Trial Outcomes & Findings for A Study of Induction and Maintenance Treatment of Advanced Non-squamous Non-Small Cell Lung Cancer (NCT NCT00789373)
NCT ID: NCT00789373
Last Updated: 2018-12-14
Results Overview
Investigator-assessed objective PFS was measured from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For patients not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
939 participants
Primary outcome timeframe
Date of randomization to the date of measured PD or date of death from any cause (up to 19.3 months)
Results posted on
2018-12-14
Participant Flow
Participant milestones
| Measure |
Induction Pemetrexed + Cisplatin
pemetrexed: 500 mg/m\^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles.
cisplatin: 75 mg/m\^2, IV, on Day 1 of each 21-day cycle for 4 cycles.
|
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
Following Induction, received 500 mg/m\^2 maintenance pemetrexed, IV, on Day 1 of each 21-day cycle plus Best Supportive Care until progressive disease (PD) or treatment discontinuation.
|
Pemetrexed + Cisplatin Followed by Placebo
Following Induction, received placebo (normal saline \[0.9% sodium chloride\]) administered IV on Day 1 of every 21-day cycle plus Best Supportive Care until PD or treatment discontinuation.
|
|---|---|---|---|
|
Induction
STARTED
|
939
|
0
|
0
|
|
Induction
COMPLETED
|
540
|
0
|
0
|
|
Induction
NOT COMPLETED
|
399
|
0
|
0
|
|
Maintenance
STARTED
|
0
|
359
|
180
|
|
Maintenance
COMPLETED
|
0
|
0
|
0
|
|
Maintenance
NOT COMPLETED
|
0
|
359
|
180
|
Reasons for withdrawal
| Measure |
Induction Pemetrexed + Cisplatin
pemetrexed: 500 mg/m\^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles.
cisplatin: 75 mg/m\^2, IV, on Day 1 of each 21-day cycle for 4 cycles.
|
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
Following Induction, received 500 mg/m\^2 maintenance pemetrexed, IV, on Day 1 of each 21-day cycle plus Best Supportive Care until progressive disease (PD) or treatment discontinuation.
|
Pemetrexed + Cisplatin Followed by Placebo
Following Induction, received placebo (normal saline \[0.9% sodium chloride\]) administered IV on Day 1 of every 21-day cycle plus Best Supportive Care until PD or treatment discontinuation.
|
|---|---|---|---|
|
Induction
Adverse Event
|
64
|
0
|
0
|
|
Induction
Death Due to study disease
|
24
|
0
|
0
|
|
Induction
Death due to adverse event
|
19
|
0
|
0
|
|
Induction
Death due to toxicity
|
11
|
0
|
0
|
|
Induction
Death due to procedure
|
1
|
0
|
0
|
|
Induction
Investigator decision
|
7
|
0
|
0
|
|
Induction
Protocol entry criteria not met
|
9
|
0
|
0
|
|
Induction
Lost to Follow-up
|
6
|
0
|
0
|
|
Induction
Protocol Violation
|
1
|
0
|
0
|
|
Induction
Progressive Disease
|
220
|
0
|
0
|
|
Induction
Withdrawal by Subject
|
37
|
0
|
0
|
|
Maintenance
Adverse Event
|
0
|
65
|
12
|
|
Maintenance
Death due to study disease
|
0
|
3
|
1
|
|
Maintenance
Death due to adverse event
|
0
|
4
|
1
|
|
Maintenance
Death due to toxicity
|
0
|
1
|
2
|
|
Maintenance
Investigator Decision
|
0
|
4
|
2
|
|
Maintenance
Protocol entry criteria not met
|
0
|
2
|
0
|
|
Maintenance
Lost to Follow-up
|
0
|
2
|
0
|
|
Maintenance
Progressive Disease
|
0
|
253
|
152
|
|
Maintenance
Withdrawal by Subject
|
0
|
21
|
8
|
|
Maintenance
Sponsor Decision
|
0
|
0
|
2
|
|
Maintenance
Participants On-Going at Data Cut-Off
|
0
|
4
|
0
|
Baseline Characteristics
A Study of Induction and Maintenance Treatment of Advanced Non-squamous Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Induction Pemetrexed + Cisplatin
n=939 Participants
pemetrexed plus cisplatin
|
|---|---|
|
Age, Continuous
|
61.3 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
362 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
577 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
