.5  (5.61)
Global Health Status: Week 73 (n=3,12) 80.6  (2.78) 68.1  (5.97)
Global Health Status: Week 76 (n=3,8) 77.8  (5.56) 67.7  (8.97)
Global Health Status: Week 79 (n=3,9) 77.8  (5.56) 69.4  (7.08)
Global Health Status: Week 82 (n=2,5) 83.3  (0.00) 60.0  (10.34)
Global Health Status: Week 85 (n=2,6) 83.3  (0.00) 79.2  (6.72)
Global Health Status: Week 88 (n=2,6) 83.3  (0.00) 73.6  (5.45)
Global Health Status: Week 91 (n=2,4) 83.3  (0.00) 79.2  (5.38)
Global Health Status: Week 94 (n=2,6) 83.3  (0.00) 79.2  (7.98)
Global Health Status: Week 97 (n=1,5) 83.3 [1]   (NA) 78.3  (3.33)
Global Health Status: Week 100 (n=1,4) 83.3 [1]   (NA) 85.4  (5.24)
Global Health Status: Week 103 (n=1,3) 83.3 [1]   (NA) 75.0  (4.81)
Global Health Status: Week 106 (n=1,4) 83.3 [1]   (NA) 77.1  (3.99)
Global Health Status: Week 109 (n=1,4) 83.3 [1]   (NA) 77.1  (3.99)
Global Health Status: Week 112 (n=1,5) 83.3 [1]   (NA) 75.0  (3.73)
Global Health Status: Week 115 (n=1,4) 83.3 [1]   (NA) 72.9  (3.99)
Global Health Status: Week 118 (n=1,5) 83.3 [1]   (NA) 75.0  (3.73)
Global Health Status: Week 121 (n=1,5) 83.3 [1]   (NA) 75.0  (3.73)
Global Health Status: Week 124 (n=1,5) 83.3 [1]   (NA) 81.7  (5.53)
Global Health Status: Week 127 (n=1,3) 83.3 [1]   (NA) 72.2  (5.56)
Global Health Status: Week 130 (n=0,3) NA [2]   (NA) 72.2  (5.56)
Global Health Status: Week 133 (n=1,3) 83.3 [1]   (NA) 72.2  (5.56)
Global Health Status: Week 136 (n=0,2) NA [2]   (NA) 66.7  (0.00)
Global Health Status: Week 139 (n=0,2) NA [2]   (NA) 66.7  (0.00)
Global Health Status: Week 142 (n=0,2) NA [2]   (NA) 66.7  (0.00)
Global Health Status: Week 145 (n=0,1) NA [2]   (NA) 66.7 [1]   (NA)
Global Health Status: Final Visit (n=158,160) 53.2  (2.09) 53.1  (2.20)
Physical Functioning: BL (n=276,287) 78.9  (1.16) 79.6  (1.17)
Physical Functioning: Week 4 (n=235,250) 76.0  (1.27) 79.5  (1.20)
Physical Functioning: Week 7 (n=181,220) 79.3  (1.37) 79.3  (1.25)
Physical Functioning: Week 10 (n=174,201) 78.2  (1.47) 80.2  (1.22)
Physical Functioning: Week 13 (n=151,183) 80.2  (1.53) 80.5  (1.36)
Physical Functioning: Week 16 (n=121,165) 79.8  (1.58) 80.7  (1.37)
Physical Functioning: Week 19 (n=114,143) 78.8  (1.81) 81.5  (1.49)
Physical Functioning: Week 22 (n=79,143) 80.7  (2.20) 83.6  (1.38)
Physical Functioning: Week 25 (n=64,124) 85.8  (2.07) 84.8  (1.30)
Physical Functioning: Week 28 (n=47,110) 86.2  (2.50) 83.7  (1.60)
Physical Functioning: Week 31 (n=45,95) 85.6  (2.45) 85.4  (1.66)
Physical Functioning: Week 34 (n=37,87) 86.3  (2.50) 85.1  (1.89)
Physical Functioning: Week 37 (n=29,64) 85.7  (3.43) 85.8  (2.05)
Physical Functioning: Week 40 (n=24,55) 84.4  (3.51) 88.2  (1.88)
Physical Functioning: Week 43 (n=12,43) 85.6  (3.75) 89.9  (1.85)
Physical Functioning: Week 46 (n=14,42) 87.6  (3.03) 91.9  (1.53)
Physical Functioning: Week 49 (n=10,36) 88.7  (3.45) 92.0  (1.61)
Physical Functioning: Week 52 (n=8,30) 88.3  (3.93) 89.2  (2.71)
Physical Functioning: Week 55 (n=6,24) 85.6  (5.28) 93.1  (1.90)
Physical Functioning: Week 58 (n=6,21) 86.7  (5.71) 91.4  (2.88)
Physical Functioning: Week 61 (n=4,17) 91.7  (5.00) 91.0  (3.66)
Physical Functioning: Week 64 (n=3,20) 95.6  (4.44) 91.0  (3.36)
Physical Functioning: Week 67 (n=4,17) 93.3  (4.71) 93.3  (2.56)
Physical Functioning: Week 70 (n=3,14) 97.8  (2.22) 92.9  (3.73)
Physical Functioning: Week 73 (n=3,12) 97.8  (2.22) 91.1  (3.70)
Physical Functioning: Week 76 (n=3,8) 95.6  (4.44) 90.0  (5.49)
Physical Functioning: Week 79 (n=3,9) 95.6  (4.44) 92.6  (3.41)
Physical Functioning: Week 82 (n=2,6) 93.3  (6.67) 90.0  (6.38)
Physical Functioning: Week 85 (n=2,6) 100.0  (0.00) 95.6  (2.81)
Physical Functioning: Week 88 (n=2,6) 100.0  (0.00) 95.6  (2.22)
Physical Functioning: Week 91 (n=2,4) 100.0  (0.00) 98.3  (1.67)
Physical Functioning: Week 94 (n=2,6) 100.0  (0.00) 97.8  (2.22)
Physical Functioning: Week 97 (n=1,5) 100.0 [1]   (NA) 97.3  (2.67)
Physical Functioning: Week 100 (n=1,4) 100.0 [1]   (NA) 96.7  (3.33)
Physical Functioning: Week 103 (n=1,4) 100.0 [1]   (NA) 96.7  (3.33)
Physical Functioning: Week 106 (n=1,4) 100.0 [1]   (NA) 98.3  (1.67)
Physical Functioning: Week 109 (n=1,4) 100.0 [1]   (NA) 95.0  (3.19)
Physical Functioning: Week 112 (n=1,5) 93.3 [1]   (NA) 97.3  (2.67)
Physical Functioning: Week 115 (n=1,4) 100.0 [1]   (NA) 93.3  (4.71)
Physical Functioning: Week 118 (n=1,5) 100.0 [1]   (NA) 96.0  (4.00)
Physical Functioning: Week 121 (n=1,5) 100.0 [1]   (NA) 94.7  (3.89)
Physical Functioning: Week 124 (n=1,5) 100.0 [1]   (NA) 96.0  (2.67)
Physical Functioning: Week 127 (n=1,3) 100.0 [1]   (NA) 93.3  (3.85)
Physical Functioning: Week 130 (n=0,3) NA [2]   (NA) 93.3  (6.67)
Physical Functioning: Week 133 (n=1,3) 100.0 [1]   (NA) 95.6  (4.44)
Physical Functioning: Week 136 (n=0,2) NA [2]   (NA) 93.3  (6.67)
Physical Functioning: Week 139 (n=0,2) NA [2]   (NA) 93.3  (6.67)
Physical Functioning: Week 142 (n=0,2) NA [2]   (NA) 93.3  (6.67)
Physical Functioning: Week 145 (n=0,1) NA [2]   (NA) 100.0 [1]   (NA)
Physical Functioning: Final Visit (n=158,161) 72.1  (1.97) 73.8  (2.19)
Role Functioning: BL (n=276,287) 73.2  (1.70) 73.9  (1.68)
Role Functioning: Week 4 (n=234,250) 67.4  (1.85) 76.1  (1.67)
Role Functioning: Week 7 (n=181,220) 70.9  (1.99) 73.3  (1.85)
Role Functioning: Week 10 (n=176,202) 70.2  (2.06) 74.3  (1.87)
Role Functioning: Week 13 (n=152,182) 73.4  (2.11) 75.1  (1.93)
Role Functioning: Week 16 (n=121,165) 72.0  (2.41) 74.6  (1.98)
Role Functioning: Week 19 (n=114,143) 71.1  (2.21) 75.8  (2.10)
Role Functioning: Week 22 (n=79,142) 74.7  (2.81) 79.7  (1.93)
Role Functioning: Week 25 (n=64,124) 81.3  (2.93) 82.4  (1.99)
Role Functioning: Week 28 (n=47,110) 80.5  (3.52) 79.7  (2.17)
Role Functioning: Week 31 (n=45,95) 82.2  (2.87) 81.1  (2.45)
Role Functioning: Week 34 (n=37,87) 83.3  (3.10) 82.2  (2.64)
Role Functioning: Week 37 (n=29,64) 81.6  (4.16) 81.5  (2.90)
Role Functioning: Week 40 (n=24,55) 79.9  (4.91) 82.1  (3.11)
Role Functioning: Week 43 (n=12,43) 80.6  (4.95) 86.8  (2.63)
Role Functioning: Week 46 (n=14,42) 82.1  (4.44) 86.5  (2.74)
Role Functioning: Week 49 (n=10,36) 81.7  (6.78) 88.0  (2.94)
Role Functioning: Week 52 (n=8,30) 85.4  (5.84) 84.4  (3.57)
Role Functioning: Week 55 (n=6,24) 80.6  (5.12) 88.2  (3.68)
Role Functioning: Week 58 (n=6,21) 77.8  (5.56) 89.7  (3.14)
Role Functioning: Week 61 (n=4,17) 83.3  (9.62) 87.3  (4.17)
Role Functioning: Week 64 (n=3,20) 83.3  (9.62) 87.5  (4.17)
Role Functioning: Week 67 (n=4,17) 83.3  (6.80) 90.2  (3.52)
Role Functioning: Week 70 (n=3,14) 88.9  (5.56) 86.9  (5.00)
Role Functioning: Week 73 (n=3,12) 88.9  (5.56) 80.6  (5.36)
Role Functioning: Week 76 (n=3,8) 83.3  (9.62) 81.3  (7.34)
Role Functioning: Week 79 (n=3,9) 83.3  (9.62) 81.5  (7.58)
Role Functioning: Week 82 (n=2,6) 91.7  (8.33) 80.6  (10.90)
Role Functioning: Week 85 (n=2,6) 100.0  (0.00) 91.7  (5.69)
Role Functioning: Week 88 (n=2,6) 91.7  (8.33) 94.4  (5.56)
Role Functioning: Week 91 (n=2,4) 91.7  (8.33) 91.7  (8.33)
Role Functioning: Week 94 (n=2,6) 100.0  (0.00) 100.0  (0.00)
Role Functioning: Week 97 (n=1,5) 83.3 [1]   (NA) 90.0  (6.67)
Role Functioning: Week 100 (n=1,4) 83.3 [1]   (NA) 100.0  (0.00)
Role Functioning: Week 103 (n=1,4) 100.0 [1]   (NA) 100.0  (0.00)
Role Functioning: Week 106 (n=1,4) 100.0 [1]   (NA) 100.0  (0.00)
Role Functioning: Week 109 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Role Functioning: Week 112 (n=1,5) 83.3 [1]   (NA) 93.3  (6.67)
Role Functioning: Week 115 (n=1,4) 100.0 [1]   (NA) 83.3  (9.62)
Role Functioning: Week 118 (n=1,5) 100.0 [1]   (NA) 86.7  (8.16)
Role Functioning: Week 121 (n=1,5) 83.3 [1]   (NA) 90.0  (6.67)
Role Functioning: Week 124 (n=1,5) 83.3 [1]   (NA) 90.0  (6.67)
Role Functioning: Week 127 (n=1,3) 100.0 [1]   (NA) 88.9  (11.11)
Role Functioning: Week 130 (n=0,3) NA [2]   (NA) 88.9  (11.11)
Role Functioning: Week 133 (n=1,3) 100.0 [1]   (NA) 88.9  (11.11)
Role Functioning: Week 136 (n=0,2) NA [2]   (NA) 83.3  (16.67)
Role Functioning: Week 139 (n=0,2) NA [2]   (NA) 83.3  (16.67)
Role Functioning: Week 142 (n=0,2) NA [2]   (NA) 83.3  (16.67)
Role Functioning: Week 145 (n=0,1) NA [2]   (NA) 100.0 [1]   (NA)
Role Functioning: Final Visit (n=158,161) 63.5  (2.46) 68.7  (2.51)
Emotional Functioning: BL (n=276,287) 75.4  (1.26) 73.1  (1.30)
Emotional Functioning: Week 4 (n=235,250) 80.5  (1.25) 77.9  (1.30)
Emotional Functioning: Week 7 (n=180,220) 81.3  (1.39) 80.2  (1.37)
Emotional Functioning: Week 10 (n=176,202) 82.9  (1.39) 81.2  (1.31)
Emotional Functioning: Week 13 (n=152,183) 82.6  (1.48) 80.5  (1.41)
Emotional Functioning: Week 16 (n=121,165) 83.1  (1.81) 81.9  (1.49)
Emotional Functioning: Week 19 (n=114,143) 82.2  (1.95) 82.4  (1.56)
Emotional Functioning: Week 22 (n=79,143) 85.9  (2.06) 84.0  (1.53)
Emotional Functioning: Week 25 (n=64,124) 88.2  (1.97) 84.8  (1.53)
Emotional Functioning: Week 28 (n=47,111) 86.0  (2.37) 85.5  (1.54)
Emotional Functioning: Week 31 (n=45,95) 85.7  (2.24) 85.7  (1.78)
Emotional Functioning: Week 34 (n=37,87) 88.5  (2.29) 85.4  (1.86)
Emotional Functioning: Week 37 (n=29,64) 83.9  (3.43) 86.3  (2.12)
Emotional Functioning: Week 40 (n=24,55) 83.6  (3.99) 86.7  (2.23)
Emotional Functioning: Week 43 (n=12,43) 81.9  (5.21) 87.8  (2.22)
Emotional Functioning: Week 46 (n=14,42) 82.1  (4.44) 87.5  (2.56)
Emotional Functioning: Week 49 (n=10,36) 88.3  (4.16) 91.4  (2.41)
Emotional Functioning: Week 52 (n=8,29) 86.5  (5.88) 88.2  (3.16)
Emotional Functioning: Week 55 (n=6,24) 76.4  (9.23) 88.5  (2.55)
Emotional Functioning: Week 58 (n=6,21) 85.6  (6.27) 88.9  (3.22)
Emotional Functioning: Week 61 (n=4,17) 95.8  (2.41) 90.7  (2.25)
Emotional Functioning: Week 64 (n=3,20) 100  (0.00) 86.3  (3.59)
