Trial Outcomes & Findings for Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors (NCT NCT03375320)
NCT ID: NCT03375320
Last Updated: 2025-11-12
Results Overview
Will be assessed per Response Evaluation Criteria in Solid Tumors 1.1 determined by retrospective independent central review. Will be compared between treatment arms using the stratified log rank test at one-sided level 0.025. The stratification factors will be used for the analysis. The hazard ratio (HR) for PFS will be estimated using a stratified Cox proportional hazards model, and the 95% confidence interval (CI) for the HR will be provided. Results from an unstratified analysis will also be provided. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm, and Kaplan-Meier curves will be produced. Brookmeyer Crowley methodology will be used to construct the 95% CI for the median PFS for each treatment arm.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE3
Target enrollment
298 participants
Primary outcome timeframe
36 months
Results posted on
2025-11-12
Participant Flow
Participant milestones
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.\>
\> Cabozantinib S-malate: Given PO\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.\>
\> Cabozantinib S-malate: Given PO\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
134
|
69
|
64
|
31
|
|
Overall Study
Initiated Treatment
|
132
|
67
|
63
|
31
|
|
Overall Study
COMPLETED
|
21
|
7
|
14
|
2
|
|
Overall Study
NOT COMPLETED
|
113
|
62
|
50
|
29
|
Reasons for withdrawal
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.\>
\> Cabozantinib S-malate: Given PO\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.\>
\> Cabozantinib S-malate: Given PO\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
34
|
9
|
10
|
0
|
|
Overall Study
Death
|
6
|
3
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
7
|
4
|
5
|
4
|
|
Overall Study
Progressive disease
|
55
|
41
|
29
|
24
|
|
Overall Study
Alternative treatment
|
6
|
1
|
1
|
0
|
|
Overall Study
Other disease
|
1
|
1
|
3
|
0
|
|
Overall Study
Withdrawal prior to initiation
|
2
|
2
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
1
|
1
|
1
|
|
Overall Study
Non-compliance
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors
Baseline characteristics by cohort
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
n=134 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.\>
\> Cabozantinib S-malate: Given PO\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
n=69 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
n=64 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.\>
\> Cabozantinib S-malate: Given PO\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
n=31 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.\>
\> Computed Tomography: Undergo CT\>
\> Magnetic Resonance Imaging: Undergo MRI\>
\> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> X-Ray Imaging: Undergo x-ray
|
Total
n=298 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
66 years
n=10 Participants
|
66 years
n=10 Participants
|
59.5 years
n=20 Participants
|
64 years
n=45 Participants
|
66 years
n=44 Participants
|
|
Sex: Female, Male
Female
|
74 Participants
n=10 Participants
|
31 Participants
n=10 Participants
|
27 Participants
n=20 Participants
|
13 Participants
n=45 Participants
|
145 Participants
n=44 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=10 Participants
|
38 Participants
n=10 Participants
|
37 Participants
n=20 Participants
|
18 Participants
n=45 Participants
|
153 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=10 Participants
|
9 Participants
n=10 Participants
|
2 Participants
n=20 Participants
|
2 Participants
n=45 Participants
|
21 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
125 Participants
n=10 Participants
|
56 Participants
n=10 Participants
|
61 Participants
n=20 Participants
|
26 Participants
n=45 Participants
|
268 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=10 Participants
|
4 Participants
n=10 Participants
|
1 Participants
n=20 Participants
|
3 Participants
n=45 Participants
|
9 Participants
n=44 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
1 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=10 Participants
|
1 Participants
n=10 Participants
|
4 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
8 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
1 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=10 Participants
|
7 Participants
n=10 Participants
|
3 Participants
n=20 Participants
|
3 Participants
n=45 Participants
|
22 Participants
n=44 Participants
|
|
Race (NIH/OMB)
White
|
115 Participants
n=10 Participants
|
55 Participants
n=10 Participants
|
54 Participants
n=20 Participants
|
25 Participants
n=45 Participants
|
249 Participants
n=44 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
1 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=10 Participants
|
6 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
3 Participants
n=45 Participants
|
16 Participants
n=44 Participants
|
|
Region of Enrollment
United States
|
134 participants
n=10 Participants
|
69 participants
n=10 Participants
|
64 participants
n=20 Participants
|
31 participants
n=45 Participants
|
298 participants
n=44 Participants
|
PRIMARY outcome
Timeframe: 36 monthsWill be assessed per Response Evaluation Criteria in Solid Tumors 1.1 determined by retrospective independent central review. Will be compared between treatment arms using the stratified log rank test at one-sided level 0.025. The stratification factors will be used for the analysis. The hazard ratio (HR) for PFS will be estimated using a stratified Cox proportional hazards model, and the 95% confidence interval (CI) for the HR will be provided. Results from an unstratified analysis will also be provided. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm, and Kaplan-Meier curves will be produced. Brookmeyer Crowley methodology will be used to construct the 95% CI for the median PFS for each treatment arm.