59 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African
|
7 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
871 participants
n=5 Participants
|
|
Region of Enrollment
Portugal
|
38 participants
n=5 Participants
|
|
Region of Enrollment
Greece
|
34 participants
n=5 Participants
|
|
Region of Enrollment
Finland
|
18 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
65 participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
33 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
71 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
175 participants
n=5 Participants
|
|
Region of Enrollment
India
|
54 participants
n=5 Participants
|
|
Region of Enrollment
France
|
106 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
34 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
53 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
55 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
48 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
126 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
|
Smoking Status
Ever Smoker
|
757 participants
n=5 Participants
|
|
Smoking Status
Never Smoker
|
175 participants
n=5 Participants
|
|
Smoking Status
Unknown
|
7 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Date of randomization to the date of measured PD or date of death from any cause (up to 19.3 months)Population: All randomized participants
Investigator-assessed objective PFS was measured from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For patients not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Investigator-assessed Objective Progression-free Survival (PFS)
|
4.11 months
Interval 3.15 to 4.57
|
2.83 months
Interval 2.6 to 3.12
|
SECONDARY outcome
Timeframe: Date of randomization to first date of measured PD or date of death from any cause (up to 19.3 months)Population: Randomized participants with reviewable scan--(316/359 \[88%\] Maintenance arm and 156/180 \[87%\] Placebo comparator arm. The majority of unread scans (12.4%) were due to participants not completing 1 cycle of treatment by the data cutoff date (30 June 2010).
To further evaluate the robustness of the PFS analysis, Lilly established an independent review of PFS to assess the potential for investigator bias in the determination of objective PD. PFS was measured from the date of randomization to the first date of objectively determined PD or death. For patients alive as of the data cutoff date and who did not have PD, PFS was censored at the date of the last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=316 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=156 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Independently-assessed Objective Progression-free Survival (PFS)
|
3.94 months
Interval 2.96 to 4.24
|
2.60 months
Interval 2.23 to 2.92
|
SECONDARY outcome
Timeframe: Date of randomization to the date of death from any cause up to 39.5 monthsPopulation: All randomized participants. In the Pemetrexed maintenance arm 103 (28.7%) participants were censored and in the Placebo maintenance arm 39 (21.7%) participants were censored.
OS is the duration from enrollment to death. For patients who are alive, OS is censored at the last contact.
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Overall Survival (OS)
|
13.86 months
Interval 12.75 to 16.03
|
11.01 months
Interval 9.95 to 12.52
|
SECONDARY outcome
Timeframe: Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months)Population: Participants who were randomized and completed the EQ-5D at baseline and at least once post-baseline. For Cycle 17 and 18, there is no data available for the pemetrexed + cisplatin followed by placebo arm. No participants completed so zero participants were analyzed.