Emotional Functioning: Week 67 (n=4,17) 95.8  (2.41) 89.2  (3.26)
Emotional Functioning: Week 70 (n=3,14) 97.2  (2.78) 89.3  (4.41)
Emotional Functioning: Week 73 (n=3,12) 94.4  (5.56) 82.9  (5.25)
Emotional Functioning: Week 76 (n=3,8) 100.0  (0.00) 87.5  (6.86)
Emotional Functioning: Week 79 (n=3,9) 97.2  (2.78) 84.3  (7.14)
Emotional Functioning: Week 82 (n=2,6) 95.8  (4.17) 83.3  (13.61)
Emotional Functioning: Week 85 (n=2,6) 95.8  (4.17) 91.7  (5.69)
Emotional Functioning: Week 88 (n=2,6) 100.0  (0.00) 90.3  (3.98)
Emotional Functioning: Week 91 (n=2,4) 100.0  (0.00) 95.8  (4.17)
Emotional Functioning: Week 94 (n=2,6) 100.0  (0.00) 88.9  (5.12)
Emotional Functioning: Week 97 (n=1,5) 100.0 [1]   (NA) 91.7  (5.27)
Emotional Functioning: Week 100 (n=1,4) 100.0 [1]   (NA) 87.5  (4.17)
Emotional Functioning: Week 103 (n=1,4) 100.0 [1]   (NA) 87.5  (5.38)
Emotional Functioning: Week 106 (n=1,4) 100.0 [1]   (NA) 89.6  (3.99)
Emotional Functioning: Week 109 (n=1,4) 100.0 [1]   (NA) 91.7  (4.81)
Emotional Functioning: Week 112 (n=1,5) 100.0 [1]   (NA) 95.0  (3.33)
Emotional Functioning: Week 115 (n=1,4) 100.0 [1]   (NA) 93.8  (3.99)
Emotional Functioning: Week 118 (n=1,5) 100.0 [1]   (NA) 90.0  (4.86)
Emotional Functioning: Week 121 (n=1,5) 100.0 [1]   (NA) 95.0  (3.33)
Emotional Functioning: Week 124 (n=1,5) 100.0 [1]   (NA) 90.0  (6.67)
Emotional Functioning: Week 127 (n=1,3) 100.0 [1]   (NA) 100.0  (0.00)
Emotional Functioning: Week 130 (n=0,3) NA [2]   (NA) 88.9  (11.11)
Emotional Functioning: Week 133 (n=1,3) 100.0 [1]   (NA) 91.7  (8.33)
Emotional Functioning: Week 136 (n=0,2) NA [2]   (NA) 95.8  (4.17)
Emotional Functioning: Week 139 (n=0,2) NA [2]   (NA) 95.8  (4.17)
Emotional Functioning: Week 142 (n=0,2) NA [2]   (NA) 95.8  (4.17)
Emotional Functioning: Week 145 (n=0,1) NA [2]   (NA) 100.0 [1]   (NA)
Emotional Functioning: Final Visit (n=158,161) 75.1  (2.16) 74.3  (2.00)
Cognitive Functioning: BL (n=276,287) 86.9  (1.06) 85.7  (1.20)
Cognitive Functioning: Week 4 (n=235,250) 86.0  (1.14) 86.3  (1.14)
Cognitive Functioning: Week 7 (n=180,220) 85.7  (1.36) 86.5  (1.24)
Cognitive Functioning: Week 10 (n=176,202) 85.6  (1.35) 86.8  (1.22)
Cognitive Functioning: Week 13 (n=152,183) 88.2  (1.34) 85.7  (1.43)
Cognitive Functioning: Week 16 (n=121,165) 82.8  (1.70) 86.8  (1.48)
Cognitive Functioning: Week 19 (n=114,143) 84.2  (1.62) 87.6  (1.40)
Cognitive Functioning: Week 22 (n=79,143) 85.9  (1.92) 87.4  (1.53)
Cognitive Functioning: Week 25 (n=64,124) 85.9  (2.20) 87.4  (1.50)
Cognitive Functioning: Week 28 (n=47,111) 86.5  (2.25) 88.0  (1.54)
Cognitive Functioning: Week 31 (n=45,95) 87.0  (2.18) 90.0  (1.66)
Cognitive Functioning: Week 34 (n=37,87) 88.3  (2.49) 88.7  (1.69)
Cognitive Functioning: Week 37 (n=29,64) 88.5  (2.63) 91.4  (1.89)
Cognitive Functioning: Week 40 (n=24,55) 83.3  (3.48) 91.5  (1.93)
Cognitive Functioning: Week 43 (n=12,43) 88.9  (3.75) 91.5  (2.10)
Cognitive Functioning: Week 46 (n=14,42) 89.3  (3.75) 91.7  (2.14)
Cognitive Functioning: Week 49 (n=10,36) 85.0  (5.80) 92.6  (2.43)
Cognitive Functioning: Week 52 (n=8,29) 91.7  (5.46) 89.7  (3.35)
Cognitive Functioning: Week 55 (n=6,24) 94.4  (5.56) 91.0  (2.65)
Cognitive Functioning: Week 58 (n=6,21) 91.7  (5.69) 90.5  (3.37)
Cognitive Functioning: Week 61 (n=4,17) 91.7  (8.33) 91.2  (3.53)
Cognitive Functioning: Week 64 (n=3,20) 100.0  (0.00) 93.3  (3.29)
Cognitive Functioning: Week 67 (n=4,17) 91.7  (8.33) 91.2  (4.07)
Cognitive Functioning: Week 70 (n=3,14) 100.0  (0.00) 91.7  (4.19)
Cognitive Functioning: Week 73 (n=3,12) 100.0  (0.00) 83.3  (4.59)
Cognitive Functioning: Week 76 (n=3,8) 100.0  (0.00) 83.3  (8.33)
Cognitive Functioning: Week 79 (n=3,9) 100.0  (0.00) 81.5  (7.58)
Cognitive Functioning: Week 82 (n=2,6) 100.0  (0.00) 88.9  (5.56)
Cognitive Functioning: Week 85 (n=2,6) 100.0  (0.00) 91.7  (5.69)
Cognitive Functioning: Week 88 (n=2,6) 100.0  (0.00) 94.4  (3.51)
Cognitive Functioning: Week 91 (n=2,4) 100.0  (0.00) 95.8  (4.17)
Cognitive Functioning: Week 94 (n=2,6) 100.0  (0.00) 94.4  (3.51)
Cognitive Functioning: Week 97 (n=1,5) 100.0 [1]   (NA) 90.0  (6.67)
Cognitive Functioning: Week 100 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Cognitive Functioning: Week 103 (n=1,4) 100.0 [1]   (NA) 91.7  (4.81)
Cognitive Functioning: Week 106 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Cognitive Functioning: Week 109 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Cognitive Functioning: Week 112 (n=1,5) 100.0 [1]   (NA) 93.3  (4.08)
Cognitive Functioning: Week 115 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Cognitive Functioning: Week 118 (n=1,5) 100.0 [1]   (NA) 96.7  (3.33)
Cognitive Functioning: Week 121 (n=1,5) 100.0 [1]   (NA) 96.7  (3.33)
Cognitive Functioning: Week 124 (n=1,5) 100.0 [1]   (NA) 96.7  (3.33)
Cognitive Functioning: Week 127 (n=1,3) 100.0 [1]   (NA) 100.0  (0.00)
Cognitive Functioning: Week 130 (n=0,3) NA [2]   (NA) 88.9  (11.11)
Cognitive Functioning: Week 133 (n=1,3) 100.0 [1]   (NA) 94.4  (5.56)
Cognitive Functioning: Week 136 (n=0,2) NA [2]   (NA) 100.0  (0.00)
Cognitive Functioning: Week 139 (n=0,2) NA [2]   (NA) 100.0  (0.00)
Cognitive Functioning: Week 142 (n=0,2) NA [2]   (NA) 100.0  (0.00)
Cognitive Functioning: Week 145 (n=0,1) NA [2]   (NA) 100.0 [1]   (NA)
Cognitive Functioning: Final Visit (n=158,161) 79.5  (1.82) 80.0  (2.05)
Social Functioning: BL (n=276,286) 72.4  (1.63) 72.0  (1.77)
Social Functioning: Week 4 (n=235,250) 72.1  (1.66) 74.1  (1.67)
Social Functioning: Week 7 (n=179,220) 73.1  (1.88) 75.1  (1.70)
Social Functioning: Week 10 (n=176,202) 74.5  (1.84) 76.7  (1.65)
Social Functioning: Week 13 (n=152,183) 72.7  (2.11) 76.3  (1.90)
Social Functioning: Week 16 (n=180,165) 72.7  (2.52) 77.5  (1.88)
Social Functioning: Week 19 (n=114,143) 74.4  (2.41) 79.5  (1.93)
Social Functioning: Week 22 (n=79,143) 79.3  (2.77) 80.1  (2.03)
Social Functioning: Week 25 (n=64,124) 83.3  (2.43) 80.2  (1.78)
Social Functioning: Week 28 (n=47,111) 83.0  (3.38) 80.2  (2.05)
Social Functioning: Week 31 (n=45,95) 81.5  (3.90) 78.9  (2.42)
Social Functioning: Week 34 (n=37,87) 84.7  (3.06) 80.7  (2.45)
Social Functioning: Week 37 (n=29,64) 85.1  (4.48) 81.8  (2.59)
Social Functioning: Week 40 (n=24,55) 85.4  (4.05) 82.7  (2.73)
Social Functioning: Week 43 (n=12,43) 87.5  (4.64) 84.1  (2.77)
Social Functioning: Week 46 (n=14,42) 86.9  (4.34) 86.9  (2.70)
Social Functioning: Week 49 (n=10,36) 85.0  (5.24) 84.7  (3.00)
Social Functioning: Week 52 (n=8,29) 87.5  (6.10) 82.2  (3.87)
Social Functioning: Week 55 (n=6,24) 86.1  (6.69) 85.4  (3.80)
Social Functioning: Week 58 (n=6,21) 88.9  (5.56) 87.3  (4.13)
Social Functioning: Week 61 (n=4,17) 91.7  (4.81) 90.2  (3.52)
Social Functioning: Week 64 (n=3,20) 94.4  (5.56) 85.8  (3.68)
Social Functioning: Week 67 (n=4,17) 95.8  (4.17) 85.3  (4.71)
Social Functioning: Week 70 (n=3,14) 94.4  (5.56) 86.9  (4.34)
Social Functioning: Week 73 (n=3,12) 100.0  (0.00) 80.6  (5.36)
Social Functioning: Week 76 (n=3,8) 94.4  (5.56) 81.3  (7.34)
Social Functioning: Week 79 (n=3,9) 94.4  (5.56) 85.2  (7.58)
Social Functioning: Wek 82 (n=2,6) 100.0  (0.00) 80.6  (6.69)
Social Functioning: Week 85 (n=2,6) 91.7  (8.33) 88.9  (7.03)
Social Functioning: Week 88 (n=2,6) 91.7  (8.33) 88.9  (5.56)
Social Functioning: Week 91 (n=2,4) 100.0  (0.00) 91.7  (8.33)
Social Functioning: Week 94 (n=2,6) 100.0  (0.00) 91.7  (5.69)
Social Functioning: Week 97 (n=1,5) 100.0 [1]   (NA) 90.0  (6.67)
Social Functioning: Week 100 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Social Functioning: Week 103 (n=1,4) 100.0 [1]   (NA) 100.0  (0.00)
Social Functioning: Week 106 (n=1,4) 100.0 [1]   (NA) 91.7  (8.33)
Social Functioning: Week 109 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Social Functioning: Week 112 (n=1,5) 100.0 [1]   (NA) 96.7  (3.33)
Social Functioning: Week 115 (n=1,4) 100.0 [1]   (NA) 95.8  (4.17)
Social Functioning: Week 118 (n=1,5) 100.0 [1]   (NA) 96.7  (3.33)
Social Functioning: Week 121 (n=1,5) 100.0 [1]   (NA) 100.0  (0.00)
Social Functioning: Week 124 (n=1,5) 100.0 [1]   (NA) 96.7  (3.33)
Social Functioning: Week 127 (n=1,3) 100.0 [1]   (NA) 83.3  (9.62)
Social Functioning: Week 130 (n=0,3) NA [2]   (NA) 94.4  (5.56)
Social Functioning: Week 133 (n=1,3) 100.0 [1]   (NA) 100.0  (0.00)
Social Functioning: Week 136 (n=0,2) NA [2]   (NA) 100.0  (0.00)
Social Functioning: Week 139 (n=0,2) NA [2]   (NA) 100.0  (0.00)
Social Functioning: Week 142 (n=0,2) NA [2]   (NA) 100.0  (0.00)
Social Functioning: Week 145 (n=0,1) NA [2]   (NA) 100.0 [1]   (NA)
Social Functioning: Final Visit (n=158,161) 68.1  (2.41) 71.4  (2.39)
Fatigue: BL (n=276,287) 36.3  (1.37) 34.2  (1.41)
Fatigue: Week 4 (n=235,250) 37.1  (1.47) 34.5  (1.34)
Fatigue: Week 7 (n=181,220) 34.4  (1.54) 34.1  (1.48)
Fatigue: Week 10 (n=176,201) 35.3  (1.70) 33.2  (1.50)
Fatigue: Week 13 (n=152,183) 32.9  (1.70) 33.7  (1.71)
Fatigue: Week 16 (n=121,165) 33.0  (2.09) 32.8  (1.76)
Fatigue: Week 19 (n=114,143) 33.1  (2.11) 29.4  (1.87)
Fatigue: Week 22 (n=79,143) 30.0  (2.63) 26.7  (1.76)
Fatigue: Week 25 (n=64,124) 22.2  (2.55) 25.1  (1.90)
Fatigue: Week 28 (n=47,110) 24.1  (3.16) 23.2  (1.93)
Fatigue: Week 31 (n=45,95) 22.0  (2.92) 22.2  (2.17)
Fatigue: Week 34 (n=37,87) 22.8  (3.63) 19.7  (2.28)
Fatigue: Week 37 (n=29,64) 21.8  (4.63) 19.8  (2.52)
Fatigue: Week 40 (n=24,55) 23.6  (4.45) 18.6  (2.33)
Fatigue: Week 43 (n=12,43) 19.4  (3.90) 17.1  (2.68)
Fatigue: Week 46 (n=14,42) 20.6  (4.18) 13.8  (2.36)
Fatigue: Week 49 (n=10,36) 19.4  (3.23) 14.5  (2.38)
Fatigue: Week 52 (n=8,30) 16.7  (2.97) 17.2  (3.48)
Fatigue: Week 55 (n=6,24) 18.5  (5.49) 14.4  (3.75)
Fatigue: Week 58 (n=6,21) 16.7  (4.76) 16.4  (3.22)
Fatigue: Week 61 (n=4,17) 8.3  (5.32) 14.4  (3.53)
