Trial Outcomes & Findings for A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer (NCT NCT02614794)
NCT ID: NCT02614794
Last Updated: 2023-08-14
Results Overview
Defined as the time from the date of randomization to the date of documented disease progression.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
612 participants
Primary outcome timeframe
34.6 months
Results posted on
2023-08-14
Participant Flow
Participant milestones
| Measure |
Tuc+Cap+Tra
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Overall Study
STARTED
|
410
|
202
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
410
|
202
|
Reasons for withdrawal
| Measure |
Tuc+Cap+Tra
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Overall Study
Death
|
258
|
151
|
|
Overall Study
Study closure by Sponsor
|
119
|
45
|
|
Overall Study
Withdrawal by Subject
|
24
|
5
|
|
Overall Study
Lost to Follow-up
|
7
|
0
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Hospital closure
|
1
|
0
|
Baseline Characteristics
A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer
Baseline characteristics by cohort
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
Total
n=612 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
328 Participants
n=93 Participants
|
168 Participants
n=4 Participants
|
496 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
82 Participants
n=93 Participants
|
34 Participants
n=4 Participants
|
116 Participants
n=27 Participants
|
|
Age, Continuous
|
55 years
n=93 Participants
|
54 years
n=4 Participants
|
54 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
407 Participants
n=93 Participants
|
200 Participants
n=4 Participants
|
607 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
37 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
51 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
362 Participants
n=93 Participants
|
184 Participants
n=4 Participants
|
546 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
11 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
18 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
41 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
55 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
287 Participants
n=93 Participants
|
157 Participants
n=4 Participants
|
444 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
64 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
90 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
220 Participants
n=93 Participants
|
111 Participants
n=4 Participants
|
331 Participants
n=27 Participants
|
|
Region of Enrollment
France
|
29 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
46 Participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
33 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
45 Participants
n=27 Participants
|
|
Region of Enrollment
Australia
|
27 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
39 Participants
n=27 Participants
|
|
Region of Enrollment
Canada
|
26 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
|
Region of Enrollment
Spain
|
19 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Region of Enrollment
Denmark
|
13 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Region of Enrollment
Germany
|
9 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Region of Enrollment
Israel
|
13 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Region of Enrollment
Belgium
|
4 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Region of Enrollment
Italy
|
6 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Region of Enrollment
Austria
|
6 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Region of Enrollment
Portugal
|
3 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Region of Enrollment
Czech Republic
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Region of Enrollment
Switzerland
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0: Normal activity
|
204 Participants
n=93 Participants
|
94 Participants
n=4 Participants
|
298 Participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1: Symptoms, but ambulatory
|
206 Participants
n=93 Participants
|
108 Participants
n=4 Participants
|
314 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 34.6 monthsPopulation: Intent-to-treat Progression Free Survival (ITT-PFS) Population: Includes the first 480 randomized participants in the ITT analysis population (evaluated by their random treatment assignment).
Defined as the time from the date of randomization to the date of documented disease progression.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=320 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=160 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR)
|
7.8 months
Interval 4.3 to 17.8
|
5.6 months
Interval 3.0 to 9.7
|
SECONDARY outcome
Timeframe: 34.6 monthsPopulation: ITT-PFSBrainMets population: included all randomized participants with brain metastases (evaluated by their random treatment assignment).
Defined as the time from the date of randomization to the date of documented disease progression.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=198 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=93 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR
|
7.6 months
Interval 4.2 to 11.8
|
5.4 months
Interval 3.0 to 7.5
|
SECONDARY outcome
Timeframe: 35.9 monthsPopulation: ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Defined as time from randomization to death from any cause
Outcome measures
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Overall Survival (OS) at Time of Primary Analysis
|
21.9 months
Interval 18.3 to 31.0
|
17.4 months
Interval 13.6 to 19.9
|
SECONDARY outcome
Timeframe: 34.6 monthsPopulation: ITT - PFS population, subset of participants with measurable disease by BICR at baseline. The ITT-PFS Population includes the first 480 randomized participants in the ITT analysis population (evaluated by their randomized treatment assignment).
Defined as achieving a best overall response of confirmed complete response (CR) or confirmed partial response (PR).