The EQ-5D is a generic instrument that describes health status in 5 attributes (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) using a three level scale (no problem, some problems, and major problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score range from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=303 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=153 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 2 Day 1
|
0.0 units on a scale
Standard Deviation 0.19
|
0.01 units on a scale
Standard Deviation 0.17
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Baseline
|
0.77 units on a scale
Standard Deviation 0.21
|
0.79 units on a scale
Standard Deviation 0.18
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 1 Day 1
|
0.01 units on a scale
Standard Deviation 0.15
|
-0.01 units on a scale
Standard Deviation 0.17
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 3 Day 1
|
0.0 units on a scale
Standard Deviation 0.15
|
0.03 units on a scale
Standard Deviation 0.17
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 4 Day 1
|
-0.01 units on a scale
Standard Deviation 0.15
|
0.02 units on a scale
Standard Deviation 0.18
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 5 Day 1
|
0.01 units on a scale
Standard Deviation 0.16
|
0.01 units on a scale
Standard Deviation 0.22
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 6 Day 1
|
-0.02 units on a scale
Standard Deviation 0.18
|
0.04 units on a scale
Standard Deviation 0.14
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 7 Day 1
|
0.01 units on a scale
Standard Deviation 0.20
|
0.01 units on a scale
Standard Deviation 0.13
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 8 Day 1
|
0.01 units on a scale
Standard Deviation 0.18
|
0.05 units on a scale
Standard Deviation 0.15
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 9 Day 1
|
-0.03 units on a scale
Standard Deviation 0.20
|
0.06 units on a scale
Standard Deviation 0.18
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 10 Day 1
|
0.0 units on a scale
Standard Deviation 0.16
|
0.08 units on a scale
Standard Deviation 0.15
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 11 Day 1
|
-0.02 units on a scale
Standard Deviation 0.19
|
0.04 units on a scale
Standard Deviation 0.17
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 12 Day 1
|
-0.06 units on a scale
Standard Deviation 0.27
|
0.06 units on a scale
Standard Deviation 0.16
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 13 Day 1
|
-0.01 units on a scale
Standard Deviation 0.27
|
0.0 units on a scale
Standard Deviation 0.0
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 14 Day 1
|
0.03 units on a scale
Standard Deviation 0.26
|
0.03 units on a scale
Standard Deviation 0.05
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 15 Day 1
|
-0.07 units on a scale
Standard Deviation 0.34
|
0.01 units on a scale
Standard Deviation 0.02
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 16 Day 1
|
-0.01 units on a scale
Standard Deviation 0.36
|
0.0 units on a scale
Standard Deviation 0.0
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 17 Day 1
|
0.32 units on a scale
Standard Deviation 0.43
|
—
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
Cycle 18 Day 1
|
0.45 units on a scale
Standard Deviation 0.52
|
—
|
|
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score
30 Day Post-Study Visit
|
-0.13 units on a scale
Standard Deviation 0.27
|
-0.09 units on a scale
Standard Deviation 0.26
|
SECONDARY outcome
Timeframe: Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months)Population: Participants who were randomized and completed the EQ-5D at baseline and at least once post-baseline. For Cycle 17 and 18, there is no data available for the pemetrexed + cisplatin followed by placebo arm. No participants completed so zero participants were analyzed.
Patients indicate their present health state through completion of the VAS. Possible scores range from 0 (worst imaginable health state) to 100 (best imaginable health state).
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=300 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=148 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 18 Day 1
|
5.0 units on a scale
Standard Deviation 14.1
|
—
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
30 days post-study
|
-4.77 units on a scale
Standard Deviation 17.3
|
-3.92 units on a scale
Standard Deviation 16.7
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Baseline
|
71.1 units on a scale
Standard Deviation 16.6
|
71.0 units on a scale
Standard Deviation 15.8
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 1 Day 1
|
1.65 units on a scale
Standard Deviation 9.86
|
1.42 units on a scale
Standard Deviation 10.2
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 2 Day 1
|
1.24 units on a scale
Standard Deviation 11.2
|
3.15 units on a scale
Standard Deviation 13.0
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 3 Day 1
|
1.82 units on a scale
Standard Deviation 10.9
|
4.90 units on a scale
Standard Deviation 16.9
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 4 Day 1
|
0.69 units on a scale
Standard Deviation 13.1
|
6.15 units on a scale
Standard Deviation 16.4
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 5 Day 1