Fatigue: Week 64 (n=3,20) 7.4  (3.70) 17.2  (4.15)
Fatigue: Week 67 (n=4,17) 13.9  (2.78) 15.0  (4.04)
Fatigue: Week 70 (n=3,14) 11.1  (0.00) 16.7  (5.04)
Fatigue: Week 73 (n=3,12) 7.4  (3.70) 16.7  (5.38)
Fatigue: Week 76 (n=3,8) 7.4  (3.70) 18.1  (6.94)
Fatigue: Week 79 (n=3,9) 7.4  (3.70) 18.5  (7.64)
Fatigue: Week 82 (n=2,6) 0.0  (0.00) 29.6  (8.92)
Fatigue: Week 85 (n=2,6) 5.6  (5.56) 11.1  (5.74)
Fatigue: Week 88 (n=2,6) 0.0  (0.00) 9.3  (3.41)
Fatigue: Week 91 (n=2,4) 0.0  (0.00) 11.1  (7.86)
Fatigue: Week 94 (n=2,6) 0.0  (0.00) 7.4  (5.49)
Fatigue: Week 97 (n=1,5) 11.1 [1]   (NA) 11.1  (6.09)
Fatigue: Week 100 (n=1,4) 0.0 [1]   (NA) 11.1  (7.86)
Fatigue: Week 103 (n=1,4) 0.0 [1]   (NA) 19.4  (5.32)
Fatigue: Week 106 (n=1,4) 11.1 [1]   (NA) 13.9  (6.99)
Fatigue: Week 109 (n=1,4) 0.0 [1]   (NA) 16.7  (7.17)
Fatigue: Week 112 (n=1,5) 0.0 [1]   (NA) 17.8  (6.67)
Fatigue: Week 115 (n=1,4) 0.0 [1]   (NA) 25.0  (5.32)
Fatigue: Week 118 (n=1,5) 0.0 [1]   (NA) 17.8  (6.67)
Fatigue: Week 121 (n=1,5) 0.0 [1]   (NA) 17.8  (6.67)
Fatigue: Week 124 (n=1,5) 0.0 [1]   (NA) 13.3  (6.48)
Fatigue: Week 127 (n=1,3) 0.0 [1]   (NA) 14.8  (9.80)
Fatigue: Week 130 (n=0,3) NA [2]   (NA) 18.5  (7.41)
Fatigue: Week 133 (n=1,3) 0.0 [1]   (NA) 14.8  (9.80)
Fatigue: Week 136 (n=0,2) NA [2]   (NA) 22.2  (11.11)
Fatigue: Week 139 (n=0,2) NA [2]   (NA) 22.2  (11.11)
Fatigue: Week 142 (n=0,2) NA [2]   (NA) 22.2  (11.11)
Fatigue: Week 145 (n=0,1) NA [2]   (NA) 11.1 [1]   (NA)
Fatigue: Final Visit (n=158,160) 40.4  (2.17) 37.6  (2.31)
Nausea & Vomiting: BL (n=276,287) 15.0  (1.39) 15.7  (1.36)
Nausea & Vomiting: Week 4 (n=235,250) 16.6  (1.45) 19.7  (1.46)
Nausea & Vomiting: Week 7 (n=181,220) 16.9  (1.66) 18.9  (1.63)
Nausea & Vomiting: Week 10 (n=176,201) 16.4  (1.67) 16.4  (1.56)
Nausea & Vomiting: Week 13 (n=121,183) 12.8  (1.41) 14.7  (1.55)
Nausea & Vomiting: Week 16 (n=121,165) 14.2  (1.99) 14.5  (1.56)
Nausea & Vomiting: Week 19 (n=114,143) 14.2  (2.01) 13.9  (1.59)
Nausea & Vomiting: Week 22 (n=79,143) 10.3  (2.23) 12.2  (1.66)
Nausea & Vomiting: Week 25 (n=64,124) 8.6  (2.38) 8.2  (1.48)
Nausea & Vomiting: Week 28 (n=47,110) 3.5  (1.34) 6.5  (1.52)
Nausea & Vomiting: Week 31 (n=45,95) 3.7  (1.58) 8.8  (2.02)
Nausea & Vomiting: Week 34 (n=37,87) 4.5  (1.90) 7.5  (1.90)
Nausea & Vomiting: Week 37 (n=29,64) 2.9  (1.67) 6.8  (2.34)
Nausea & Vomiting: Week 40 (n=24,55) 4.2  (1.50) 4.8  (1.87)
Nausea & Vomiting: Week 43 (n=12,43) 2.8  (1.87) 1.2  (0.66)
Nausea & Vomiting: Week 46 (n=14,42) 1.2  (1.19) 2.8  (1.12)
Nausea & Vomiting: Week 49 (n=10,36) 3.3  (2.22) 0.9  (0.65)
Nausea & Vomiting: Week 52 (n=8,30) 2.1  (2.08) 5.0  (2.90)
Nausea & Vomiting: Week 55 (n=6,24) 0.0  (0.00) 2.1  (1.15)
Nausea & Vomiting: Week 58 (n=6,21) 0.0  (0.00) 3.2  (2.19)
Nausea & Vomiting: Week 61 (n=4,17) 0.0  (0.00) 0.0  (0.00)
Nausea & Vomiting: Week 64 (n=3,20) 0.0  (0.00) 4.2  (2.38)
Nausea & Vomiting: Week 67 (n=4,17) 0.0  (0.00) 2.9  (2.14)
Nausea & Vomiting: Week 70 (n=3,14) 0.0  (0.00) 2.4  (2.38)
Nausea & Vomiting: Week 73 (n=3,12) 0.0  (0.00) 1.4  (1.39)
Nausea & Vomiting: Week 76 (n=3,8) 5.6  (5.56) 0.0  (0.00)
Nausea & Vomiting: Week 79 (n=3,9) 0.0  (0.00) 0.0  (0.00)
Nausea & Vomiting: Week 82 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Nausea & Vomiting: Week 85 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Nausea & Vomiting: Week 88 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Nausea & Vomiting: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Nausea & Vomiting: Week 94 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Nausea & Vomiting: Week 97 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 112 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 118 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Nausea & Vomiting: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Nausea & Vomiting: Final Visit (n=158,161) 14.9  (1.79) 19.8  (2.36)
Pain: BL (n=276,287) 24.9  (1.46) 25.1  (1.55)
Pain: Week 4 (n=235,250) 17.8  (1.43) 17.9  (1.30)
Pain: Week 7 (n=181,220) 14.5  (1.43) 16.1  (1.50)
Pain: Week 10 (n=176,202) 13.4  (1.34) 14.4  (1.42)
Pain: Week 13 (n=152,183) 12.0  (1.42) 13.3  (1.45)
Pain: Week 16 (n=121,165) 13.6  (1.80) 12.4  (1.54)
Pain: Week 19 (n=114,143) 14.2  (1.98) 12.8  (1.68)
Pain: Week 22 (n=79,143) 15.0  (2.59) 13.2  (1.80)
Pain: Week 25 (n=64,124) 10.7  (2.44) 12.2  (1.90)
Pain: Week 28 (n=47,111) 8.2  (1.82) 12.0  (1.97)
Pain: Week 31 (n=45,95) 12.2  (2.97) 11.8  (2.22)
Pain: Week 34 (n=37,87) 12.2  (3.00) 11.3  (2.32)
Pain: Week 37 (n=29,64) 11.5  (2.99) 12.2  (2.90)
Pain: Week 40 (n=24,55) 18.8  (4.74) 10.3  (2.75)
Pain: Week 43 (n=12,43) 16.7  (5.03) 8.9  (2.44)
Pain: Week 46 (n=14,42) 13.1  (3.57) 6.7  (2.48)
Pain: Week 49 (n=10,36) 13.3  (4.84) 6.5  (2.23)
Pain: Week 52 (n=8,30) 6.3  (3.05) 10.0  (4.49)
Pain: Week 55 (n=6,24) 2.8  (2.78) 8.3  (4.01)
Pain: Week 58 (n=6,21) 8.3  (5.69) 7.1  (3.56)
Pain: Week 61 (n=4,17) 0.0  (0.00) 4.9  (3.43)
Pain: Week 64 (n=3,20) 5.6  (5.56) 6.7  (3.06)
Pain: Week 67 (n=4,17) 0.0  (0.00) 4.9  (2.77)
Pain: Week 70 (n=3,14) 0.0  (0.00) 4.8  (4.76)
Pain: Week 73 (n=3,12) 5.6  (5.56) 9.7  (5.97)
Pain: Week 76 (n=3,8) 5.6  (5.56) 8.3  (8.33)
Pain: Week 79 (n=3,9) 5.6  (5.56) 9.3  (7.41)
Pain: Week 82 (n=2,6) 0.0  (0.00) 2.8  (2.78)
Pain: Week 85 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Pain: Week 88 (n=2,6) 0.0  (0.00) 2.8  (2.78)
Pain: Week 91 (n=2,4) 0.0  (0.00) 4.2  (4.17)
Pain: Week 94 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Pain: Week 97 (n=1,5) 0.0 [1]   (NA) 3.3  (3.33)
Pain: Week 100 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Pain: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Pain: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Pain: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Pain: Week 112 (n=1,5) 0.0 [1]   (NA) 3.3  (3.33)
Pain: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Pain: Week 118 (n=1,5) 0.0 [1]   (NA) 3.3  (3.33)
Pain: Week 121 (n=1,5) 0.0 [1]   (NA) 3.3  (3.33)
Pain: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Pain: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Pain: Week 130 (n=0,3) NA [2]   (NA) 5.6  (5.56)
Pain: Week 133 (n=1,3) 0.0 [1]   (NA) 5.6  (5.56)
Pain: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Pain: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Pain: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Pain: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Pain: Final Visit (n=158,161) 27.4  (2.34) 25.4  (2.49)
Dyspnoea: BL (n=274,281) 12.4  (1.25) 13.4  (1.23)
Dyspnoea: Week 4 (n=232,249) 12.1  (1.35) 11.8  (1.24)
Dyspnoea: Week 7 (n=181,217) 12.7  (1.66) 10.8  (1.21)
Dyspnoea: Week 10 (n=176,198) 14.6  (1.71) 11.3  (1.33)
Dyspnoea: Week 13 (n=151,182) 11.3  (1.80) 13.7  (1.74)
Dyspnoea: Week 16 (n=121,165) 15.4  (2.28) 13.5  (1.79)
Dyspnoea: Week 19 (n=113,143) 15.3  (2.48) 11.9  (1.70)
Dyspnoea: Week 22 (n=79,143) 13.9  (2.79) 12.1  (1.64)
Dyspnoea: Week 25 (n=63,124) 12.7  (2.76) 9.4  (1.60)
Dyspnoea: Week 28 (n=47,110) 9.2  (2.42) 10.3  (1.76)
Dyspnoea: Week 31 (n=45,95) 10.4  (2.56) 9.1  (1.69)
Dyspnoea: Week 34 (n=36,87) 10.2  (2.92) 9.6  (2.10)
Dyspnoea: Week 37 (n=29,64) 10.3  (3.35) 10.4  (2.45)
Dyspnoea: Week 40 (n=24,55) 9.7  (3.74) 4.8  (1.60)
Dyspnoea: Week 43 (n=12,43) 19.4  (7.63) 6.2  (2.00)
Dyspnoea: Week 46 (n=14,42) 11.9  (4.43) 5.6  (1.94)
Dyspnoea: Week 49 (n=10,36) 6.7  (4.44) 4.6  (1.95)
Dyspnoea: Week 52 (n=8,30) 12.5  (6.10) 5.6  (2.31)
Dyspnoea: Week 55 (n=6,24) 5.6  (5.56) 8.3  (3.01)
Dyspnoea: Week 58 (n=6,21) 5.6  (5.56) 6.3  (3.72)
Dyspnoea: Week 61 (n=4,17) 16.7  (9.62) 3.9  (2.68)
Dyspnoea: Week 64 (n=3,20) 0.0  (0.00) 8.3  (4.10)
Dyspnoea: Week 67 (n=4,17) 8.3  (8.33) 5.9  (4.27)
Dyspnoea: Week 70 (n=3,14) 0.0  (0.00) 7.1  (5.16)
Dyspnoea: Week 73 (n=3,12) 0.0  (0.00) 8.3  (4.35)
Dyspnoea: Week 76 (n=3,8) 11.1  (11.11) 8.3  (5.46)
Dyspnoea: Week 79 (n=3,9) 0.0  (0.00) 7.4  (4.90)
Dyspnoea: Week 82 (n=2,6) 0.0  (0.00) 16.7  (11.39)
Dyspnoea: Week 85 (n=180,6) 0.0  (0.00) 5.6  (5.56)
Dyspnoea: Week 88 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Dyspnoea: Week 91 (n=2,4) 0.0  (0.00) 8.3  (8.33)
Dyspnoea: Week 94 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Dyspnoea: Week 97 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dyspnoea: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dyspnoea: Week 103 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Dyspnoea: Week 106 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Dyspnoea: Week 109 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Dyspnoea: Week 112 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Dyspnoea: Week 115 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Dyspnoea: Week 118 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Dyspnoea: Week 121 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Dyspnoea: Week 124 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Dyspnoea: Week 127 (n=1,3) 0.0 [1]   (NA) 11.1  (11.11)
Dyspnoea: Week 130 (n=0,3) NA [2]   (NA) 11.1  (11.11)
Dyspnoea: Week 133 (n=1,3) 0.0 [1]   (NA) 11.1  (11.11)
Dyspnoea: Week 136 (n=0,2) NA [2]   (NA) 16.7  (16.67)
Dyspnoea: Week 139 (n=0,2) NA [2]   (NA) 16.7  (16.67)
Dyspnoea: Week 142 (n=0,2) NA [2]   (NA) 16.7  (16.67)
Dyspnoea: Week 145 (n=0,1) NA [2]   (NA) 33.3 [1]   (NA)
Dyspnoea: Final Visit (n=157,160) 20.0  (2.13) 18.3  (2.11)
Insomnia: BL (n=276,285) 27.2  (1.86) 23.6  (1.71)
Insomnia: Week 4 (n=234,248) 22.1  (1.82) 23.3  (1.65)
Insomnia: Week 7 (n=181,219) 21.9  (2.10) 20.4  (1.69)
Insomnia: Week 10 (n=175,200) 19.8  (2.04) 18.0  (1.63)
Insomnia: Week 13 (n=152,183) 14.7  (1.86) 18.9  (1.70)
Insomnia: Week 16 (n=120,164) 15.3  (1.93) 17.7  (1.88)
Insomnia: Week 19 (n=113,143) 17.1  (2.30) 20.0  (2.10)