Outcome measures
| Measure |
Tuc+Cap+Tra
n=273 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=137 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR
|
40.7 percentage of participants
Interval 34.8 to 46.7
|
23.4 percentage of participants
Interval 16.6 to 31.3
|
SECONDARY outcome
Timeframe: 34.6 monthsPopulation: ITT - PFS population, subset of participants with measurable disease by investigator at baseline. The ITT-PFS Population includes the first 480 randomized participants in the ITT analysis population (evaluated by their randomized treatment assignment).
Defined as achieving a best overall response of confirmed CR or confirmed PR.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=280 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=139 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
ORR Per RECIST 1.1 as Determined by Investigator Assessment
|
41.4 percentage of participants
Interval 35.6 to 47.4
|
23.0 percentage of participants
Interval 16.3 to 30.9
|
SECONDARY outcome
Timeframe: 34.6 monthsPopulation: ITT-PFS Population: Includes the first 480 randomized participants in the ITT analysis population (evaluated by their randomized treatment assignment).
Defined as the time from the date of randomization to the date of documented disease progression
Outcome measures
| Measure |
Tuc+Cap+Tra
n=320 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=160 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Primary Analysis
|
7.5 months
Interval 4.1 to 13.1
|
4.3 months
Interval 2.7 to 8.4
|
SECONDARY outcome
Timeframe: 24.6 monthsPopulation: ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR
|
8.3 months
Interval 4.3 to 12.8
|
6.3 months
Interval 4.2 to 9.0
|
SECONDARY outcome
Timeframe: 33.2 monthsPopulation: ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
DOR Per RECIST 1.1 as Determined by Investigator Assessment
|
7.0 months
Interval 4.3 to 12.9
|
6.9 months
Interval 4.1 to 9.6
|
SECONDARY outcome
Timeframe: 34.6 monthsPopulation: ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Clinical benefit was defined as achieving stable disease (SD) or non-complete response (CR)/non-progressive disease (PD) for at least 6 months or a best overall response of confirmed CR or confirmed partial response (PR).
Outcome measures
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1
|
59.8 percentage of participants
Interval 54.8 to 64.5
|
38.1 percentage of participants
Interval 31.4 to 45.2
|
SECONDARY outcome
Timeframe: 34.6 monthsPopulation: ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Clinical benefit was defined as achieving stable disease (SD) or non-CR/non-PD for at least 6 months or a best overall response of confirmed CR or confirmed PR.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
CBR Per RECIST 1.1 as Determined by Investigator Assessment
|
58.0 percentage of participants
Interval 53.1 to 62.9
|
37.6 percentage of participants
Interval 30.9 to 44.7
|
SECONDARY outcome
Timeframe: 36.1 monthsPopulation: Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
As determined by assessment of AEs, clinical laboratory tests, and vital signs measurements. AEs were classified by system organ class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22.0 or higher; AE severities were classified using Version 4.03 of the (Common Terminology Criteria for Adverse Events) CTCAE criteria.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=404 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=197 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Incidence of Adverse Events (AEs) at Time of Primary Analysis
Any treatment-emergent serious AE
|
104 Participants
|
53 Participants
|
|
Incidence of Adverse Events (AEs) at Time of Primary Analysis
Any treatment-emergent AE (TEAE)
|
401 Participants
|
191 Participants
|
|
Incidence of Adverse Events (AEs) at Time of Primary Analysis
Any Grade 3 or higher TEAE
|
223 Participants
|
96 Participants
|
|
Incidence of Adverse Events (AEs) at Time of Primary Analysis
TEAE leading to death
|
8 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 35.1 monthsPopulation: Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=404 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=197 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Frequency of Dose Modifications
TEAEs resulting in tuc/pbo dose modification
|
220 Participants
|
81 Participants
|
|
Frequency of Dose Modifications
TEAEs resulting in capecitabine dose reduction
|
243 Participants
|
77 Participants
|
|
Frequency of Dose Modifications
TEAEs resulting in tucatinib/placebo dose hold
|
216 Participants
|
80 Participants
|
|
Frequency of Dose Modifications
TEAEs resulting in tuc/pbo dose reduction
|
84 Participants
|
21 Participants
|
|
Frequency of Dose Modifications
TEAEs resulting capecitabine dose modification
|
313 Participants
|
122 Participants
|
|
Frequency of Dose Modifications
TEAEs resulting in capecitabine dose hold
|
276 Participants
|
113 Participants
|
|
Frequency of Dose Modifications
TEAEs resulting trastuzumab dose modification
|
104 Participants
|
38 Participants
|
|
Frequency of Dose Modifications
TEAEs resulting in trastuzumab dose hold
|
104 Participants
|
38 Participants
|
SECONDARY outcome
Timeframe: 36.1 monthsPopulation: Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
Cumulative incidence of health resource utilization, including length of stay, hospitalizations, and ER visits using the EQ-5D-5L questionnaire.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=404 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=197 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Incidence of Health Resources Utilization
Total number of hospitalizations
|
143 hospitalizations
|
75 hospitalizations
|
|
Incidence of Health Resources Utilization
Hospitalization for AE
|
124 hospitalizations
|
64 hospitalizations
|
|
Incidence of Health Resources Utilization
Planned hospitalization (other than AE)
|
10 hospitalizations
|
6 hospitalizations
|
|
Incidence of Health Resources Utilization
Ambulatory Surgery
|
3 hospitalizations
|
0 hospitalizations
|
|
Incidence of Health Resources Utilization
Other
|
6 hospitalizations
|
5 hospitalizations
|
SECONDARY outcome
Timeframe: 3.5 monthsPopulation: Pharmacokinetics (PK) Analysis Set: Includes all randomized participants who received at least one dose of tucatinib and who had at least one evaluable PK assessment. Participants were evaluated by the treatment actually received.
