Trial Outcomes & Findings for A Study for Patients With Head and Neck Cancer (NCT NCT00415194)
NCT ID: NCT00415194
Last Updated: 2011-06-28
Results Overview
OS duration is defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date, OS duration will be censored at the date of the participant's last contact prior to that cut-off date.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
795 participants
Primary outcome timeframe
Baseline to date of death from any cause up to 36 months
Results posted on
2011-06-28
Participant Flow
Participant milestones
| Measure |
Pemetrexed/Cisplatin
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Overall Study
STARTED
|
398
|
397
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
392
|
385
|
|
Overall Study
COMPLETED
|
70
|
55
|
|
Overall Study
NOT COMPLETED
|
328
|
342
|
Reasons for withdrawal
| Measure |
Pemetrexed/Cisplatin
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Overall Study
Adverse Event
|
37
|
32
|
|
Overall Study
Entry Criteria Not Met
|
4
|
8
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
10
|
16
|
|
Overall Study
Progressive Disease
|
180
|
217
|
|
Overall Study
Protocol Violation
|
4
|
2
|
|
Overall Study
Withdrawal by Subject
|
28
|
21
|
|
Overall Study
Death Due to Study Disease
|
26
|
29
|
|
Overall Study
Death Due to Study Drug Related AE
|
11
|
1
|
|
Overall Study
Death Due to Procedural Related AE
|
0
|
1
|
|
Overall Study
Death Due to AE (Other Causes)
|
27
|
15
|
Baseline Characteristics
A Study for Patients With Head and Neck Cancer
Baseline characteristics by cohort
| Measure |
Pemetrexed/Cisplatin
n=398 Participants
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=397 Participants
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Total
n=795 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
57.45 years
STANDARD_DEVIATION 9.54 • n=99 Participants
|
57.78 years
STANDARD_DEVIATION 9.36 • n=107 Participants
|
57.62 years
STANDARD_DEVIATION 9.44 • n=206 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=99 Participants
|
53 Participants
n=107 Participants
|
109 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
342 Participants
n=99 Participants
|
344 Participants
n=107 Participants
|
686 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
African
|
17 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
243 Participants
n=99 Participants
|
233 Participants
n=107 Participants
|
476 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
55 Participants
n=99 Participants
|
65 Participants
n=107 Participants
|
120 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
11 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
West Asian (Indian sub-continent)
|
72 Participants
n=99 Participants
|
70 Participants
n=107 Participants
|
142 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Region of Enrollment
Argentina
|
5 participants
n=99 Participants
|
10 participants
n=107 Participants
|
15 participants
n=206 Participants
|
|
Region of Enrollment
Belgium
|
7 participants
n=99 Participants
|
10 participants
n=107 Participants
|
17 participants
n=206 Participants
|
|
Region of Enrollment
Brazil
|
16 participants
n=99 Participants
|
12 participants
n=107 Participants
|
28 participants
n=206 Participants
|
|
Region of Enrollment
China
|
5 participants
n=99 Participants
|
7 participants
n=107 Participants
|
12 participants
n=206 Participants
|
|
Region of Enrollment
Denmark
|
7 participants
n=99 Participants
|
3 participants
n=107 Participants
|
10 participants
n=206 Participants
|
|
Region of Enrollment
France
|
3 participants
n=99 Participants
|
3 participants
n=107 Participants
|
6 participants
n=206 Participants
|
|
Region of Enrollment
Germany
|
50 participants
n=99 Participants
|
48 participants
n=107 Participants
|
98 participants
n=206 Participants
|
|
Region of Enrollment
Hungary
|
23 participants
n=99 Participants
|
22 participants
n=107 Participants
|
45 participants
n=206 Participants
|
|
Region of Enrollment
India
|
72 participants
n=99 Participants
|
75 participants
n=107 Participants
|
147 participants
n=206 Participants