|
1.55 units on a scale
Standard Deviation 12.4
|
5.99 units on a scale
Standard Deviation 13.1
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 6 Day 1
|
3.01 units on a scale
Standard Deviation 12.5
|
5.76 units on a scale
Standard Deviation 12.9
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 7 Day 1
|
2.7 units on a scale
Standard Deviation 14.5
|
3.98 units on a scale
Standard Deviation 10.9
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 8 Day 1
|
4.12 units on a scale
Standard Deviation 14.1
|
7.58 units on a scale
Standard Deviation 14.8
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 9 Day 1
|
4.19 units on a scale
Standard Deviation 14.2
|
7.61 units on a scale
Standard Deviation 16.7
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 10 Day 1
|
5.14 units on a scale
Standard Deviation 15.1
|
6.23 units on a scale
Standard Deviation 18.7
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 11 Day 1
|
2.58 units on a scale
Standard Deviation 14.7
|
0.94 units on a scale
Standard Deviation 15.4
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 12 Day 1
|
2.11 units on a scale
Standard Deviation 16.0
|
4.63 units on a scale
Standard Deviation 13.1
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 13 Day 1
|
6.29 units on a scale
Standard Deviation 16.4
|
10.0 units on a scale
Standard Deviation 3.27
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 14 Day 1
|
3.64 units on a scale
Standard Deviation 18.4
|
14.0 units on a scale
Standard Deviation 4.55
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 15 Day 1
|
8.40 units on a scale
Standard Deviation 12.9
|
12.0 units on a scale
Standard Deviation 3.46
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 16 Day 1
|
5.83 units on a scale
Standard Deviation 9.99
|
15.0 units on a scale
Standard Deviation 0.0
|
|
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS)
Cycle 17 Day 1
|
15.7 units on a scale
Standard Deviation 21.1
|
—
|
SECONDARY outcome
Timeframe: Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months)Population: All randomized participants
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Percentage of Participants With Hospitalizations Due to Adverse Events or Requiring Transfusion (Resource Utilization)
Hospitalization due to Drug-related Adverse Event
|
8.4 percentage of participants
|
3.3 percentage of participants
|
|
Percentage of Participants With Hospitalizations Due to Adverse Events or Requiring Transfusion (Resource Utilization)
Transfusions Packed Red Blood Cells
|
12.3 percentage of participants
|
4.4 percentage of participants
|
|
Percentage of Participants With Hospitalizations Due to Adverse Events or Requiring Transfusion (Resource Utilization)
Transfusions Whole Blood
|
1.4 percentage of participants
|
0.6 percentage of participants
|
|
Percentage of Participants With Hospitalizations Due to Adverse Events or Requiring Transfusion (Resource Utilization)
Transfusions Platelets
|
1.4 percentage of participants
|
0.6 percentage of participants
|
|
Percentage of Participants With Hospitalizations Due to Adverse Events or Requiring Transfusion (Resource Utilization)
Transfusions Fresh Frozen Plasma
|
0 percentage of participants
|
0.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline randomization through 30-day post-discontinuation visit (up to 49.7 months)Population: Randomized population with 2% cut-off threshold for inclusion for 19.3 months and 5% for 49.7 months.
A summary of non-serious AEs is located in the Reported Adverse Event Module.
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Percentage of Participants With a Non-Serious Adverse Event (AE) During Maintenance Phase
Non-Serious AEs at 2% Threshold: up to 19.3 Month
|
59.9 percentage of participants
|
50.6 percentage of participants
|
|
Percentage of Participants With a Non-Serious Adverse Event (AE) During Maintenance Phase
Non-Serious AEs at 5% Threshold: up to 49.7 Months
|
75.5 percentage of participants
|
62.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline randomization through 30-day post-discontinuation visit (up to 49.7 months)Population: Randomized population with all serious adverse events included.
A summary of serious adverse events is located in the Reported Adverse Event Module.
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Percentage of Participants With Serious Adverse Events During Maintenance Phase
Serious Adverse Events: up to 19.3 Months
|
18.9 percentage of participants
|
12.2 percentage of participants
|
|
Percentage of Participants With Serious Adverse Events During Maintenance Phase
Serious Adverse Events: up to 49.7 Months
|
26.2 percentage of participants
|
20.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to date of measured progressive disease (up to 19.3 months)Population: All randomized participants
Analysis for combined phases was not performed since response was calculated separately for each phase of study. Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response(PR)is at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease(PD) is at least a 20% increase in sum of longest diameter of target lesions; Stable Disease(SD)=no change or small changes that do not meet the above criteria for CR, PR, or PD.