Individual plasma tucatinib concentrations at each sampling time
Outcome measures
| Measure |
Tuc+Cap+Tra
n=373 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Pharmacokinetic Measure: Ctrough of Tucatinib
Cycle 2, Day 1 (Pre-dose)
|
246.1 ng/mL
Standard Deviation 260.9
|
—
|
|
Pharmacokinetic Measure: Ctrough of Tucatinib
Cycle 3, Day 1 (Pre-dose)
|
227.6 ng/mL
Standard Deviation 210.8
|
—
|
|
Pharmacokinetic Measure: Ctrough of Tucatinib
Cycle 3, Day 1 (Post-dose)
|
507.1 ng/mL
Standard Deviation 357.1
|
—
|
|
Pharmacokinetic Measure: Ctrough of Tucatinib
Cycle 4, Day 1 (Pre-dose)
|
253.2 ng/mL
Standard Deviation 236.1
|
—
|
|
Pharmacokinetic Measure: Ctrough of Tucatinib
Cycle 5, Day 1 (Pre-dose)
|
257.6 ng/mL
Standard Deviation 286.9
|
—
|
|
Pharmacokinetic Measure: Ctrough of Tucatinib
Cycle 6, Day 1 (Pre-dose)
|
247.8 ng/mL
Standard Deviation 225.1
|
—
|
SECONDARY outcome
Timeframe: 3.5 monthsPopulation: PK Analysis Set: Includes all randomized participants who received at least one dose of tucatinib and who had at least one evaluable PK assessment. Participants were evaluated by the treatment actually received.
Individual plasma primary metabolite concentrations at each sampling time
Outcome measures
| Measure |
Tuc+Cap+Tra
n=373 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Pharmacokinetic Measure: ONT-993
Cycle 2, Day 1 (Pre-dose)
|
25.5 ng/mL
Standard Deviation 24.4
|
—
|
|
Pharmacokinetic Measure: ONT-993
Cycle 3, Day 1 (Pre-dose)
|
22.6 ng/mL
Standard Deviation 20.6
|
—
|
|
Pharmacokinetic Measure: ONT-993
Cycle 3, Day 1 (Post-dose)
|
47.7 ng/mL
Standard Deviation 47.2
|
—
|
|
Pharmacokinetic Measure: ONT-993
Cycle 4, Day 1 (Pre-dose)
|
25.2 ng/mL
Standard Deviation 24.3
|
—
|
|
Pharmacokinetic Measure: ONT-993
Cycle 5, Day 1 (Pre-dose)
|
24.5 ng/mL
Standard Deviation 30.6
|
—
|
|
Pharmacokinetic Measure: ONT-993
Cycle 6, Day 1 (Pre-dose)
|
20.9 ng/mL
Standard Deviation 18.0
|
—
|
SECONDARY outcome
Timeframe: Up to 60.1 monthsPopulation: ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Defined as time from randomization to death from any cause
Outcome measures
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Overall Survival (OS) at Time of Final Analysis
|
24.7 months
Interval 21.6 to 28.9
|
19.2 months
Interval 16.4 to 21.4
|
SECONDARY outcome
Timeframe: Up to 58.0 monthsPopulation: ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Defined as the time from the date of randomization to the date of documented disease progression
Outcome measures
| Measure |
Tuc+Cap+Tra
n=410 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=202 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Final Analysis
|
7.6 months
Interval 4.1 to 13.8
|
4.9 months
Interval 2.7 to 9.0
|
SECONDARY outcome
Timeframe: Up to 60.1 monthsPopulation: Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
As determined by assessment of AEs, clinical laboratory tests, and vital signs measurements. AEs were classified by system organ class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22.0 or higher; AE severities were classified using Version 4.03 of the (Common Terminology Criteria for Adverse Events) CTCAE criteria.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=404 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=197 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Incidence of Adverse Events (AEs) at Time of Final Analysis
Any Grade 3 or higher TEAE
|
248 Participants
|
101 Participants
|
|
Incidence of Adverse Events (AEs) at Time of Final Analysis
Any treatment-emergent serious AE
|
123 Participants
|
58 Participants
|
|
Incidence of Adverse Events (AEs) at Time of Final Analysis
Any treatment-emergent AE (TEAE)
|
401 Participants
|
191 Participants
|
|
Incidence of Adverse Events (AEs) at Time of Final Analysis
TEAE leading to death
|
8 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to 60.1 monthsPopulation: Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
Outcome measures
| Measure |
Tuc+Cap+Tra
n=404 Participants
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=197 Participants
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting in trastuzumab dose hold
|
117 Participants
|
41 Participants
|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting trastuzumab dose modification
|
117 Participants
|
41 Participants
|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting in tuc/pbo dose modification
|
237 Participants
|
85 Participants
|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting in tucatinib/placebo dose hold
|
232 Participants
|
84 Participants
|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting in tuc/pbo dose reduction
|
92 Participants
|
21 Participants
|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting capecitabine dose modification
|
322 Participants
|
125 Participants
|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting in capecitabine dose hold
|
288 Participants
|
117 Participants
|
|
Frequency of Dose Modifications at Time of Final Analysis
TEAEs resulting in capecitabine dose reduction
|
251 Participants
|
79 Participants
|
Adverse Events
Tuc+Cap+Tra
Serious events: 124 serious events
Other events: 399 other events
Deaths: 262 deaths
Pbo+Cap+Tra
Serious events: 62 serious events
Other events: 188 other events
Deaths: 152 deaths
Serious adverse events
| Measure |
Tuc+Cap+Tra
n=404 participants at risk
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=197 participants at risk
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Cardiac arrest
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Cardiac failure
|
0.74%
3/404 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Cardiac failure acute
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Cardiovascular disorder
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Pericardial effusion
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Ear and labyrinth disorders
Vestibular disorder
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Eye disorders
Diplopia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Eye disorders
Optic neuropathy
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Abdominal distension
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.99%
4/404 • Number of events 4 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.74%