Insomnia: Week 22 (n=79,143) 14.8  (2.38) 17.0  (2.24)
Insomnia: Week 25 (n=64,124) 15.1  (3.05) 15.9  (2.14)
Insomnia: Week 28 (n=47,110) 9.9  (3.03) 13.3  (2.07)
Insomnia: Week 31 (n=45,94) 10.4  (2.77) 14.9  (2.34)
Insomnia: Week 34 (n=37,87) 9.0  (2.78) 13.4  (2.07)
Insomnia: Week 37 (n=29,63) 8.0  (3.16) 11.1  (2.26)
Insomnia: Week 40 (n=24,55) 13.9  (4.45) 10.3  (2.58)
Insomnia: Week 43 (n=12,43) 13.9  (8.66) 9.3  (2.79)
Insomnia: Week 46 (n=13,42) 7.7  (4.05) 9.5  (2.85)
Insomnia: Week 49 (n=10,36) 10.0  (7.11) 7.4  (2.69)
Insomnia: Week 52 (n=8,30) 12.5  (6.10) 7.8  (3.07)
Insomnia: Week 55 (n=6,24) 16.7  (7.45) 8.3  (3.01)
Insomnia: Week 58 (n=6,21) 11.1  (7.03) 9.5  (4.08)
Insomnia: Week 61 (n=4,17) 8.3  (8.33) 7.8  (4.55)
Insomnia: Week 64 (n=3,20) 0.0  (0.00) 10.0  (4.90)
Insomnia: Week 67 (n=4,17) 0.0  (0.00) 9.8  (4.75)
Insomnia: Week 70 (n=3,14) 0.0  (0.00) 9.5  (5.45)
Insomnia: Week 73 (n=3,12) 0.0  (0.00) 11.1  (6.27)
Insomnia: Week 76 (n=3,8) 0.0  (0.00) 8.3  (5.46)
Insomnia: Week 79 (n=3,9) 0.0  (0.00) 11.1  (5.56)
Insomnia: Week 82 (n=2,6) 0.0  (0.00) 11.1  (11.11)
Insomnia: Week 85 (n=2,6) 0.0  (0.00) 11.1  (7.03)
Insomnia: Week 88 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Insomnia: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Insomnia: Week 94 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Insomnia: Week 97 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Insomnia: Week 100 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Insomnia: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Insomnia: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Insomnia: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Insomnia: Week 112 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Insomnia: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Insomnia: Week 118 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Insomnia: Week 121 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Insomnia: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Insomnia: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Insomnia: Week 130 (n=0,3) NA [2]   (NA) 11.1  (11.11)
Insomnia: Week 133 (n=1,3) 0.0 [1]   (NA) 11.1  (11.11)
Insomnia: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Insomnia: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Insomnia: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Insomnia: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Insomnia: Final Visit (n=157,160) 21.9  (2.29) 24.6  (2.28)
Appetite Loss: BL (n=275,286) 35.2  (2.02) 33.8  (2.04)
Appetite Loss: Week 4 (n=235,250) 31.5  (2.01) 33.6  (2.01)
Appetite Loss: Week 7 (n=180,216) 27.2  (2.19) 31.3  (2.04)
Appetite Loss: Week 10 (n=176,201) 26.7  (2.10) 29.4  (2.08)
Appetite Loss: Week 13 (n=151,183) 24.7  (2.11) 28.4  (2.17)
Appetite Loss: Week 16 (n=121,165) 24.5  (2.27) 27.9  (2.23)
Appetite Loss: Week 19 (n=114,141) 26.9  (2.81) 25.1  (2.40)
Appetite Loss: Week 22 (n=79,143) 19.0  (2.92) 20.7  (2.19)
Appetite Loss: Week 25 (n=64,124) 12.0  (2.39) 16.7  (1.96)
Appetite Loss: Week 28 (n=47,109) 14.2  (2.82) 11.6  (1.96)
Appetite Loss: Week 31 (n=45,95) 11.1  (3.18) 13.0  (2.61)
Appetite Loss: Week 34 (n=37,87) 11.7  (2.65) 9.6  (2.24)
Appetite Loss: Week 37 (n=29,64) 12.6  (3.48) 10.9  (2.78)
Appetite Loss: Week 40 (n=24,55) 13.9  (3.97) 9.7  (2.69)
Appetite Loss: Week 43 (n=12,43) 5.6  (3.75) 7.0  (2.37)
Appetite Loss: Week 46 (n=14,42) 4.8  (3.24) 5.6  (2.25)
Appetite Loss: Week 49 (n=9,36) 3.7  (3.70) 6.5  (2.23)
Appetite Loss: Week 52 (n=8,30) 0.0  (0.00) 10.0  (3.96)
Appetite Loss: Week 55 (n=6,24) 0.0  (0.00) 10.0  (3.96)
Appetite Loss: Week 58 (n=6,21) 5.6  (5.56) 4.8  (2.61)
Appetite Loss: Week 61 (n=4,17) 8.3  (8.33) 0.0  (0.00)
Appetite Loss: Week 64 (n=3,20) 0.0  (0.00) 8.3  (4.10)
Appetite Loss: Week 67 (n=4,17) 8.3  (8.33) 5.9  (3.18)
Appetite Loss: Week 70 (n=3,14) 0.0  (0.00) 7.1  (5.16)
Appetite Loss: Week 73 (n=3,12) 0.0  (0.00) 5.6  (3.75)
Appetite Loss: Week 76 (n=3,8) 0.0  (0.00) 4.2  (4.17)
Appetite Loss: Week 79 (n=3,9) 0.0  (0.00) 0.0  (0.00)
Appetite Loss: Week 82 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Appetite Loss: Week 85 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Appetite Loss: Week 88 (n=2,6) 0.0  (0.00) 11.1  (7.03)
Appetite Loss: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Appetite Loss: Week 94 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Appetite Loss: Week 97 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 103 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Appetite Loss: Week 106 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Appetite Loss: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 112 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 118 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Appetite Loss: Week 130 (n=0,3) NA [2]   (NA) 11.1  (11.11)
Appetite Loss: Week 133 (n=1,3) 0.0 [1]   (NA) 11.1  (11.11)
Appetite Loss: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Appetite Loss: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Appetite Loss: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Appetite Loss: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Appetite Loss: Week Final Visit (n=156,161) 35.3  (2.45) 33.5  (2.76)
Constipation: BL (n=276,285) 22.9  (1.79) 21.5  (1.69)
Constipation: Week 4 (n=235,247) 20.6  (1.85) 20.2  (1.76)
Constipation: Week 7 (n=179,220) 19.0  (2.01) 17.6  (1.79)
Constipation: Week 10 (n=175,203) 19.2  (1.90) 15.1  (1.68)
Constipation: Week 13 (n=152,183) 16.7  (1.92) 15.8  (1.73)
Constipation: Week 16 (n=121,165) 14.6  (1.99) 15.4  (1.87)
Constipation: Week 19 (n=114,143) 13.5  (2.11) 14.5  (1.94)
Constipation: Week 22 (n=78,143) 12.0  (2.27) 10.0  (1.62)
Constipation: Week 25 (n=64,124) 7.3  (2.40) 10.2  (1.71)
Constipation: Week 28 (n=47,111) 7.8  (2.31) 9.6  (1.93)
Constipation: Week 31 (n=45,95) 10.4  (2.96) 6.3  (1.68)
Constipation: Week 34 (n=37,86) 5.4  (2.05) 4.7  (1.48)
Constipation: Week 37 (n=29,64) 11.5  (3.80) 10.4  (2.96)
Constipation: Week 40 (n=24,55) 8.3  (3.62) 7.9  (2.28)
Constipation: Week 43 (n=12,43) 8.3  (4.35) 7.0  (2.37)
Constipation: Week 46 (n=14,42) 4.8  (3.24) 7.1  (2.90)
Constipation: Week 49 (n=10,36) 3.3  (3.33) 5.6  (2.10)
Constipation: Week 52 (n=8,29) 4.2  (4.17) 10.3  (4.09)
Constipation: Week 55 (n=6,24) 5.6  (5.56) 6.9  (4.48)
Constipation: Week 58 (n=6,21) 11.1  (7.03) 6.3  (3.72)
Constipation: Week 61 (n=4,17) 8.3  (8.33) 5.9  (4.27)
Constipation: Week 64 (n=3,20) 0.0  (0.00) 5.0  (3.65)
Constipation: Week 67 (n=4,17) 0.0  (0.00) 5.9  (4.27)
Constipation: Week 70 (n=3,14) 0.0  (0.00) 4.8  (4.76)
Constipation: Week 73 (n=3,12) 0.0  (0.00) 11.1  (6.27)
Constipation: Week 76 (n=3,8) 0.0  (0.00) 4.2  (4.17)
Constipation: Week 79 (n=3,9) 0.0  (0.00) 3.7  (3.70)
Constipation: Week 82 (n=2,6) 16.7  (16.67) 16.7  (16.67)
Constipation: Week 85 (n=2,6) 16.7  (16.67) 0.0  (0.00)
Constipation: Week 88 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Constipation: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Constipation: Week 94 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Constipation: Week 97 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 112 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 118 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Constipation: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Constipation: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Constipation: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Constipation: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Constipation: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Constipation: Final Visit (n=158,160) 19.0  (2.12) 20.0  (2.16)
Diarrhoea: BL (n=276,283) 10.9  (1.21) 10.7  (1.14)
Diarrhoea: Week 4 (n=234,246) 9.1  (1.25) 12.2  (1.30)
Diarrhoea: Week 7 (n=180,220) 8.7  (1.40) 14.2  (1.65)
Diarrhoea: Week 10 (n=174,202) 10.5  (1.51) 11.9  (1.55)
Diarrhoea: Week 13 (n=152,183) 6.6  (1.21) 12.0  (1.66)
Diarrhoea: Week 16 (n=120,165) 8.1  (1.63) 12.9  (1.61)
Diarrhoea: Week 19 (n=114,143) 7.3  (1.70) 10.3  (1.45)
Diarrhoea: Week 22 (n=78,143) 6.0  (1.80) 9.6  (1.43)
Diarrhoea: Week 25 (n=64,124) 7.3  (1.74) 6.2  (1.23)
Diarrhoea: Week 28 (n=47,111) 5.7  (1.85) 4.8  (1.20)
Diarrhoea: Week 31 (n=45,95) 5.9  (1.92) 4.9  (1.32)
Diarrhoea: Week 34 (n=37,87) 5.4  (2.05) 5.7  (1.56)
Diarrhoea: Week 37 (n=29,64) 5.7  (2.38) 4.2  (1.39)
Diarrhoea: Week 40 (n=24,55) 6.9  (2.82) 3.0  (1.79)
Diarrhoea: Week 43 (n=12,42) 8.3  (4.35) 2.4  (1.76)
Diarrhoea: Week 46 (n=14,42) 4.8  (3.24) 1.6  (1.11)
Diarrhoea: Week 49 (n=10,36) 10.0  (5.09) 3.7  (1.77)
Diarrhoea: Week 52 (n=8,29) 8.3  (5.46) 2.3  (1.60)
Diarrhoea: Week 55 (n=6,24) 11.1  (7.03) 4.2  (2.30)
Diarrhoea: Week 58 (n=6,21) 11.1  (7.03) 4.8  (2.61)
Diarrhoea: Week 61 (n=4,17) 16.7  (9.62) 0.0  (0.00)
Diarrhoea: Week 64 (n=3,20) 11.1  (11.11) 3.3  (2.29)
Diarrhoea: Week 67 (n=4,17) 16.7  (9.62) 2.0  (1.96)
Diarrhoea: Week 70 (n=3,14) 11.1  (11.11) 3.3  (2.29)
Diarrhoea: Week 73 (n=3,12) 11.1  (11.11) 2.0  (1.96)
Diarrhoea: Week 76 (n=3,8) 22.2  (11.11) 0.0  (0.00)
Diarrhoea: Week 79 (n=3,9) 11.1  (11.11) 0.0  (0.00)
Diarrhoea: Week 82 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Diarrhoea: Week 85 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Diarrhoea: Week 88 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Diarrhoea: Week 91 (n=2,4) 16.7  (16.67) 0.0  (0.00)
Diarrhoea: Week 94 (n=2,6) 16.7  (16.67) 0.0  (0.00)
Diarrhoea: Week 97 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 112 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Diarrhoea: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 118 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 124 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Diarrhoea: Week 127 (n=1,3) 0.0  (0) 0.0  (0.00)