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Percentage of Participants With Objective Tumor Response (Response Rate) During Maintenance Phase of Study up to Primary Data Cut-Off
|
46.2 percentage of participants
|
42.2 percentage of participants
|
SECONDARY outcome
Timeframe: Date of randomization to date of measured PD (up to 19.3 months)Population: All randomized participants
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) is at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=no change or small changes that do not meet the above criteria for CR, PR, or PD. Response Rate = (CR+PR)/Participants in Arm\*100. Disease Control Rate=(CR+PR+SD)/Number of Participants in Arm\*100.
Outcome measures
| Measure |
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 Participants
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 Participants
pemetrexed + cisplatin followed by placebo plus best supportive care
|
|---|---|---|
|
Percentage of Participants With Independently-Assessed Objective Tumor Response (Response Rate) During Maintenance Phase Up to Primary Data Cut-Off
Response Rate
|
46.2 percentage of participants
Interval 41.0 to 51.6
|
42.2 percentage of participants
Interval 34.9 to 49.8
|
|
Percentage of Participants With Independently-Assessed Objective Tumor Response (Response Rate) During Maintenance Phase Up to Primary Data Cut-Off
Disease Control Rate
|
98.1 percentage of participants
Interval 96.0 to 99.2
|
94.4 percentage of participants
Interval 90.0 to 97.3
|
Adverse Events
Induction Pemetrexed + Cisplatin
Serious events: 257 serious events
Other events: 759 other events
Deaths: 0 deaths
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
Serious events: 94 serious events
Other events: 287 other events
Deaths: 0 deaths
Pemetrexed + Cisplatin Followed by Placebo
Serious events: 36 serious events
Other events: 117 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Induction Pemetrexed + Cisplatin
n=939 participants at risk
pemetrexed: 500 mg/m\^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles.
cisplatin: 75 mg/m\^2, IV, on Day 1 of each 21-day cycle for 4 cycles.
|
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 participants at risk
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 participants at risk
pemetrexed and cisplatin followed by placebo plus best supportive care
|
|---|---|---|---|
|
Psychiatric disorders
Depression
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Psychiatric disorders
Hallucination
|
0.11%
1/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Renal and urinary disorders
Bladder diverticulum
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Renal and urinary disorders
Incontinence
|
0.11%
1/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Renal and urinary disorders
Renal failure
|
0.53%
5/939 • Number of events 7 • From start of study up to approximately 108 months
|
1.1%
4/359 • Number of events 7 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Renal and urinary disorders
Renal failure acute
|
0.75%
7/939 • Number of events 9 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Renal and urinary disorders
Renal impairment
|
0.21%
2/939 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Renal and urinary disorders
Renal tubular necrosis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Renal and urinary disorders
Urinary retention
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Reproductive system and breast disorders
Testicular pain
|
0.17%
1/577 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/201 • From start of study up to approximately 108 months
|
0.00%
0/112 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Anaemia
|
1.4%
13/939 • Number of events 30 • From start of study up to approximately 108 months
|
3.1%
11/359 • Number of events 21 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Bone marrow failure
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Febrile bone marrow aplasia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.3%
12/939 • Number of events 13 • From start of study up to approximately 108 months
|
1.7%
6/359 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.32%
3/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.85%
8/939 • Number of events 9 • From start of study up to approximately 108 months
|
1.7%
6/359 • Number of events 8 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.75%
7/939 • Number of events 9 • From start of study up to approximately 108 months
|
1.4%
5/359 • Number of events 8 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Acute coronary syndrome
|
0.11%
1/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Acute myocardial infarction
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.11%
1/939 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Atrial tachycardia
|
0.11%
1/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Atrial thrombosis
|
0.11%
1/939 • Number of events 5 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Cardiac arrest
|
0.32%
3/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Cardiac failure congestive
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Cardiac tamponade
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.32%
3/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Diastolic dysfunction
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Myocardial infarction
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Myocardial ischaemia
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Palpitations
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Pericardial effusion
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Pericarditis
|
0.11%
1/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 5 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Sinus tachycardia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Tachyarrhythmia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Tachycardia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Cardiac disorders
Ventricular fibrillation
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Ear and labyrinth disorders
Vertigo
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Eye disorders
Cataract