|
|
Region of Enrollment
Italy
|
19 participants
n=99 Participants
|
21 participants
n=107 Participants
|
40 participants
n=206 Participants
|
|
Region of Enrollment
Korea, Republic of
|
29 participants
n=99 Participants
|
24 participants
n=107 Participants
|
53 participants
n=206 Participants
|
|
Region of Enrollment
Mexico
|
9 participants
n=99 Participants
|
8 participants
n=107 Participants
|
17 participants
n=206 Participants
|
|
Region of Enrollment
Netherlands
|
8 participants
n=99 Participants
|
11 participants
n=107 Participants
|
19 participants
n=206 Participants
|
|
Region of Enrollment
Poland
|
10 participants
n=99 Participants
|
10 participants
n=107 Participants
|
20 participants
n=206 Participants
|
|
Region of Enrollment
Romania
|
20 participants
n=99 Participants
|
22 participants
n=107 Participants
|
42 participants
n=206 Participants
|
|
Region of Enrollment
Russian Federation
|
23 participants
n=99 Participants
|
20 participants
n=107 Participants
|
43 participants
n=206 Participants
|
|
Region of Enrollment
South Africa
|
11 participants
n=99 Participants
|
9 participants
n=107 Participants
|
20 participants
n=206 Participants
|
|
Region of Enrollment
Spain
|
31 participants
n=99 Participants
|
29 participants
n=107 Participants
|
60 participants
n=206 Participants
|
|
Region of Enrollment
Taiwan
|
21 participants
n=99 Participants
|
25 participants
n=107 Participants
|
46 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=99 Participants
|
28 participants
n=107 Participants
|
57 participants
n=206 Participants
|
|
Previously Treated for Head and Neck Cancer (HNC)
No
|
35 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
74 Participants
n=206 Participants
|
|
Previously Treated for Head and Neck Cancer (HNC)
Yes
|
363 Participants
n=99 Participants
|
358 Participants
n=107 Participants
|
721 Participants
n=206 Participants
|
|
Prior Treatment with Platinum-Based Therapy
No
|
213 Participants
n=99 Participants
|
228 Participants
n=107 Participants
|
441 Participants
n=206 Participants
|
|
Prior Treatment with Platinum-Based Therapy
Yes
|
185 Participants
n=99 Participants
|
169 Participants
n=107 Participants
|
354 Participants
n=206 Participants
|
|
Distant Metastasis
No
|
165 Participants
n=99 Participants
|
155 Participants
n=107 Participants
|
320 Participants
n=206 Participants
|
|
Distant Metastasis
Yes
|
233 Participants
n=99 Participants
|
242 Participants
n=107 Participants
|
475 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
90 Participants
n=99 Participants
|
90 Participants
n=107 Participants
|
180 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
257 Participants
n=99 Participants
|
253 Participants
n=107 Participants
|
510 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
2
|
51 Participants
n=99 Participants
|
53 Participants
n=107 Participants
|
104 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Missing Data
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Primary Site of Disease
Hypopharynx
|
63 Participants
n=99 Participants
|
59 Participants
n=107 Participants
|
122 Participants
n=206 Participants
|
|
Primary Site of Disease
Larynx
|
103 Participants
n=99 Participants
|
102 Participants
n=107 Participants
|
205 Participants
n=206 Participants
|
|
Primary Site of Disease
Oral Cavity
|
138 Participants
n=99 Participants
|
123 Participants
n=107 Participants
|
261 Participants
n=206 Participants
|
|
Primary Site of Disease
Oropharynx
|
86 Participants
n=99 Participants
|
106 Participants
n=107 Participants
|
192 Participants
n=206 Participants
|
|
Primary Site of Disease
Other
|
8 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to date of death from any cause up to 36 monthsPopulation: Intention to Treat (ITT) Population - defines the treatment group as those to which participants were assigned by random allocation, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol.
OS duration is defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date, OS duration will be censored at the date of the participant's last contact prior to that cut-off date.