Diarrhoea: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Diarrhoea: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Diarrhoea: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Diarrhoea: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Diarrhoea: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Diarrhoea: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Diarrhoea: Final Visit (n=157,160) 10.0  (1.55) 10.0  (1.67)
Financial Difficulties: BL (n=274,286) 27.3  (1.91) 29.3  (1.89)
Financial Difficulties: Week 4 (n=234,249) 23.6  (1.93) 27.7  (1.99)
Financial Difficulties: Week 7 (n=178,220) 23.6  (2.08) 23.9  (1.96)
Financial Difficulties: Week 10 (n=175,202) 21.5  (2.11) 23.3  (2.03)
Financial Difficulties: Week 13 (n=151,181) 22.5  (2.23) 22.7  (2.08)
Financial Difficulties: Week 16 (n=120,165) 23.1  (2.58) 24.4  (2.26)
Financial Difficulties: Week 19 (n=113,143) 20.6  (2.53) 22.4  (2.49)
Financial Difficulties: Week 22 (n=78,142) 19.7  (3.01) 24.9  (2.52)
Financial Difficulties: Week 25 (n=63,124) 16.4  (3.01) 22.3  (2.34)
Financial Difficulties: Week 28 (n=45,111) 17.0  (3.76) 21.6  (2.55)
Financial Difficulties: Week 31 (n=45,94) 15.6  (3.76) 23.4  (2.89)
Financial Difficulties: Week 34 (n=36,87) 10.2  (2.92) 24.5  (2.96)
Financial Difficulties: Week 37 (n=29,64) 13.8  (4.83) 23.4  (3.38)
Financial Difficulties: Week 40 (n=24,55) 22.2  (5.18) 23.6  (3.74)
Financial Difficulties: Week 43 (n=12,43) 16.7  (7.68) 19.4  (3.72)
Financial Difficulties: Week 46 (n=14,42) 16.7  (5.79) 18.3  (3.45)
Financial Difficulties: Week 49 (n=10,35) 16.7  (5.56) 20.0  (4.14)
Financial Difficulties: Week 52 (n=8,29) 8.3  (5.46) 20.7  (4.50)
Financial Difficulties: Week 55 (n=6,24) 16.7  (11.39) 18.1  (5.30)
Financial Difficulties: Week 58 (n=6,21) 11.1  (7.03) 22.2  (6.23)
Financial Difficulties: Week 61 (n=4,17) 16.7  (9.62) 23.5  (6.86)
Financial Difficulties: Week 64 (n=3,20) 11.1  (11.11) 16.7  (4.52)
Financial Difficulties: Week 67 (n=4,17) 16.7  (9.62) 17.6  (5.05)
Financial Difficulties: Week 70 (n=3,14) 11.1  (11.11) 19.0  (5.76)
Financial Difficulties: Week 73 (n=3,12) 11.1  (11.11) 19.4  (4.95)
Financial Difficulties: Week 76 (n=3,8) 11.1  (11.11) 25.0  (8.33)
Financial Difficulties: Week 79 (n=3,9) 11.1  (11.11) 25.9  (10.80)
Financial Difficulties: Week 82 (n=2,6) 16.7  (16.67) 22.2  (7.03)
Financial Difficulties: Week 85 (n=2,6) 16.7  (16.67) 16.7  (7.45)
Financial Difficulties: Week 88 (n=2,6) 16.7  (16.67) 16.7  (7.45)
Financial Difficulties: Week 91 (n=2,4) 16.7  (16.67) 25.0  (8.33)
Financial Difficulties: Week 94 (n=2,6) 16.7  (16.67) 16.7  (7.45)
Financial Difficulties: Week 97 (n=1,5) 0.0 [1]   (NA) 20.0  (8.16)
Financial Difficulties: Week 100 (n=1,4) 0.0 [1]   (NA) 16.7  (9.62)
Financial Difficulties: Week 103 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Financial Difficulties: Week 106 (n=1,4) 0.0 [1]   (NA) 16.7  (9.62)
Financial Difficulties: Week 109 (n=1,4) 0.0 [1]   (NA) 16.7  (9.62)
Financial Difficulties: Week 112 (n=1,5) 0.0 [1]   (NA) 13.3  (8.16)
Financial Difficulties: Week 115 (n=1,4) 0.0 [1]   (NA) 16.7  (9.62)
Financial Difficulties: Week 118 (n=1,5) 0.0 [1]   (NA) 13.3  (8.16)
Financial Difficulties: Week 121 (n=1,5) 0.0 [1]   (NA) 13.3  (8.16)
Financial Difficulties: Week 124 (n=1,5) 0.0 [1]   (NA) 13.3  (8.16)
Financial Difficulties: Week 127 (n=1,3) 0.0 [1]   (NA) 11.1  (11.11)
Financial Difficulties: Week 130 (n=0,3) NA [2]   (NA) 11.1  (11.11)
Financial Difficulties: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Financial Difficulties: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Financial Difficulties: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Financial Difficulties: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Financial Difficulties: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Financial Difficulties: Final Visit (n=158,160) 26.6  (2.39) 27.9  (2.51)
[1]
Only 1 participant was analyzed in this treatment group at this timepoint, therefore standard error of the mean could not be calculated.
[2]
No participants were analyzed in this treatment group at this timepoint.
12.Secondary Outcome
Title EORTC Quality of Life Questionnaire-Stomach Cancer Specific (QLQ STO22) Questionnaire Scores
Hide Description The QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.
Time Frame BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; n = number of participants assessed for a specific parameter at a given visit.
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Mean (Standard Error)
Unit of Measure: scores on a scale
Dysphagia Scale: BL (n=276,287) 18.7  (1.27) 16.6  (1.21)
Dysphagia Scale: Week 4 (n=234,250) 11.8  (0.92) 12.5  (1.01)
Dysphagia Scale: Week 7 (n=181,220) 10.9  (1.16) 12.8  (1.22)
Dysphagia Scale: Week 10 (n=176,203) 8.5  (0.97) 10.6  (1.19)
Dysphagia Scale: Week 13 (n=152,183) 8.8  (1.15) 9.0  (1.09)
Dysphagia Scale: Week 16 (n=120,165) 10.2  (1.50) 9.1  (1.09)
Dysphagia Scale: Week 19 (n=114,143) 9.5  (1.52) 8.8  (1.26)
Dysphagia Scale: Week 22 (n=79,143) 10.0  (2.11) 7.8  (1.19)
Dysphagia Scale: Week 25 (n=64,124) 6.9  (1.99) 6.8  (1.27)
Dysphagia Scale: Week 28 (n=47,111) 6.6  (1.84) 5.3  (1.03)
Dysphagia Scale: Week 31 (n=45,95) 6.4  (2.16) 6.8  (1.40)
Dysphagia Scale: Week 34 (n=37,87) 3.9  (1.44) 7.5  (1.51)
Dysphagia Scale: Week 37 (n=29,64) 5.4  (2.04) 7.3  (2.03)
Dysphagia Scale: Week 40 (n=24,55) 3.7  (1.59) 6.5  (1.82)
Dysphagia Scale: Week 43 (n=12,43) 4.6  (2.89) 5.2  (1.63)
Dysphagia Scale: Week 46 (n=14,42) 2.4  (1.26) 2.9  (1.08)
Dysphagia Scale: Week 49 (n=10,36) 4.4  (2.46) 2.2  (0.74)
Dysphagia Scale: Week 52 (n=8,30) 1.4  (1.39) 4.4  (1.81)
Dysphagia Scale: Week 55 (n=6,24) 0.0  (0.00) 3.7  (1.28)
Dysphagia Scale: Week 58 (n=6,21) 3.7  (2.34) 3.2  (1.56)
Dysphagia Scale: Week 61 (n=4,17) 2.8  (2.78) 0.7  (0.65)
Dysphagia Scale: Week 64 (n=3,20) 0.0  (0.00) 3.3  (1.99)
Dysphagia Scale: Week 67 (n=4,16) 2.8  (2.78) 2.8  (2.15)
Dysphagia Scale: Week 70 (n=3,14) 0.0  (0.00) 3.2  (2.45)
Dysphagia Scale: Week 73 (n=3,12) 0.0  (0.00) 4.6  (2.54)
Dysphagia Scale: Week 76 (n=3,8) 0.0  (0.00) 2.8  (1.82)
Dysphagia Scale: Week 79 (n=3,9) 0.0  (0.00) 2.5  (1.63)
Dysphagia Scale: Week 82 (n=2,6) 0.0  (0.00) 3.7  (2.34)
Dysphagia Scale: Week 85 (n=2,6) 0.0  (0.00) 1.9  (1.85)
Dysphagia Scale: Week 88 (n=2,6) 0.0  (0.00) 1.9  (1.85)
Dysphagia Scale: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Dysphagia Scale: Week 94 (n=2,6) 0.0  (0.00) 1.9  (1.85)
Dysphagia Scale: Week 97 (n=1,5) 0.0 [1]   (NA) 2.2  (2.22)
Dysphagia Scale: Week 100 (n=1,4) 0.0 [1]   (NA) 2.8  (2.78)
Dysphagia Scale: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 112 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 118 (n=1,5) 0.0 [1]   (NA) 2.2  (2.22)
Dysphagia Scale: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Dysphagia Scale: Week 139 (n=0,2) NA [2]   (NA) 5.6  (5.56)
Dysphagia Scale: Week 142 (n=0,2) NA [2]   (NA) 5.6  (5.56)
Dysphagia Scale: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Dysphagia Scale: Final Visit (n=157,159 15.4  (1.77) 17.0  (1.92)
Pain Scale: BL (n=276,287) 29.7  (1.32) 27.0  (1.20)
Pain Scale: Week 4 (n=234,250) 21.6  (1.15) 21.8  (1.05)
Pain Scale: Week 7 (n=181,219) 19.4  (1.26) 20.1  (1.30)
Pain Scale: Week 10 (n=176,203) 17.0  (1.11) 17.5  (1.14)
Pain Scale: Week 13 (n=152,183) 16.0  (1.25) 16.2  (1.21)
Pain Scale: Week 16 (n=120,165) 17.0  (1.45) 15.9  (1.23)
Pain Scale: Week 19 (n=114,143) 19.2  (1.95) 16.3  (1.32)
Pain Scale: Week 22 (n=79,143) 15.8  (2.05) 15.1  (1.58)
Pain Scale: Week 25 (n=64,124) 11.3  (1.82) 14.4  (1.63)
Pain Scale: Week 28 (n=47,111) 11.2  (1.95) 14.0  (1.64)
Pain Scale: Week 31 (n=45,95) 12.6  (2.33) 14.6  (2.09)
Pain Scale: Week 34 (n=37,87) 12.2  (2.18) 12.5  (2.04)
Pain Scale: Week 37 (n=29,64) 13.8  (2.90) 13.8  (2.63)
Pain Scale: Week 40 (n=24,55) 14.9  (2.97) 11.8  (2.28)
Pain Scale: Week 43 (n=12,43) 13.0  (3.41) 9.7  (1.98)
Pain Scale: Week 46 (n=14,42) 15.5  (3.13) 10.1  (2.35)
Pain Scale: Week 49 (n=10,36) 11.7  (4.51) 9.5  (1.79)
Pain Scale: Week 52 (n=8,30) 9.4  (4.00) 8.6  (2.69)
Pain Scale: Week 55 (n=6,24) 9.7  (5.01) 4.5  (1.42)
Pain Scale: Week 58 (n=6,21) 5.6  (4.12) 6.3  (1.90)
Pain Scale: Week 61 (n=4,17) 4.2  (2.41) 5.4  (2.36)
Pain Scale: Week 64 (n=3,20) 2.8  (2.78) 9.6  (2.28)
Pain Scale: Week 67 (n=4,16) 4.2  (4.17) 8.3  (2.95)
Pain Scale: Week 70 (n=3,14) 2.8  (2.78) 6.5  (2.17)
Pain Scale: Week 73 (n=3,12) 0.0  (0.00) 9.7  (3.95)
Pain Scale: Week 76 (n=3,8) 5.6  (5.56) 5.2  (2.19)
Pain Scale: Week 79 (n=3,9) 2.8  (2.78) 7.4  (3.79)
Pain Scale: Week 82 (n=2,6) 0.0  (0.00) 6.9  (3.98)
Pain Scale: Week 85 (n=2,6) 4.2  (4.17) 5.6  (4.12)
Pain Scale: Week 88 (n=2,6) 8.3  (8.33) 5.6  (2.78)
Pain Scale: Week 91 (n=2,6) 0.0  (0.00) 2.1  (2.08)
Pain Scale: Week 94 (n=2,6) 0.0  (0.00) 5.6  (3.51)
Pain Scale: Week 97 (n=1,5) 0.0 [1]   (NA) 8.3  (3.73)
Pain Scale: Week 100 (n=1,4) 0.0 [1]   (NA) 6.3  (2.08)
Pain Scale: Week 103 (n=1,4) 0.0 [1]   (NA) 8.3  (3.40)
Pain Scale: Week 106 (n=1,4) 0.0 [1]   (NA) 6.3  (3.99)
Pain Scale: Week 109 (n=1,4) 0.0 [1]   (NA) 4.2  (2.41)
Pain Scale: Week 112 (n=1,5) 0.0 [1]   (NA) 10.0  (4.86)
Pain Scale: Week 115 (n=1,4) 0.0 [1]   (NA) 4.2  (2.41)
Pain Scale: Week 118 (n=1,5) 0.0 [1]   (NA) 8.3  (3.73)
Pain Scale: Week 121 (n=1,5) 0.0 [1]   (NA) 10.0  (4.86)
Pain Scale: Week 124 (n=1,5) 0.0 [1]   (NA) 8.3  (3.73)
Pain Scale: Week 127 (n=1,3) 0.0 [1]   (NA) 8.3  (8.33)
Pain Scale: Week 130 (n=0,3) NA [2]   (NA) 11.1  (7.35)
Pain Scale: Week 133 (n=1,3) 0.0 [1]   (NA) 13.9  (7.35)
Pain Scale: Week 136 (n=0,2) NA [2]   (NA) 12.5  (4.17)