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 14 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Eye disorders
Diabetic retinopathy
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Abdominal adhesions
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.32%
3/939 • Number of events 11 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Colitis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Constipation
|
0.64%
6/939 • Number of events 8 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.75%
7/939 • Number of events 9 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Diverticular perforation
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Dyspepsia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Dysphagia
|
0.43%
4/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.11%
1/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Haematemesis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Ileus
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Nausea
|
2.6%
24/939 • Number of events 41 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 5 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Neutropenic colitis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Stomatitis
|
0.32%
3/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Vomiting
|
3.1%
29/939 • Number of events 36 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
General disorders
Asthenia
|
0.53%
5/939 • Number of events 9 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Chest pain
|
0.75%
7/939 • Number of events 17 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 17 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Death
|
0.53%
5/939 • Number of events 5 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Fatigue
|
0.75%
7/939 • Number of events 22 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 4 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 3 • From start of study up to approximately 108 months
|
|
General disorders
General physical health deterioration
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Mucosal inflammation
|
0.75%
7/939 • Number of events 10 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Multi-organ failure
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Oedema peripheral
|
0.11%
1/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Pain
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
General disorders
Pyrexia
|
1.1%
10/939 • Number of events 13 • From start of study up to approximately 108 months
|
1.1%
4/359 • Number of events 5 • From start of study up to approximately 108 months
|
1.1%
2/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
General disorders
Sudden death
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
General disorders
Thrombosis in device
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 10 • From start of study up to approximately 108 months
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Anal abscess
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 5 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Cellulitis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 7 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Device related infection
|
0.21%
2/939 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Endocarditis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Erysipelas
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 10 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Herpes zoster
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Infection
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Lobar pneumonia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Lower respiratory tract infection
|
0.32%
3/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Infections and infestations
Lung abscess
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Lung infection
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Lung infection pseudomonal
|
0.11%
1/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Oral candidiasis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Peritonitis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Pneumonia
|
1.8%
17/939 • Number of events 25 • From start of study up to approximately 108 months
|
1.4%
5/359 • Number of events 8 • From start of study up to approximately 108 months
|
1.7%
3/180 • Number of events 3 • From start of study up to approximately 108 months
|
|
Infections and infestations
Pneumonia pneumococcal
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Postoperative wound infection
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Respiratory tract infection
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Rotavirus infection
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Scrotal abscess
|
0.00%
0/577 • From start of study up to approximately 108 months
|
0.00%
0/201 • From start of study up to approximately 108 months
|
0.89%
1/112 • Number of events 1 • From start of study up to approximately 108 months
|
|
Infections and infestations
Sepsis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Infections and infestations
Septic shock
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Infections and infestations
Staphylococcal infection
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 3 • From start of study up to approximately 108 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Infections and infestations
Urinary tract infection
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Fracture displacement
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Splenic rupture
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 6 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Tracheal obstruction
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Injury, poisoning and procedural complications
Venous injury
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Biopsy pleura
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Blood creatinine decreased
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Blood creatinine increased
|
0.32%
3/939 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Blood sodium decreased
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
C-reactive protein increased
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Creatinine renal clearance decreased