Outcome measures
| Measure |
Pemetrexed/Cisplatin
n=398 Participants
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=397 Participants
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Overall Survival (OS)
|
7.33 Months
Interval 6.34 to 8.38
|
6.28 Months
Interval 5.52 to 7.06
|
SECONDARY outcome
Timeframe: baseline to measured progressive disease up to 33 monthsPopulation: Intention to Treat (ITT) Population - defines the treatment group as those to which participants were assigned by random allocation, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol.
Objective PFS is defined as the time from date of randomization to date of objectively determined progressive disease (PD) or death from any cause, whichever comes first. PD was defined by Response Evaluation Criteria in Solid Tumors (RECIST). PD=at least a 20% increase in sum of longest diameter of target lesions. For participants who are not known to have died as of the data-inclusion cut-off date, and who do not have progressive disease, PFS will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy.
Outcome measures
| Measure |
Pemetrexed/Cisplatin
n=398 Participants
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=397 Participants
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Progression-free Survival (PFS)
|
3.61 months
Interval 3.15 to 4.07
|
2.79 months
Interval 2.69 to 3.22
|
SECONDARY outcome
Timeframe: Baseline to progressive disease or discontinuation of study treatment up to 11 monthsPopulation: Intention to Treat (ITT) Population - defines the treatment group as those to which participants were assigned by random allocation, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol.
Tumor Response is evaluated as CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumors (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Response rate (%) = (number of participants with CR+PR/number of participants)\*100
Outcome measures
| Measure |
Pemetrexed/Cisplatin
n=398 Participants
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=397 Participants
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Percent of Participants With a Tumor Response (Response Rate)
|
12.1 Percentage of participants
|
8.1 Percentage of participants
|
SECONDARY outcome
Timeframe: time of response to progressive disease up to 24 monthsPopulation: ITT population with a confirmed best response of complete response (CR) or partial response (PR).
DoR is time from first observation of complete response (CR) or partial response (PR) to first observation of PD or death. Response is objective status of CR or PR using RECIST criteria. CR is disappearance of lesions. PR is \>30% decrease in size of lesions. Responder is any participant with CR or PR. PD is at least 20% increase in sum of longest diameter of target lesions. For participants alive as of data-inclusion cut-off date and who do not have PD, DoR will be censored at date of last objective progression-free disease assessment before date of any subsequent systemic anticancer therapy.
Outcome measures
| Measure |
Pemetrexed/Cisplatin
n=48 Participants
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=32 Participants
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Duration of Response (DoR)
|
5.29 Months
Interval 4.21 to 5.98
|
4.37 Months
Interval 3.58 to 6.44
|
SECONDARY outcome
Timeframe: Baseline (</=Day 1 of first dose) and Day 1 of every subsequent cycle to 30-day post-study completion up to 33 monthsPopulation: Intention to treat (ITT) population with at least Baseline data.
FACT-H\&N consists of 39 items with 5-point rating scale from 0 (not at all) to 4 (very much). FACT-H\&N Total score ranges from 0 to 148. Higher score represents a better quality of life. Time to worsening was defined as the first date of worsening in the FACT H\&N Total score that was considered at least the prospectively defined minimally important difference (MID) as compared with participant's baseline score, or date of death from any cause. The MID for FACT H\&N Total score was a decrease of 12 points.
Outcome measures
| Measure |
Pemetrexed/Cisplatin
n=271 Participants
Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=270 Participants
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m\^2 on Day 1 every 21 days.
Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.
Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.
Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Time to Treatment Worsening in Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-H&N) Total Score
|
3.29 Months
Interval 2.76 to 4.11
|
2.89 Months
Interval 2.4 to 3.19
|
SECONDARY outcome
Timeframe: BaselinePopulation: Zero participants were analyzed because the relatively low number of samples collected would not have yielded a meaningful genomic analysis.