Pain Scale: Week 139 (n=0,2) NA [2]   (NA) 8.3  (8.33)
Pain Scale: Week 142 (n=0,2) NA [2]   (NA) 8.3  (0.00)
Pain Scale: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Pain Scale: Final Visit (n=157,160) 24.7  (1.60) 26.8  (2.02)
Reflux Symptoms Scale: BL (n=275,287) 18.3  (1.29) 16.9  (1.12)
Reflux Symptoms Scale: Week 4 (n=234,250) 14.8  (1.14) 16.0  (1.09)
Reflux Symptoms Scale: Week 7 (n=180,220) 12.8  (1.26) 15.4  (1.20)
Reflux Symptoms Scale: Week 10 (n=176,203) 12.6  (1.29) 13.5  (1.18)
Reflux Symptoms Scale: Week 13 (n=152,182) 12.8  (1.39) 12.9  (1.34)
Reflux Symptoms Scale: Week 16 (n=120,165) 12.0  (1.55) 14.4  (1.58)
Reflux Symptoms Scale: Week 19 (n=114,165) 11.3  (1.76) 10.6  (1.24)
Reflux Symptoms Scale: Week 22 (n=79,143) 9.0  (1.79) 10.6  (1.37)
Reflux Symptoms Scale: Week 25 (n=64,124) 5.6  (1.21) 9.7  (1.34)
Reflux Symptoms Scale: Week 28 (n=47,111) 6.6  (1.61) 9.6  (1.42)
Reflux Symptoms Scale: Week 31 (n=45,95) 7.4  (1.69) 10.1  (1.93)
Reflux Symptoms Scale: Week 34 (n=45,95) 7.2  (2.16) 9.3  (1.77)
Reflux Symptoms Scale: Week 37 (n=29,64) 6.1  (1.62) 10.9  (2.38)
Reflux Symptoms Scale: Week 40 (n=24,55) 7.9  (2.80) 9.3  (2.13)
Reflux Symptoms Scale: Week 43 (n=12,42) 7.4  (3.44) 9.0  (2.07)
Reflux Symptoms Scale: Week 46 (n=14,42) 4.8  (1.53) 6.6  (1.97)
Reflux Symptoms Scale: Week 49 (n=10,36) 2.2  (1.48) 6.5  (1.43)
Reflux Symptoms Scale: Week 52 (n=8,30) 2.8  (1.82) 8.1  (2.55)
Reflux Symptoms Scale: Week 55 (n=6,24) 5.6  (5.56) 6.5  (2.00)
Reflux Symptoms Scale: Week 58 (n=6,21) 0.0  (0.00) 5.3  (1.65)
Reflux Symptoms Scale: Week 61 (n=4,17) 2.8  (2.78) 2.6  (1.52)
Reflux Symptoms Scale: Week 64 (n=3,20) 3.7  (3.70) 3.9  (1.85)
Reflux Symptoms Scale: Week 67 (n=4,16) 2.8  (2.78) 6.3  (2.48)
Reflux Symptoms Scale: Week 70 (n=3,13) 3.7  (3.70) 4.3  (2.00)
Reflux Symptoms Scale: Week 73 (n=3,12) 0.0  (0.00) 7.9  (2.60)
Reflux Symptoms Scale: Week 76 (n=3,8) 3.7  (3.70) 1.4  (1.39)
Reflux Symptoms Scale: Week 79 (n=3,9) 0.0  (0.00) 3.7  (2.62)
Reflux Symptoms Scale: Week 82 (n=2,6) 0.0  (0.00) 5.6  (2.48)
Reflux Symptoms Scale: Week 85 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Reflux Symptoms Scale: Week 88 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Reflux Symptoms Scale: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Reflux Symptoms Scale: Week 94 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Reflux Symptoms Scale: Week 97 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 106 (n=1,4) 0.0 [1]   (NA) 2.8  (2.78)
Reflux Symptoms Scale: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 112 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 118 (n=1,5) 0.0 [1]   (NA) 4.4  (4.44)
Reflux Symptoms Scale: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 124 (n=1,5) 0.0 [1]   (NA) 6.7  (4.44)
Reflux Symptoms Scale: Week 127 (n=1,3) 0.0 [1]   (NA) 7.4  (7.41)
Reflux Symptoms Scale: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Reflux Symptoms Scale: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Reflux Symptoms Scale: Final Visit (n=1,5) 15.3  (1.48) 18.3  (1.72)
Eating Restrictions (ER) Scale: BL (n=276,287) 27.4  (1.44) 23.9  (1.30)
ER Scale: Week 4 (n=234,250) 20.6  (1.24) 21.1  (1.19)
ER Scale: Week 7 (n=181,220) 18.8  (1.36) 19.0  (1.26)
ER Scale: Week 10 (n=176,203) 17.5  (1.25) 17.4  (1.23)
ER Scale: Week 13 (n=152,183) 16.0  (1.77) 17.0  (1.34)
ER Scale: Week 16 (n=120,165) 17.8  (1.77) 15.1  (1.40)
ER Scale: Week 19 (n=114,143) 20.8  (2.01) 15.5  (1.53)
ER Scale: Week 22 (n=79,143) 15.5  (2.14) 13.6  (1.56)
ER Scale: Week 25 (n=64,124) 11.6  (2.14) 12.9  (1.39)
ER Scale: Week 28 (n=47,111) 13.9  (2.64) 11.3  (1.37)
ER Scale: Week 31 (n=45,95) 13.4  (2.69) 12.5  (2.03)
ER Scale: Week 34 (n=37,87) 10.6  (2.16) 10.9  (1.90)
ER Scale: Week 37 (n=29,64) 12.5  (3.10) 9.5  (2.11)
ER Scale: Week 40 (n=24,55) 13.5  (3.32) 9.5  (2.21)
ER Scale: Week 43 (n=12,43) 9.7  (3.22) 7.0  (1.88)
ER Scale: Week 46 (n=14,42) 10.9  (3.07) 6.0  (1.31)
ER Scale: Week 49 (n=10,36) 11.7  (3.09) 8.1  (1.83)
ER Scale: Week 52 (n=8,30) 5.2  (2.19) 9.3  (2.31)
ER Scale: Week 55 (n=6,24) 8.3  (4.30) 5.2  (1.86)
ER Scale: Week 58 (n=6,21) 9.7  (5.45) 6.0  (2.31)
ER Scale: Week 61 (n=4,17) 4.2  (2.41) 5.4  (2.01)
ER Scale: Week 64 (n=3,20) 0.0  (0.00) 8.3  (2.42)
ER Scale: Week 67 (n=4,16) 8.3  (4.81) 10.4  (3.36)
ER Scale: Week 70 (n=3,14) 2.8  (2.78) 6.5  (2.34)
ER Scale: Week 73 (n=3,12) 5.6  (5.56) 9.0  (3.32)
ER Scale: Week 76 (n=3,8) 2.8  (2.78) 5.2  (3.50)
ER Scale: Week 79 (n=3,9) 5.6  (5.56) 5.6  (3.11)
ER Scale: Week 82 (n=2,6) 4.2  (4.17) 2.8  (2.78)
ER Scale: Week 85 (n=2,6) 4.2  (4.17) 4.2  (2.85)
ER Scale: Week 88 (n=2,6) 4.2  (4.17) 4.2  (1.86)
ER Scale: Week 91 (n=2,4) 8.3  (8.33) 4.2  (4.17)
ER Scale: Week 94 (n=2,6) 0.0  (0.00) 4.2  (2.85)
ER Scale: Week 97 (n=1,5) 0.0 [1]   (NA) 6.7  (3.12)
ER Scale: Week 100 (n=1,4) 0.0 [1]   (NA) 6.3  (3.99)
ER Scale: Week 103 (n=1,4) 0.0 [1]   (NA) 6.3  (3.99)
ER Scale: Week 106 (n=1,4) 0.0 [1]   (NA) 4.2  (4.17)
ER Scale: Week 109 (n=1,4) 0.0 [1]   (NA) 4.2  (4.17)
ER Scale: Week 112 (n=1,5) 0.0 [1]   (NA) 3.3  (3.33)
ER Scale: Week 115 (n=1,4) 0.0 [1]   (NA) 4.2  (4.17)
ER Scale: Week 118 (n=1,5) 0.0 [1]   (NA) 6.7  (3.12)
ER Scale: Week 121 (n=1,5) 0.0 [1]   (NA) 5.0  (3.33)
ER Scale: Week 124 (n=1,5) 0.0 [1]   (NA) 1.7  (1.67)
ER Scale: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
ER Scale: Week 130 (n=0,3) NA [2]   (NA) 8.3  (4.81)
ER Scale: Week 133 (n=1,3) 0.0 [1]   (NA) 5.6  (2.78)
ER Scale: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
ER Scale: Week 139 (n=0,2) NA [2]   (NA) 4.2  (4.17)
ER Scale: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
ER Scale: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
ER Scale: Final Visit (n=157,160) 23.8  (1.85) 22.8  (1.84)
Anxiety Scale: BL (n=276,287) 47.5  (1.66) 48.2  (1.54)
Anxiety Scale: Week 4 (n=234,250) 42.0  (1.66) 43.8  (1.60)
Anxiety Scale: Week 7 (n=181,220) 40.6  (1.77) 39.3  (1.66)
Anxiety Scale: Week 10 (n=176,203) 38.2  (1.98) 38.2  (1.70)
Anxiety Scale: Week 13 (n=152,183) 35.7  (2.01) 37.5  (1.99)
Anxiety Scale: Week 16 (n=120,165) 32.9  (2.27) 37.1  (2.10)
Anxiety Scale: Week 19 (n=114,143) 35.8  (2.40) 34.9  (2.04)
Anxiety Scale: Week 22 (n=79,143) 31.7  (3.16) 32.8  (2.05)
Anxiety Scale: Week 25 (n=64,124) 25.2  (2.86) 29.2  (2.03)
Anxiety Scale: Week 28 (n=47,111) 27.4  (3.65) 26.9  (1.88)
Anxiety Scale: Week 31 (n=45,95) 29.1  (4.36) 28.4  (2.32)
Anxiety Scale: Week 34 (n=37,87) 23.1  (3.69) 27.8  (2.33)
Anxiety Scale: Week 37 (n=29,64) 27.2  (4.79) 28.2  (2.87)
Anxiety Scale: Week 40 (n=24,55) 29.6  (3.99) 26.3  (2.77)
Anxiety Scale: Week 43 (n=12,43) 30.6  (7.63) 25.1  (2.91)
Anxiety Scale: Week 46 (n=14,42) 26.2  (6.34) 23.3  (3.00)
Anxiety Scale: Week 49 (n=14,42) 20.0  (7.55) 25.9  (3.03)
Anxiety Scale: Week 52 (n=8,30) 23.6  (7.98) 27.4  (4.15)
Anxiety Scale: Week 55 (n=6,24) 31.5  (12.31) 28.2  (3.90)
Anxiety Scale: Week 58 (n=6,21) 20.4  (10.11) 21.7  (3.38)
Anxiety Scale: Week 61 (n=4,17) 8.3  (5.32) 25.5  (5.37)
Anxiety Scale: Week 64 (n=3,20) 5.6  (5.56) 23.9  (4.21)
Anxiety Scale: Week 67 (n=4,16) 11.1  (6.42) 18.8  (3.47)
Anxiety Scale: Week 70 (n=3,14) 3.7  (3.70) 27.0  (5.91)
Anxiety Scale: Week 73 (n=3,12) 7.4  (7.41) 28.7  (6.03)
Anxiety Scale: Week 76 (n=3,8) 0.0  (0.00) 27.8  (8.13)
Anxiety Scale: Week 79 (n=3,9) 11.1  (11.11) 33.3  (8.28)
Anxiety Scale: Week 82 (n=2,6) 11.1  (11.11) 25.9  (8.92)
Anxiety Scale: Week 85 (n=2,6) 11.1  (11.11) 24.1  (3.41)
Anxiety Scale: Week 88 (n=2,6) 11.1  (11.11) 14.8  (5.49)
Anxiety Scale: Week 91 (n=2,4) 11.1  (11.11) 22.2  (4.54)
Anxiety Scale: Week 94 (n=2,6) 5.6  (5.56) 22.2  (2.87)
Anxiety Scale: Week 97 (n=1,5) 0.0 [1]   (NA) 31.1  (5.44)
Anxiety Scale: Week 100 (n=1,4) 0.0 [1]   (NA) 16.7  (5.56)
Anxiety Scale: Week 103 (n=1,4) 0.0 [1]   (NA) 22.2  (4.54)
Anxiety Scale: Week 106 (n=1,4) 0.0 [1]   (NA) 19.4  (5.32)
Anxiety Scale: Week 109 (n=1,4) 0.0 [1]   (NA) 16.7  (7.17)
Anxiety Scale: Week 112 (n=1,5) 0.0 [1]   (NA) 22.2  (4.97)
Anxiety Scale: Week 115 (n=1,4) 0.0 [1]   (NA) 19.4  (8.33)
Anxiety Scale: Week 118 (n=1,5) 0.0 [1]   (NA) 20.0  (6.48)
Anxiety Scale: Week 121 (n=1,5) 0.0 [1]   (NA) 15.6  (7.54)
Anxiety Scale: Week 124 (n=1,5) 0.0 [1]   (NA) 17.8  (5.67)
Anxiety Scale: Week 127 (n=1,3) 0.0 [1]   (NA) 22.2  (11.11)
Anxiety Scale: Week 130 (n=0,3) NA [2]   (NA) 18.5  (9.80)
Anxiety Scale: Week 133 (n=1,3) 0.0 [1]   (NA) 18.5  (9.80)
Anxiety Scale: Week 136 (n=0,2) NA [2]   (NA) 16.7  (16.67)
Anxiety Scale: Week 139 (n=0,2) NA [2]   (NA) 11.1  (11.11)
Anxiety Scale: Week 142 (n=0,2) NA [2]   (NA) 16.7  (16.67)
Anxiety Scale: Week 145 (n=0,2) NA [2]   (NA) 0.0 [1]   (NA)
Anxiety Scale: Final Visit (n=157,160) 41.5  (2.19) 40.9  (2.22)
Dry Mouth: BL (n=274,287) 24.5  (1.70) 23.9  (1.70)
Dry Mouth: Week 4 (n=232,249) 24.0  (1.81) 23.3  (1.59)
Dry Mouth: Week 7 (n=180,219) 24.6  (2.02) 26.9  (1.87)
Dry Mouth: Week 10 (n=176,203) 23.5  (1.85) 25.0  (1.96)
Dry Mouth: Week 13 (n=152,183) 23.2  (2.06) 21.1  (1.95)
Dry Mouth: Week 16 (n=120,165) 23.9  (2.41) 23.4  (2.19)
Dry Mouth: Week 19 (n=113,143) 22.4  (2.56) 20.5  (2.17)
Dry Mouth: Week 22 (n=79,143) 19.0  (2.92) 16.3  (2.06)
Dry Mouth: Week 25 (n=64,124) 16.1  (3.06) 12.1  (1.80)
Dry Mouth: Week 28 (n=47,111) 10.6  (2.51) 10.8  (1.55)
Dry Mouth: Week 31 (n=45,95) 12.6  (3.23) 11.2  (2.21)
Dry Mouth: Week 34 (n=37,87) 9.9  (3.38) 9.6  (1.88)
Dry Mouth: Week 37 (n=29,64) 12.6  (4.19) 9.4  (2.28)
Dry Mouth: Week 40 (n=23,55) 8.7  (3.76) 7.3  (2.40)
Dry Mouth: Week 43 (n=12,43) 11.1  (4.74) 6.2  (2.00)
Dry Mouth: Week 46 (n=14,42) 9.5  (4.18) 4.8  (1.82)
Dry Mouth: Week 49 (n=10,36) 16.7  (5.56) 6.5  (2.23)