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Haemoglobin decreased
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Liver function test abnormal
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Investigations
Weight decreased
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Dehydration
|
1.2%
11/939 • Number of events 12 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.11%
1/939 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.21%
2/939 • Number of events 5 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.53%
5/939 • Number of events 5 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.43%
4/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
2.2%
4/180 • Number of events 8 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 9 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.21%
2/939 • Number of events 4 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.11%
1/939 • Number of events 36 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.43%
4/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 5 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 7 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Spinal disorder
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Spondylitis
|
0.11%
1/939 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.11%
1/939 • Number of events 11 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour necrosis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Cerebellar infarction
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Cerebral infarction
|
0.11%
1/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Cerebral ischaemia
|
0.43%
4/939 • Number of events 9 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.64%
6/939 • Number of events 9 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Convulsion
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
1.1%
2/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Dizziness
|
0.43%
4/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.56%
2/359 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Facial paresis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 4 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Headache
|
0.00%
0/939 • From start of study up to approximately 108 months
|
1.4%
5/359 • Number of events 19 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Hemiplegia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Intracranial aneurysm
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 8 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Ischaemic stroke
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Loss of consciousness
|
0.21%
2/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Paraplegia
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Pyramidal tract syndrome
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Speech disorder
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Syncope
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Transient ischaemic attack
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.28%
1/362 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/158 • From start of study up to approximately 108 months
|
0.00%
0/68 • From start of study up to approximately 108 months
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.28%
1/362 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/158 • From start of study up to approximately 108 months
|
0.00%
0/68 • From start of study up to approximately 108 months
|
|
Psychiatric disorders
Anxiety
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 4 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.6%
15/939 • Number of events 26 • From start of study up to approximately 108 months
|
1.7%
6/359 • Number of events 12 • From start of study up to approximately 108 months
|
1.7%
3/180 • Number of events 4 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.32%
3/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.2%
11/939 • Number of events 28 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 1 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.0%
28/939 • Number of events 63 • From start of study up to approximately 108 months
|
0.84%
3/359 • Number of events 14 • From start of study up to approximately 108 months
|
1.7%
3/180 • Number of events 7 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.21%
2/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.32%
3/939 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.56%
1/180 • Number of events 1 • From start of study up to approximately 108 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.11%
1/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Surgical and medical procedures
Catheter removal
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Arterial thrombosis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Arterial thrombosis limb
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Deep vein thrombosis
|
0.43%
4/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Hypertension
|
0.21%
2/939 • Number of events 6 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Iliac artery thrombosis
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 11 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Ischaemic limb pain
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Jugular vein distension
|
0.11%
1/939 • Number of events 2 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Peripheral ischaemia
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Superior vena cava syndrome
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
1.1%
2/180 • Number of events 2 • From start of study up to approximately 108 months
|
|
Vascular disorders
Superior vena caval occlusion
|
0.00%
0/939 • From start of study up to approximately 108 months
|
0.28%
1/359 • Number of events 3 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
|
Vascular disorders
Thrombophlebitis
|
0.11%
1/939 • Number of events 1 • From start of study up to approximately 108 months
|
0.00%
0/359 • From start of study up to approximately 108 months
|
0.00%
0/180 • From start of study up to approximately 108 months
|
Other adverse events
| Measure |
Induction Pemetrexed + Cisplatin