Correlation between highly up/downregulated genes and clinical response (Overall Survival (OS) and Progression-Free Survival (PFS)). OS is is defined as the time from the date of randomization to the date of death from any cause. PFS is defined as the time from the date of randomization to the date of objectively determined progressive disease or death from any cause, whichever comes first. 0 participants were analyzed; Reason: The relatively low number of samples collected would not have yielded a meaningful genomic analysis and the decision was made to not analyze the data.
Outcome measures
Outcome data not reported
Adverse Events
Pemetrexed/Cisplatin
Serious events: 185 serious events
Other events: 343 other events
Deaths: 0 deaths
Placebo/Cisplatin
Serious events: 132 serious events
Other events: 316 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pemetrexed/Cisplatin
n=392 participants at risk
Pemetrexed 500 milligrams per meter square (mg/m2) administered intravenously (IV) plus cisplatin 75 mg/m2 IV on Day 1 every 21 days. Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment. Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose. Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=385 participants at risk
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m2 on Day 1 every 21 days. Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment. Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose. Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Blood and lymphatic system disorders
Agranulocytosis
|
0.77%
3/392 • Number of events 6
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Anaemia
|
5.6%
22/392 • Number of events 27
Participants who received at least one dose of study drug were included in the safety population included here.
|
4.4%
17/385 • Number of events 20
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Anaemia of malignant disease
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Bone marrow toxicity
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.1%
12/392 • Number of events 13
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Leukopenia
|
3.6%
14/392 • Number of events 16
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.1%
12/392 • Number of events 13
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.78%
3/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.8%
11/392 • Number of events 12
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.78%
3/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.77%
3/392 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Atrial fibrillation
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Atrial flutter
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Cardiac arrest
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Cardiac failure
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.77%
3/392 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Myocardial infarction
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Ear and labyrinth disorders
Deafness
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Ear and labyrinth disorders
Vertigo
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.51%
2/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Aphagia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Constipation
|
1.0%
4/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.6%
14/392 • Number of events 14
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Disbacteriosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Duodenal ulcer perforation
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Dysphagia
|
1.5%
6/392 • Number of events 6
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.78%
3/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Gastric ulcer perforation
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Gastritis
|
0.26%
1/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Gastrointestinal necrosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Glossodynia
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Haematemesis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Ileus
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Intestinal infarction
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Mesenteric artery thrombosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Nausea
|
3.3%
13/392 • Number of events 14
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.8%
7/385 • Number of events 7
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Peritonitis
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Stomatitis
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Tongue oedema
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
22/392 • Number of events 24
Participants who received at least one dose of study drug were included in the safety population included here.
|
2.3%
9/385 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Adhesion
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Asthenia
|
1.5%
6/392 • Number of events 8
Participants who received at least one dose of study drug were included in the safety population included here.
|
2.3%
9/385 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Chest pain
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Chills
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Death
|
1.0%
4/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.0%
4/385 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Face oedema
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Fatigue
|
1.8%
7/392 • Number of events 7
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.3%
5/385 • Number of events 5
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
General physical health deterioration
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Influenza like illness
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Local swelling
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Localised oedema
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Malaise
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Mucosal inflammation
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Multi-organ failure
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Oedema peripheral
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Pain
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Performance status decreased
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Pyrexia
|
2.3%
9/392 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.6%
6/385 • Number of events 7
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Sudden cardiac death
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Abdominal infection
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Abdominal wall abscess
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Abscess
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Acinetobacter infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Bronchopneumonia
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Candida sepsis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Catheter site infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Cellulitis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Central line infection
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Empyema
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Gastroenteritis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Gastrointestinal infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Herpes zoster
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.78%
3/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Lung infection
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Oral infection
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Pneumonia
|
6.6%
26/392 • Number of events 29
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.8%
7/385 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Pseudomonal sepsis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Pseudomonas infection
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Respiratory tract infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Sepsis
|
1.0%
4/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.0%
4/385 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Septic shock
|
0.77%
3/392 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Skin infection