Dry Mouth: Week 52 (n=8,30) 12.5  (6.10) 10.0  (3.26)
Dry Mouth: Week 55 (n=6,24) 5.6  (5.56) 8.3  (3.01)
Dry Mouth: Week 58 (n=6,21) 11.1  (7.03) 14.3  (4.35)
Dry Mouth: Week 61 (n=4,17) 8.3  (8.33) 11.8  (4.90)
Dry Mouth: Week 64 (n=3,20) 0.0  (0.00) 6.7  (3.06)
Dry Mouth: Week 67 (n=4,16) 8.3  (8.33) 8.3  (4.81)
Dry Mouth: Week 70 (n=3,14) 0.0  (0.00) 11.9  (5.64)
Dry Mouth: Week 73 (n=3,12) 0.0  (0.00) 13.9  (4.95)
Dry Mouth: Week 76 (n=3,8) 0.0  (0.00) 20.8  (8.77)
Dry Mouth: Week 79 (n=3,9) 0.0  (0.00) 11.1  (5.56)
Dry Mouth: Week 82 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Dry Mouth: Week 85 (n=2,6) 16.7  (16.67) 0.0  (0.00)
Dry Mouth: Week 88 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Dry Mouth: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Dry Mouth: Week 94 (n=2,6) 0.0  (0.00) 0.0  (0.00)
Dry Mouth: Week 97 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.0)
Dry Mouth: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 112 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 118 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Dry Mouth: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Dry Mouth: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Dry Mouth: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Dry Mouth: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Dry Mouth: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Dry Mouth: Final Visit (n=157,157) 24.0  (2.52) 23.6  (2.43)
Taste: BL (n=275,286) 17.2  (1.56) 17.9  (1.64)
Taste: Week 4 (n=234,249) 20.7  (1.63) 24.8  (1.79)
Taste: Week 7 (n=179,217) 20.1  (1.78) 24.0  (1.85)
Taste: Week 10 (n=176,200) 21.8  (1.86) 25.3  (2.01)
Taste: Week 13 (n=151,181) 19.9  (2.08) 25.2  (2.20)
Taste: Week 16 (n=119,165) 20.4  (2.22) 23.8  (2.23)
Taste: Week 19 (n=113,143) 24.5  (2.37) 22.6  (2.26)
Taste: Week 22 (n=79,143) 19.0  (2.86) 19.6  (2.15)
Taste: Week 25 (n=64,124) 10.9  (2.23) 15.9  (1.96)
Taste: Week 28 (n=47,111) 12.1  (2.76) 14.7  (2.03)
Taste: Week 31 (n=45,95) 8.1  (2.63) 13.0  (2.65)
Taste: Week 34 (n=37,87) 6.3  (2.53) 9.6  (2.10)
Taste: Week 37 (n=28,64) 8.3  (3.26) 7.8  (2.20)
Taste: Week 40 (n=24,55) 8.3  (3.01) 7.9  (2.73)
Taste: Week 43 (n=12,43) 5.6  (3.75) 7.0  (2.09)
Taste: Week 46 (n=14,42) 4.8  (3.24) 7.9  (2.74)
Taste: Week 49 (n=9,36) 7.4  (4.90) 4.6  (1.95)
Taste: Week 52 (n=8,30) 4.2  (4.17) 7.8  (3.46)
Taste: Week 55 (n=6,24) 11.1  (7.03) 4.2  (2.30)
Taste: Week 58 (n=6,21) 11.1  (7.03) 4.8  (2.61)
Taste: Week 61 (n=4,17) 8.3  (8.33) 0.0  (0.00)
Taste: Week 64 (n=3,20) 11.1  (11.11) 1.7  (1.67)
Taste: Week 67 (n=4,16) 8.3  (8.33) 4.2  (2.85)
Taste: Week 70 (n=3,14) 0.0  (0.00) 0.0  (0.00)
Taste: Week 73 (n=3,12) 0.0  (0.00) 2.8  (2.78)
Taste: Week 76 (n=3,8) 0.0  (0.00) 0.0  (0.00)
Taste: Week 79 (n=3,9) 0.0  (0.00) 0.0  (0.00)
Taste: Week 82 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Taste: Week 85 (n=2, 6) 0.0  (0.00) 0.0  (0.00)
Taste: Week 88 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Taste: Week 91 (n=2,4) 0.0  (0.00) 0.0  (0.00)
Taste: Week 94 (n=2,6) 0.0  (0.00) 5.6  (5.56)
Taste: Week 97 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Taste: Week 100 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 103 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 106 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 109 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 112 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 115 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 118 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 121 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 124 (n=1,5) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 127 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Taste: Week 133 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Taste: Week 136 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Taste: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Taste: Week 142 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Taste: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Taste: Final Visit (n=157,158) 25.3  (2.26) 20.3  (2.28)
Body Image: BL (n=272,286) 30.9  (1.95) 31.9  (1.93)
Body Image: Week 4 (n=233,249) 32.6  (2.10) 31.7  (2.03)
Body Image: Week 7 (n=180,219) 30.7  (2.19) 27.9  (1.94)
Body Image: Week 10 (n=175,203) 30.1  (2.27) 28.4  (2.05)
Body Image: Week 13 (n=152,182) 28.9  (2.54) 28.2  (2.36)
Body Image: Week 16 (n=119,165) 29.1  (2.69) 28.1  (2.29)
Body Image: Week 19 (n=114,140) 30.7  (2.82) 25.0  (2.53)
Body Image: Week 22 (n=79,143) 28.7  (3.59) 22.4  (2.29)
Body Image: Week 25 (n=64,124) 22.4  (3.32) 22.6  (2.60)
Body Image: Week 28 (n=47,111) 23.4  (4.41) 20.1  (2.53)
Body Image: Week 31 (n=45,95) 25.2  (4.87) 19.3  (2.80)
Body Image: Week 34 (n=37,87) 18.9  (4.75) 18.0  (2.66)
Body Image: Week 37 (n=29,64) 23.0  (5.99) 18.2  (3.48)
Body Image: Week 40 (n=24,55) 20.8  (5.96) 19.4  (3.53)
Body Image: Week 43 (n=12,43) 27.8  (6.91) 15.5  (3.90)
Body Image: Week 46 (n=14,42) 21.4  (6.64) 15.9  (3.81)
Body Image: Week 49 (n=10,36) 16.7  (7.45) 13.9  (4.07)
Body Image: Week 52 (n=8,30) 16.7  (8.91) 16.7  (3.83)
Body Image: Week 55 (n=6,24) 16.7  (11.39) 16.7  (4.91)
Body Image: Week 58 (n=6,21) 11.1  (7.03) 15.9  (5.45)
Body Image: Week 61 (n=4,17) 8.3  (8.33) 13.7  (5.76)
Body Image: Week 64 (n=3,20) 0.0  (0.00) 18.3  (4.51)
Body Image: Week 67 (n=4,16) 0.0  (0.00) 14.6  (4.27)
Body Image: Week 70 (n=4,14) 0.0  (0.00) 16.7  (5.79)
Body Image: Week 73 (n=3,12) 0.0  (0.00) 27.8  (9.02)
Body Image: Week 76 (n=3,8) 0.0  (0.00) 37.5  (11.68)
Body Image: Week 79 (n=3,9) 0.0  (0.00) 25.9  (9.26)
Body Image: Week 82 (n=2,6) 0.0  (0.00) 16.7  (7.45)
Body Image: Week 85 (n=2,6) 0.0  (0.00) 11.1  (7.03)
Body Image: Week 88 (n=2,5) 0.0  (0.00) 6.7  (6.67)
Body Image: Week 91 (n=2,4) 0.0  (0.00) 16.7  (9.62)
Body Image: Week 94 (n=2,6) 0.0  (0.00) 16.7  (7.45)
Body Image: Week 97 (n=1,5) 0.0 [1]   (NA) 13.3  (8.16)
Body Image: Week 100 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Body Image: Week 103 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Body Image: Week 106 (n=1,4) 0.0 [1]   (NA) 16.7  (9.62)
Body Image: Week 109 (n=1,4) 0.0 [1]   (NA) 8.3  (8.33)
Body Image: Week 112 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Body Image: Week 115 (n=1,4) 0.0 [1]   (NA) 16.7  (9.62)
Body Image: Week 118 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Body Image: Week 121 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Body Image: Week 124 (n=1,5) 0.0 [1]   (NA) 6.67  (6.67)
Body Image: Week 127 (n=1,3) 0.0 [1]   (NA) 11.1  (11.11)
Body Image: Week 130 (n=0,3) NA [2]   (NA) 0.0  (0.00)
Body Image: Week 133 (n=1,3) 0.0 [1]   (NA) 11.1  (11.11)
Body Image: Week 136 (n=0,2) NA [2]   (NA) 16.7  (16.67)
Body Image: Week 139 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Body Image: Week 142 (n=0,2) NA [2]   (NA) 16.7  (16.67)
Body Image: Week 145 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Body Image: Final Visit (n=157,159) 31.0  (2.58) 30.4  (2.42)
Hair Loss: BL (n=64,76) 15.1  (3.31) 25.0  (3.80)
Hair Loss: Week 4 (n=68,71) 20.1  (3.43) 16.4  (2.90)
Hair Loss: Week 7 (n=65,82) 25.1  (3.27) 19.1  (3.01)
Hair Loss: Week 10 (n=75,78) 21.8  (3.07) 20.1  (2.81)
Hair Loss: Week 13 (n=66,80) 22.2  (3.40) 20.4  (3.05)
Hair Loss: Week 16 (n=53,72) 28.3  (4.34) 23.6  (3.26)
Hair Loss: Week 19 (n=50,56) 23.3  (4.29) 21.4  (3.55)
Hair Loss: Week 22 (n=38,54) 20.2  (4.45) 22.2  (3.52)
Hair Loss: Week 25 (n=24,49) 13.9  (4.88) 18.4  (3.64)
Hair Loss: Week 28 (n=20,39) 26.7  (7.87) 14.5  (4.38)
Hair Loss: Week 31 (n=17,26) 15.7  (7.07) 10.3  (4.44)
Hair Loss: Week 34 (n=13,24) 7.7  (5.54) 16.7  (5.68)
Hair Loss: Week 37 (n=12,16) 8.3  (5.98) 12.5  (4.17)
Hair Loss: Week 40 (n=11,13) 12.1  (6.78) 12.8  (6.01)
Hair Loss: Week 43 (n=5,9) 6.7  (6.67) 3.7  (3.70)
Hair Loss: Week 46 (n=5,13) 26.7  (19.44) 5.1  (3.47)
Hair Loss: Week 49 (n=4,7) 0.0  (0.00) 9.5  (6.15)
Hair Loss: Week 52 (n=3,4) 11.1  (11.11) 8.3  (8.33)
Hair Loss: Week 55 (n=2,6) 16.7  (16.67) 0.0  (0.00)
Hair Loss: Week 58 (n=2,3) 16.7  (16.67) 0.0  (0.00)
Hair Loss: Week 61 (n=1,2) 0.0 [1]   (NA) 16.7  (16.67)
Hair Loss: Week 64 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 67 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 70 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 73 (n=1,5) 0.0 [1]   (NA) 6.7  (6.67)
Hair Loss: Week 76 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 79 (n=1,4) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 82 (n=1,1) 0.0 [1]   (NA) 0.0 [1]   (NA)
Hair Loss: Week 85 (n=1,1) 0.0 [1]   (NA) 0.0 [1]   (NA)
Hair Loss: Week 88 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 91 (n=1,1) 0.0 [1]   (NA) 0.0 [1]   (NA)
Hair Loss: Week 94 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 97 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 100 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 103 (n=1,1) 0.0 [1]   (NA) 0.0 [1]   (NA)
Hair Loss: Week 106 (n=1,1) 0.0 [1]   (NA) 0.0 [1]   (NA)
Hair Loss: Week 109 (n=0,2) NA [2]   (NA) 0.0  (0.00)
Hair Loss: Week 112 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 115 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 118 (n=1,3) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 121 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 124 (n=1,2) 0.0 [1]   (NA) 0.0  (0.00)
Hair Loss: Week 127 (n=1,1) 0.0 [1]   (NA) 0.0 [1]   (NA)
Hair Loss: Week 130 (n=0,1) NA [2]   (NA) 0.0 [1]   (NA)
Hair Loss: Week 133 (n=1,1) 0.0 [1]   (NA) 0.0 [1]   (NA)
Hair Loss: Final Visit (n=61,60) 23.0  (3.62) 19.4  (3.29)
[1]
Only 1 participant was analyzed in this treatment group at this timepoint, therefore standard error of the mean could not be calculated.