3/404 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Constipation
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Diarrhoea
|
4.2%
17/404 • Number of events 18 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.6%
7/197 • Number of events 8 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Gastritis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Mechanical ileus
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Nausea
|
2.2%
9/404 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
2.0%
4/197 • Number of events 4 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Stomatitis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Vomiting
|
2.7%
11/404 • Number of events 12 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
2.5%
5/197 • Number of events 5 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Fatigue
|
0.74%
3/404 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
General physical health deterioration
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Non-cardiac chest pain
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Oedema peripheral
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Pain
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Pyrexia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Sudden death
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Systemic inflammatory response syndrome
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Hepatobiliary disorders
Biliary obstruction
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.74%
3/404 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Anal abscess
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Bacteraemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Cellulitis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Clostridium difficile colitis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Diverticulitis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Gastroenteritis
|
0.74%
3/404 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Infected skin ulcer
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Influenza
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Large intestine infection
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Lower respiratory tract infection viral
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Oesophageal candidiasis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Oral candidiasis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Peritonitis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Pneumonia
|
2.0%
8/404 • Number of events 9 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.5%
3/197 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Sepsis
|
0.99%
4/404 • Number of events 4 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Septic shock
|
0.25%
1/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Soft tissue infection
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Urinary tract infection
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Urosepsis
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Sternal fracture
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Blood bilirubin increased
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Ejection fraction decreased
|
1.5%
6/404 • Number of events 6 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.5%
3/197 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Troponin I increased
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
White blood cell count decreased
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.99%
4/404 • Number of events 4 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.25%
1/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
2.0%
4/197 • Number of events 4 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Lactic acidosis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.74%
3/404 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Fracture nonunion
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc compression
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.74%
3/404 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Spinal stenosis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acral lentiginous melanoma
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pyogenic granuloma
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Aphasia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Bell's palsy
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Brain oedema
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Cauda equina syndrome
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Central nervous system necrosis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Depressed level of consciousness
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Encephalopathy
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Epilepsy
|
0.25%
1/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.25%
1/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Headache
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.5%
3/197 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Hemiparesis
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Hydrocephalus
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Seizure
|
2.7%
11/404 • Number of events 11 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Spinal cord compression
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Syncope
|
0.74%
3/404 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Psychiatric disorders
Confusional state
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Psychiatric disorders
Mental status changes
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Renal and urinary disorders
Acute kidney injury
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Renal and urinary disorders
Ureterolithiasis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Renal and urinary disorders
Urinary retention
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
0.25%
1/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.5%
6/404 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.6%
7/197 • Number of events 8 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.0%
2/197 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.74%
3/404 • Number of events 5 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.99%
4/404 • Number of events 4 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.5%