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Staphylococcal infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Staphylococcal sepsis
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Superinfection bacterial
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Tracheitis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Urinary tract infection
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Infections and infestations
Wound infection
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Gastrointestinal stoma complication
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Gastrostomy failure
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.26%
1/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.78%
3/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Injury, poisoning and procedural complications
Tracheal obstruction
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Aspiration bronchial
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Blood alkaline phosphatase increased
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Blood creatinine increased
|
1.0%
4/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Blood electrolytes abnormal
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Blood pressure increased
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Creatinine renal clearance decreased
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
ECG signs of myocardial ischaemia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Glomerular filtration rate decreased
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Haemoglobin decreased
|
1.8%
7/392 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.0%
4/385 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Lymphocyte count decreased
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Neutrophil count decreased
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Platelet count decreased
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Weight decreased
|
0.77%
3/392 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
White blood cell count decreased
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
White blood cell count increased
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Anorexia
|
1.3%
5/392 • Number of events 5
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.3%
5/385 • Number of events 6
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Cachexia
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.3%
9/392 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.8%
7/385 • Number of events 7
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Diabetic foot
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.26%
1/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.5%
6/392 • Number of events 7
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.8%
7/385 • Number of events 7
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.3%
9/392 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.3%
5/385 • Number of events 5
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Shock hypoglycaemic
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oncologic complication
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin neoplasm bleeding
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.0%
4/385 • Number of events 6
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
1.0%
4/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Anoxic encephalopathy
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Cerebral infarction
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Cerebral ischaemia
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Coma
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Convulsion
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.78%
3/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Dizziness
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Encephalitis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Hydrocephalus
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Lethargy
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Loss of consciousness
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Polyneuropathy
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Nervous system disorders
Syncope
|
0.77%
3/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.0%
4/385 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Psychiatric disorders
Depression
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Psychiatric disorders
Disorientation
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Psychiatric disorders
Suicidal ideation
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Renal and urinary disorders
Renal failure
|
1.8%
7/392 • Number of events 9
Participants who received at least one dose of study drug were included in the safety population included here.
|
1.0%
4/385 • Number of events 5
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Renal and urinary disorders
Renal failure acute
|
0.77%
3/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Renal and urinary disorders
Renal impairment
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial secretion retention
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.6%
10/392 • Number of events 10
Participants who received at least one dose of study drug were included in the safety population included here.
|
3.9%
15/385 • Number of events 15
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal dyspnoea
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal oedema
|
1.0%
4/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal stenosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract haemorrhage
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.52%
2/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Upper airway obstruction
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Circulatory collapse
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Embolism
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Femoral artery occlusion
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Haemodynamic instability
|
0.00%
0/392
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Haemorrhage
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.78%
3/385 • Number of events 3
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Hypotension
|
1.0%
4/392 • Number of events 4
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Orthostatic hypotension
|
0.51%
2/392 • Number of events 2
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Peripheral ischaemia
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Phlebitis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Shock
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.26%
1/385 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Shock haemorrhagic
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Superior vena caval occlusion
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Vascular disorders
Venous thrombosis
|
0.26%
1/392 • Number of events 1
Participants who received at least one dose of study drug were included in the safety population included here.
|
0.00%
0/385
Participants who received at least one dose of study drug were included in the safety population included here.
|
Other adverse events
| Measure |
Pemetrexed/Cisplatin
n=392 participants at risk
Pemetrexed 500 milligrams per meter square (mg/m2) administered intravenously (IV) plus cisplatin 75 mg/m2 IV on Day 1 every 21 days. Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment. Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose. Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
Placebo/Cisplatin
n=385 participants at risk
Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m2 on Day 1 every 21 days. Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment. Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose. Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
30.1%
118/392 • Number of events 133
Participants who received at least one dose of study drug were included in the safety population included here.
|
20.5%
79/385 • Number of events 88
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Leukopenia
|
9.7%
38/392 • Number of events 57
Participants who received at least one dose of study drug were included in the safety population included here.