n=939 participants at risk
pemetrexed: 500 mg/m\^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles.
cisplatin: 75 mg/m\^2, IV, on Day 1 of each 21-day cycle for 4 cycles.
|
Pemetrexed + Cisplatin Followed by Maintenance Pemetrexed
n=359 participants at risk
pemetrexed and cisplatin followed by maintenance pemetrexed plus best supportive care
|
Pemetrexed + Cisplatin Followed by Placebo
n=180 participants at risk
pemetrexed and cisplatin followed by placebo plus best supportive care
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
16.2%
152/939 • Number of events 600 • From start of study up to approximately 108 months
|
21.2%
76/359 • Number of events 295 • From start of study up to approximately 108 months
|
2.8%
5/180 • Number of events 11 • From start of study up to approximately 108 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.8%
158/939 • Number of events 340 • From start of study up to approximately 108 months
|
10.6%
38/359 • Number of events 100 • From start of study up to approximately 108 months
|
1.7%
3/180 • Number of events 4 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Constipation
|
14.0%
131/939 • Number of events 339 • From start of study up to approximately 108 months
|
6.4%
23/359 • Number of events 110 • From start of study up to approximately 108 months
|
7.8%
14/180 • Number of events 47 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Diarrhoea
|
12.1%
114/939 • Number of events 175 • From start of study up to approximately 108 months
|
7.8%
28/359 • Number of events 44 • From start of study up to approximately 108 months
|
3.9%
7/180 • Number of events 16 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Nausea
|
38.6%
362/939 • Number of events 932 • From start of study up to approximately 108 months
|
19.2%
69/359 • Number of events 286 • From start of study up to approximately 108 months
|
4.4%
8/180 • Number of events 15 • From start of study up to approximately 108 months
|
|
Gastrointestinal disorders
Vomiting
|
22.4%
210/939 • Number of events 366 • From start of study up to approximately 108 months
|
11.7%
42/359 • Number of events 78 • From start of study up to approximately 108 months
|
5.0%
9/180 • Number of events 14 • From start of study up to approximately 108 months
|
|
General disorders
Asthenia
|
15.0%
141/939 • Number of events 494 • From start of study up to approximately 108 months
|
14.2%
51/359 • Number of events 325 • From start of study up to approximately 108 months
|
4.4%
8/180 • Number of events 16 • From start of study up to approximately 108 months
|
|
General disorders
Chest pain
|
4.7%
44/939 • Number of events 139 • From start of study up to approximately 108 months
|
5.0%
18/359 • Number of events 77 • From start of study up to approximately 108 months
|
3.3%
6/180 • Number of events 13 • From start of study up to approximately 108 months
|
|
General disorders
Fatigue
|
19.3%
181/939 • Number of events 743 • From start of study up to approximately 108 months
|
15.3%
55/359 • Number of events 316 • From start of study up to approximately 108 months
|
8.9%
16/180 • Number of events 61 • From start of study up to approximately 108 months
|
|
General disorders
Mucosal inflammation
|
5.3%
50/939 • Number of events 83 • From start of study up to approximately 108 months
|
5.8%
21/359 • Number of events 50 • From start of study up to approximately 108 months
|
2.8%
5/180 • Number of events 9 • From start of study up to approximately 108 months
|
|
General disorders
Oedema peripheral
|
4.5%
42/939 • Number of events 168 • From start of study up to approximately 108 months
|
12.5%
45/359 • Number of events 314 • From start of study up to approximately 108 months
|
2.8%
5/180 • Number of events 18 • From start of study up to approximately 108 months
|
|
General disorders
Pyrexia
|
4.9%
46/939 • Number of events 63 • From start of study up to approximately 108 months
|
10.6%
38/359 • Number of events 65 • From start of study up to approximately 108 months
|
3.9%
7/180 • Number of events 7 • From start of study up to approximately 108 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
12.7%
119/939 • Number of events 316 • From start of study up to approximately 108 months
|
8.9%
32/359 • Number of events 91 • From start of study up to approximately 108 months
|
3.3%
6/180 • Number of events 21 • From start of study up to approximately 108 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
31/939 • Number of events 127 • From start of study up to approximately 108 months
|
6.4%
23/359 • Number of events 155 • From start of study up to approximately 108 months
|
3.9%
7/180 • Number of events 15 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Dizziness
|
3.2%
30/939 • Number of events 76 • From start of study up to approximately 108 months
|
5.0%
18/359 • Number of events 55 • From start of study up to approximately 108 months
|
1.7%
3/180 • Number of events 14 • From start of study up to approximately 108 months
|
|
Nervous system disorders
Paraesthesia
|
1.8%
17/939 • Number of events 76 • From start of study up to approximately 108 months
|
4.7%
17/359 • Number of events 118 • From start of study up to approximately 108 months
|
7.2%
13/180 • Number of events 36 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.1%
67/939 • Number of events 250 • From start of study up to approximately 108 months
|
8.1%
29/359 • Number of events 79 • From start of study up to approximately 108 months
|
6.1%
11/180 • Number of events 26 • From start of study up to approximately 108 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.8%
73/939 • Number of events 235 • From start of study up to approximately 108 months
|
12.0%
43/359 • Number of events 201 • From start of study up to approximately 108 months
|
9.4%
17/180 • Number of events 54 • From start of study up to approximately 108 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.1%
48/939 • Number of events 90 • From start of study up to approximately 108 months
|
4.2%
15/359 • Number of events 65 • From start of study up to approximately 108 months
|
5.0%
9/180 • Number of events 13 • From start of study up to approximately 108 months
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60