3/197 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Skin and subcutaneous tissue disorders
Dermatomyositis
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Surgical and medical procedures
Abortion induced
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Vascular disorders
Hypotension
|
0.50%
2/404 • Number of events 2 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Vascular disorders
Lymphoedema
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Vascular disorders
Orthostatic hypotension
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Vascular disorders
Vena cava thrombosis
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Cardiac disorders
Cardiac Failure Congestive
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Traumatic haemothorax
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.00%
0/404 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.51%
1/197 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Hemiplegia
|
0.25%
1/404 • Number of events 1 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
0.00%
0/197 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
Other adverse events
| Measure |
Tuc+Cap+Tra
n=404 participants at risk
Tucatinib in combination with capecitabine \& trastuzumab
|
Pbo+Cap+Tra
n=197 participants at risk
Placebo in combination with capecitabine \& trastuzumab
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
22.0%
89/404 • Number of events 146 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
12.2%
24/197 • Number of events 32 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
9.2%
37/404 • Number of events 87 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
8.6%
17/197 • Number of events 40 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.7%
27/404 • Number of events 41 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.6%
11/197 • Number of events 15 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Eye disorders
Dry eye
|
5.7%
23/404 • Number of events 25 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Abdominal distension
|
6.7%
27/404 • Number of events 30 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 13 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Abdominal pain
|
16.3%
66/404 • Number of events 98 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
16.2%
32/197 • Number of events 40 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.9%
36/404 • Number of events 43 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
8.6%
17/197 • Number of events 20 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Constipation
|
17.1%
69/404 • Number of events 90 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
20.3%
40/197 • Number of events 46 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Diarrhoea
|
81.7%
330/404 • Number of events 812 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
53.8%
106/197 • Number of events 181 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Dry mouth
|
5.4%
22/404 • Number of events 22 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
2.5%
5/197 • Number of events 5 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Dyspepsia
|
11.4%
46/404 • Number of events 53 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
9.6%
19/197 • Number of events 22 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.2%
25/404 • Number of events 27 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.6%
7/197 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Nausea
|
60.1%
243/404 • Number of events 382 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
44.2%
87/197 • Number of events 120 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Stomatitis
|
26.0%
105/404 • Number of events 146 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
14.2%
28/197 • Number of events 35 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Gastrointestinal disorders
Vomiting
|
38.4%
155/404 • Number of events 276 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
24.9%
49/197 • Number of events 80 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Asthenia
|
8.4%
34/404 • Number of events 46 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
7.6%
15/197 • Number of events 19 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Fatigue
|
47.8%
193/404 • Number of events 265 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
44.2%
87/197 • Number of events 108 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Influenza like illness
|
5.9%
24/404 • Number of events 31 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 6 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Oedema peripheral
|
11.4%
46/404 • Number of events 52 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
9.6%
19/197 • Number of events 25 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
General disorders
Pyrexia
|
6.2%
25/404 • Number of events 35 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
4.1%
8/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
7.2%
29/404 • Number of events 69 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
4.1%
8/197 • Number of events 17 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Influenza
|
2.5%
10/404 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Nasopharyngitis
|
5.2%
21/404 • Number of events 28 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
7.1%
14/197 • Number of events 15 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Paronychia
|
5.7%
23/404 • Number of events 30 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.5%
3/197 • Number of events 4 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Upper respiratory tract infection
|
11.1%
45/404 • Number of events 70 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
7.6%
15/197 • Number of events 18 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Infections and infestations
Urinary tract infection
|
11.1%
45/404 • Number of events 76 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
8.1%
16/197 • Number of events 24 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Injury, poisoning and procedural complications
Fall
|
6.9%
28/404 • Number of events 41 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
4.6%
9/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Alanine aminotransferase increased
|
21.5%
87/404 • Number of events 115 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