[2]
No participants were analyzed in this treatment group for this timepoint.
13.Secondary Outcome
Title Pain Intensity Scores as Assessed By Visual Analog Scale (VAS)
Hide Description The participant assessed their pain on a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as “no pain” and the right-hand extreme equals 100 mm as “unbearable pain”. A negative change indicated improvement.
Time Frame BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; n = number of participants assessed for a specific parameter at a given visit.
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Mean (Standard Error)
Unit of Measure: mm
BL (n=275,284) 21.1  (1.42) 17.9  (1.25)
Week 4 (n=234,249) 14.6  (1.17) 13.3  (1.11)
Week 7 (n=181,219) 11.1  (1.15) 13.8  (1.31)
Week 10 (n=174, 202) 14.5  (1.46) 12.9  (1.30)
Week 13 (n=152,181) 11.3  (1.37) 12.2  (1.35)
Week 16 (n=121,165) 14.0  (1.77) 12.8  (1.53)
Week 19 (n=114,142) 15.4  (1.92) 12.0  (1.43)
Week 22 (n=79,141) 13.3  (2.20) 15.1  (1.81)
Week 25 (n=64,124) 12.7  (2.39) 11.0  (1.50)
Week 28 (n=47,111) 8.6  (1.85) 12.3  (1.80)
Week 31 (n=45,95) 8.7  (2.11) 12.5  (1.92)
Week 34 (n=37,86) 9.4  (2.90) 10.7  (1.79)
Week 37 (n=29,64) 15.5  (4.08) 10.9  (2.22)
Week 40 (n=24,54) 16.4  (4.20) 8.8  (1.99)
Week 43 (n=12,43) 12.6  (5.04) 7.2  (2.15)
Week 46 (n=14,41) 16.1  (6.11) 7.4  (2.30)
Week 49 (n=10,36) 7.2  (3.71) 6.5  (2.09)
Week 52 (n=8,30) 5.8  (3.43) 6.9  (2.75)
Week 55 (n=6,24) 2.3  (1.20) 3.3  (1.48)
Week 58 (n=6,20) 4.7  (2.20) 3.8  (1.91)
Week 61 (n=4,17) 5.3  (3.04) 7.2  (5.03)
Week 64 (n=3,20) 2.0  (1.00) 6.8  (3.14)
Week 67 (n=4,17) 1.5  (0.96) 8.9  (5.04)
Week 70 (n=3,13) 1.3  (1.33) 1.3  (1.15)
Week 73 (n=3,10) 1.0  (0.58) 16.5  (8.30)
Week 76 (n=3,8) 1.7  (0.88) 12.9  (11.12)
Week 79 (n=3,9) 1.0  (0.58) 5.9  (3.89)
Week 82 (n=2,6) 0.0  (0.00) 4.8  (4.83)
Week 85 (n=2,6) 1.0  (1.00) 6.3  (6.14)
Week 88 (n=2,6) 0.5  (0.50) 5.7  (5.47)
Week 91 (n=2,4) 0.5  (0.50) 7.5  (6.85)
Week 94 (n=2,6) 0.5  (0.50) 5.8  (5.83)
Week 97 (n=1,5) 0.0 [1]   (NA) 0.2  (0.20)
Week 100 (n=1,4) 0.0 [1]   (NA) 0.3  (.25)
Week 103 (n=1,4) 0.0 [1]   (NA) 6.5  (5.85)
Week 106 (n=1,4) 0.0 [1]   (NA) 7.8  (6.79)
Week 109 (n=1,4) 0.0 [1]   (NA) 7.3  (7.25)
Week 112 (n=1,5) 0.0 [1]   (NA) 4.2  (3.50)
Week 115 (n=1,4) 0.0 [1]   (NA) 5.8  (5.11)
Week 118 (n=1,5) 0.0 [1]   (NA) 3.8  (3.32)
Week 121 (n=1,5) 0.0 [1]   (NA) 3.2  (3.20)
Week 124 (n=1,4) 0.0 [1]   (NA) 4.5  (3.84)
Week 127 (n=1,3) 0.0 [1]   (NA) 6.3  (6.33)
Week 130 (n=0,3) NA [2]   (NA) 5.7  (5.67)
Week 133 (n=1,3) 0.0 [1]   (NA) 5.0  (5.00)
Week 136 (n=0,2) NA [2]   (NA) 6.0  (6.00)
Week 139 (n=0,2) NA [2]   (NA) 8.0  (8.00)
Week 142 (n=0,2) NA [2]   (NA) 7.5  (7.50)
Week 145 (n=0,1) NA [2]   (NA) 15.0 [1]   (NA)
Final visit/withdrawal (n=157,161) 23.8  (1.99) 21.9  (2.18)
[1]
Only 1 participant was analyzed in this treatment group at this timepoint, therefore standard error of the mean could not be calculated.
[2]
No participants were analyzed in this treatment group for this timepoint.
14.Secondary Outcome
Title Percentage of Participants With a Change in Analgesic Medication During the Study
Hide Description Analgesic medications were recorded throughout the study until disease progression.
Time Frame BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Measure Type: Number
Unit of Measure: percentage of participants
Taking any analgesic medication 29.0 29.3
Discontinued at least 1 medication 5.9 1.7
Decreased dose of at least 1 medication 0.3 0.3
No change in any medication 5.5 7.1
Increased dose or added at least 1 medication 17.2 20.1
15.Secondary Outcome
Title Body Weight (Kilograms [kg]) at BL
Hide Description [Not Specified]
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 290 294
Median (Full Range)
Unit of Measure: kg
60
(28 to 105)
61
(35 to 110)
16.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Body Weight by Percentage Change in Weight
Hide Description Change in body weight was categorized as an increase of greater than (>)5 percent (%), no change (plus or minus [±]5%), decrease of >5-10%, or a decrease of >10% from BL to the end of study. Time windows were applied in order to assign visits to weight measurements, and the lowest post-screening value recorded was used for the analysis. The percentage change in weight from screening was summarized over time.
Time Frame BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. 273 and 283 participants were analyzed in the Fluoropyrimidine, Cisplatin and Trastuzumab, Fluoropyrimidine, Cisplatin groups, respectively.
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15.
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 273 283
Measure Type: Number
Unit of Measure: percentage of participants
Increase >5% 1.5 1.1
No change (±5%) 51.6 50.5
Decrease >5-10% 28.2 27.2
Decrease >10% 18.7 21.2
17.Secondary Outcome
Title Steady State Trastuzumab Area Under the Concentration (AUC)
Hide Description Individual steady state predicted exposure, as assessed by median AUC (measured as mg multiplied by [*] day per liter [L]) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion. Individual steady state AUC was calculated using all available PK samples from all timepoints.
Time Frame Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: all participants with at least 1 measurement of trastuzumab serum concentration associated with a documented trastuzumab dosing history.
Arm/Group Title Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 266
Median (90% Confidence Interval)
Unit of Measure: mg*day/L
1030
(565 to 1726)
18.Secondary Outcome
Title Trastuzumab Minimum Serum Concentration (Cmin)
Hide Description Median Cmin (measured as milligrams per liter [mg/L]) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion.
Time Frame Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 266
Median (90% Confidence Interval)
Unit of Measure: mg/L
23.0
(6.4 to 48.5)
19.Secondary Outcome
Title Trastuzumab Maximum Serum Concentration (Cmax)
Hide Description Median Cmax (measured as mg/L) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion.
Time Frame Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description:
Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
Overall Number of Participants Analyzed 266
Median (90% Confidence Interval)
Unit of Measure: mg/L
128
(93.1 to 178)
Time Frame Adverse events were recorded from study start to 6 months after treatment completion. Drug-related Serious Adverse Events are collected through study and follow-up regardless of the time elapsed, or if the study has been closed.
Adverse Event Reporting Description The safety analysis population included all patients who received at least one dose of trial treatment and had at least one safety follow-up.
 
Arm/Group Title Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Hide Arm/Group Description Participants received fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles as follows: cisplatin 80 mg/m^2, IV, on Day 1 and EITHER: 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2, tablets, PO, BID from the evening of Day 1 through the morning of Day 15. Participants received trastuzumab plus fluoropyrimidine (EITHER 5-FU or capecitabine, at the investigator’s discretion) and cisplatin once every 3 weeks (one cycle) for a maximum of 6 cycles (except as noted) as follows: trastuzumab 8 mg/kg, IV, on Day 1 (Cycle 1), followed by 6 mg/kg, IV (Cycles 2 onward, administered until disease progression); cisplatin 80 mg/m^2 IV on Day 1; and EITHER 5-FU 800 mg/m^2 continuous IV infusion on Days 1 through 5 OR capecitabine 1000 mg/m^2 tablets, PO BID from the evening of Day 1 through the morning of Day 15.
All-Cause Mortality
Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Fluoropyrimidine/Cisplatin (FP) Trastuzumab + Fluoropyrimidine/Cisplatin (FP + H)
Affected / at Risk (%) Affected / at Risk (%)
Total   81/290 (27.93%)   106/294 (36.05%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  8/290 (2.76%)  11/294 (3.74%) 
Anaemia * 1  7/290 (2.41%)  4/294 (1.36%) 
Neutropenia * 1  3/290 (1.03%)  3/294 (1.02%) 
Pancytopenia * 1  3/290 (1.03%)  0/294 (0.00%) 
Disseminated intravascular coagulation * 1  0/290 (0.00%)  1/294 (0.34%) 
Haematotoxicity * 1  0/290 (0.00%)  1/294 (0.34%) 
Leukopenia * 1  0/290 (0.00%)  2/294 (0.68%) 
Thrombocytopenia * 1  0/290 (0.00%)  1/294 (0.34%) 
Cardiac disorders     
Cardiac failure * 1  2/290 (0.69%)  1/294 (0.34%) 
Myocardial infarction * 1  2/290 (0.69%)  0/294 (0.00%) 
Acute myocardial infarction * 1  0/290 (0.00%)  1/294 (0.34%) 
Angina unstable * 1  0/290 (0.00%)  1/294 (0.34%) 
Cardiac arrest * 1  1/290 (0.34%)  0/294 (0.00%) 
Cardio-respiratory arrest * 1  1/290 (0.34%)  0/294 (0.00%) 
Cardiac failure congestive * 1  0/290 (0.00%)  1/294 (0.34%) 
Congenital, familial and genetic disorders     
Pyloric stenosis * 1  2/290 (0.69%)  0/294 (0.00%) 
Gastrointestinal disorders     
Diarrhoea * 1  6/290 (2.07%)  18/294 (6.12%) 
Vomiting * 1  3/290 (1.03%)  8/294 (2.72%) 
Dysphagia * 1  0/290 (0.00%)  9/294 (3.06%) 
Nausea * 1  4/290 (1.38%)  3/294 (1.02%) 
Abdominal pain * 1  3/290 (1.03%)  1/294 (0.34%) 
Gastrointestinal haemorrage * 1  2/290 (0.69%)  3/294 (1.02%) 
Abdominal pain upper * 1  0/290 (0.00%)  2/294 (0.68%) 
Enteritis * 1  1/290 (0.34%)  1/294 (0.34%) 
Gastric haemorrhage * 1  1/290 (0.34%)  2/294 (0.68%) 
Gastric perforation * 1  0/290 (0.00%)  2/294 (0.68%) 
Gastrointestinal obstruction * 1  2/290 (0.69%)  0/294 (0.00%) 
Ileus * 1  1/290 (0.34%)  1/294 (0.34%) 
Obstruction gastric * 1  1/290 (0.34%)  1/294 (0.34%) 
Peritonitus * 1  2/290 (0.69%)  0/294 (0.00%) 
Abdominal distension * 1  1/290 (0.34%)  0/294 (0.00%) 
Constipation * 1  1/290 (0.34%)  0/294 (0.00%) 
Enterocolitis * 1  0/290 (0.00%)  1/294 (0.34%) 
Gastric ulcer * 1  0/290 (0.00%)  1/294 (0.34%) 
Gastritis * 1