|
6.2%
24/385 • Number of events 35
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Neutropenia
|
17.1%
67/392 • Number of events 105
Participants who received at least one dose of study drug were included in the safety population included here.
|
9.1%
35/385 • Number of events 48
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.1%
28/392 • Number of events 33
Participants who received at least one dose of study drug were included in the safety population included here.
|
4.4%
17/385 • Number of events 22
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Constipation
|
14.3%
56/392 • Number of events 63
Participants who received at least one dose of study drug were included in the safety population included here.
|
13.8%
53/385 • Number of events 65
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
42/392 • Number of events 50
Participants who received at least one dose of study drug were included in the safety population included here.
|
8.6%
33/385 • Number of events 35
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Dysphagia
|
4.8%
19/392 • Number of events 19
Participants who received at least one dose of study drug were included in the safety population included here.
|
5.7%
22/385 • Number of events 23
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Nausea
|
30.1%
118/392 • Number of events 199
Participants who received at least one dose of study drug were included in the safety population included here.
|
27.5%
106/385 • Number of events 153
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Gastrointestinal disorders
Vomiting
|
15.8%
62/392 • Number of events 81
Participants who received at least one dose of study drug were included in the safety population included here.
|
20.5%
79/385 • Number of events 104
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Asthenia
|
9.2%
36/392 • Number of events 41
Participants who received at least one dose of study drug were included in the safety population included here.
|
8.1%
31/385 • Number of events 35
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Fatigue
|
17.1%
67/392 • Number of events 88
Participants who received at least one dose of study drug were included in the safety population included here.
|
13.8%
53/385 • Number of events 57
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Mucosal inflammation
|
6.4%
25/392 • Number of events 30
Participants who received at least one dose of study drug were included in the safety population included here.
|
2.1%
8/385 • Number of events 8
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Pain
|
4.1%
16/392 • Number of events 19
Participants who received at least one dose of study drug were included in the safety population included here.
|
5.2%
20/385 • Number of events 23
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
General disorders
Pyrexia
|
10.2%
40/392 • Number of events 44
Participants who received at least one dose of study drug were included in the safety population included here.
|
4.9%
19/385 • Number of events 21
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Creatinine renal clearance decreased
|
8.2%
32/392 • Number of events 34
Participants who received at least one dose of study drug were included in the safety population included here.
|
8.1%
31/385 • Number of events 36
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Investigations
Weight decreased
|
11.5%
45/392 • Number of events 47
Participants who received at least one dose of study drug were included in the safety population included here.
|
13.0%
50/385 • Number of events 51
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Anorexia
|
13.3%
52/392 • Number of events 63
Participants who received at least one dose of study drug were included in the safety population included here.
|
11.4%
44/385 • Number of events 50
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.4%
25/392 • Number of events 28
Participants who received at least one dose of study drug were included in the safety population included here.
|
3.6%
14/385 • Number of events 15
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
10.2%
40/392 • Number of events 47
Participants who received at least one dose of study drug were included in the safety population included here.
|
7.5%
29/385 • Number of events 30
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.4%
21/392 • Number of events 27
Participants who received at least one dose of study drug were included in the safety population included here.
|
6.2%
24/385 • Number of events 25
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
5.9%
23/392 • Number of events 25
Participants who received at least one dose of study drug were included in the safety population included here.
|
6.0%
23/385 • Number of events 26
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Psychiatric disorders
Insomnia
|
5.9%
23/392 • Number of events 24
Participants who received at least one dose of study drug were included in the safety population included here.
|
6.0%
23/385 • Number of events 23
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
23/392 • Number of events 25
Participants who received at least one dose of study drug were included in the safety population included here.
|
5.2%
20/385 • Number of events 21
Participants who received at least one dose of study drug were included in the safety population included here.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.6%
18/392 • Number of events 19
Participants who received at least one dose of study drug were included in the safety population included here.
|
5.5%
21/385 • Number of events 21
Participants who received at least one dose of study drug were included in the safety population included here.
|
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