6.6%
13/197 • Number of events 15 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Aspartate aminotransferase increased
|
22.8%
92/404 • Number of events 137 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
11.7%
23/197 • Number of events 32 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Blood alkaline phosphatase increased
|
7.2%
29/404 • Number of events 47 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 8 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Blood bilirubin increased
|
20.0%
81/404 • Number of events 154 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
10.7%
21/197 • Number of events 31 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Blood creatinine increased
|
16.1%
65/404 • Number of events 108 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.5%
3/197 • Number of events 3 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Neutrophil count decreased
|
5.2%
21/404 • Number of events 48 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Platelet count decreased
|
5.4%
22/404 • Number of events 29 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
2.5%
5/197 • Number of events 6 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
Weight decreased
|
15.3%
62/404 • Number of events 66 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
6.1%
12/197 • Number of events 13 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Investigations
White blood cell count decreased
|
5.2%
21/404 • Number of events 57 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
26.7%
108/404 • Number of events 130 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
20.8%
41/197 • Number of events 51 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Dehydration
|
7.7%
31/404 • Number of events 40 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 13 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.4%
26/404 • Number of events 40 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
1.5%
3/197 • Number of events 5 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
17.6%
71/404 • Number of events 105 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
12.2%
24/197 • Number of events 32 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
9.2%
37/404 • Number of events 61 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.2%
29/404 • Number of events 50 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.8%
80/404 • Number of events 120 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
8.6%
17/197 • Number of events 25 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.4%
58/404 • Number of events 73 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
12.7%
25/197 • Number of events 27 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
11.4%
46/404 • Number of events 63 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.4%
22/404 • Number of events 25 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.4%
34/404 • Number of events 43 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 11 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.6%
51/404 • Number of events 66 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
9.1%
18/197 • Number of events 22 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Dizziness
|
13.4%
54/404 • Number of events 68 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
13.7%
27/197 • Number of events 30 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Dysgeusia
|
8.2%
33/404 • Number of events 33 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 6 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Headache
|
24.3%
98/404 • Number of events 150 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
19.3%
38/197 • Number of events 53 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Paraesthesia
|
6.4%
26/404 • Number of events 32 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
13.1%
53/404 • Number of events 65 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
6.6%
13/197 • Number of events 17 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Psychiatric disorders
Insomnia
|
9.9%
40/404 • Number of events 45 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
8.6%
17/197 • Number of events 18 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.6%
67/404 • Number of events 85 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
12.2%
24/197 • Number of events 31 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.1%
53/404 • Number of events 60 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
11.7%
23/197 • Number of events 27 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.9%
52/404 • Number of events 63 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 10 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.7%
31/404 • Number of events 37 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
4.6%
9/197 • Number of events 14 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.9%
28/404 • Number of events 32 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.0%
6/197 • Number of events 6 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.2%
25/404 • Number of events 26 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
3.6%
7/197 • Number of events 7 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.6%
43/404 • Number of events 53 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
9.1%
18/197 • Number of events 20 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
65.6%
265/404 • Number of events 433 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
53.3%
105/197 • Number of events 158 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.7%
39/404 • Number of events 48 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
7.6%
15/197 • Number of events 15 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
7.2%
29/404 • Number of events 43 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 13 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
8.4%
34/404 • Number of events 45 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.6%
11/197 • Number of events 11 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
|
Vascular disorders
Hypertension
|
4.7%
19/404 • Number of events 30 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
5.1%
10/197 • Number of events 14 • Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 60.1 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place