Outcome measures
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
n=134 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
n=69 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
n=64 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
n=31 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Progression-free Survival (PFS)
|
8.4 months
Interval 7.6 to 12.7
|
3.9 months
Interval 3.0 to 5.7
|
13.8 months
Interval 9.2 to 18.5
|
4.4 months
Interval 3.0 to 5.9
|
SECONDARY outcome
Timeframe: 60 monthsThe analyses for OS will follow intent-to-treat (ITT) principle and will be conducted separately within each cohort (pancreatic neuroendocrine tumor \[NET\] and carcinoid tumor). The distribution of OS will be estimated using the method of Kaplan-Meier. The median OS, along with the 95% CI, will be estimated by the two treatment groups. Overall survival will be compared between treatment arms using the stratified log-rank test at a one-sided cumulative 2.5% level of significance. The stratified Cox regression will be used to estimate the HR of OS, along with the 95% CI. A hierarchical approach will be used to control for family-wise type-I error rate, therefore OS will be formally statistically tested only if the primary efficacy endpoint, PFS, is statistically significantly different between the two treatment groups.
Outcome measures
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
n=134 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
n=69 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
n=64 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
n=31 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Overall Survival (OS)
|
21.9 months
Interval 18.8 to 30.4
|
19.7 months
Interval 14.2 to 30.0
|
40.0 months
Interval 31.3 to
Upper end of the confidence interval is not able to be estimated due to a low number of events
|
31.1 months
Interval 23.4 to
Upper end of the confidence interval is not able to be estimated due to a low number of events
|
SECONDARY outcome
Timeframe: 60 monthsFor CTCAE data, the frequency tables will be reviewed to determine the patterns. The overall adverse event rates will be compared between treatment groups using Chi-square test (or Fisher's exact test if the data in contingency table is sparse). PRO-CTCAE data will, at minimum, be analyzed similarly to CTCAE data. The initial analysis of each PRO-CTCAE item will use all available scores in an analysis which mirrors the approach used for the CTCAE data. Supplemental analysis will use model-based multiple imputation incorporating baseline patient characteristics and physician-rated performance status. CTCAE data may be incorporated as auxiliary data into multiple imputation models for AEs which are captured by both PRO-CTCAE and CTCAE. Results from supplemental analysis will be descriptively compared to the results of the initial analysis to assess the robustness of results to missing data. Additional analyses of PRO-CTCAE data beyond those specified above may be undertaken.
Outcome measures
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
n=134 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
n=69 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
n=64 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
n=31 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Number of Patients Experiencing Grade 3+ Adverse Events (AEs) Graded According to the Common Terminology Criteria for Adverse Events (CTCAE) and Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
|
104 Participants
|
47 Participants
|
49 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: 36 monthsWill be defined as the proportion of patients in each arm whose best response is either complete response (CR) or partial response (PR). Radiographic response rate for both cohorts: the analyses for confirmed radiographic response rate will follow the ITT principle and will be conducted separately within each cohort (pancreatic NET and carcinoid tumor). The proportion of patients with either confirmed CR or confirmed PR as their best response will be estimated using point estimates and 95% confidence intervals. Radiographic response rate will be compared between treatment arms using the 2-sample z-test to compare sample proportion at a one-sided 2.5% level of significance.
Outcome measures
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
n=134 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
n=69 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
n=64 Participants
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study.
\>
\> Cabozantinib S-malate: Given PO
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
n=31 Participants
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression.
\>
\> Computed Tomography: Undergo CT
\>
\> Magnetic Resonance Imaging: Undergo MRI
\>
\> Placebo Administration: Given PO
\>
\> Quality-of-Life Assessment: Ancillary studies
\>
\> X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Radiographic Response Rate
|
7 Participants
|
0 Participants
|
12 Participants
|
0 Participants
|
Adverse Events
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
Serious events: 89 serious events
Other events: 134 other events
Deaths: 60 deaths
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
Serious events: 41 serious events
Other events: 69 other events
Deaths: 37 deaths
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
Serious events: 49 serious events
Other events: 64 other events
Deaths: 21 deaths
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
Serious events: 21 serious events
Other events: 31 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
n=134 participants at risk
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. \>
* Cabozantinib S-malate: Given PO \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
n=69 participants at risk
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression. \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Placebo Administration: Given PO \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
n=64 participants at risk
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. \>
* Cabozantinib S-malate: Given PO \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
n=31 participants at risk
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression. \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Placebo Administration: Given PO \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/134 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
7.8%
5/64 • Number of events 5 • 60 months
|
9.7%
3/31 • Number of events 3 • 60 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Endocrine disorders
Hyperparathyroidism
|
0.75%
1/134 • Number of events 19 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Psychiatric disorders
Delirium
|
0.00%
0/134 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Diarrhea
|
11.2%
15/134 • Number of events 15 • 60 months
|
7.2%
5/69 • Number of events 5 • 60 months
|
6.2%
4/64 • Number of events 4 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Disease progression
|
0.75%
1/134 • Number of events 1 • 60 months
|
4.3%
3/69 • Number of events 3 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Duodenal perforation
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.5%
2/134 • Number of events 2 • 60 months
|
5.8%
4/69 • Number of events 4 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Edema limbs
|
0.75%
1/134 • Number of events 1 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Ejection fraction decreased
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Electrocardiogram T wave abnormal
|
1.5%
2/134 • Number of events 14 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Blood and lymphatic system disorders
Eosinophilia
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 4 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Esophageal hemorrhage
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Esophagitis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Surgical and medical procedures
Exploratory laparotomy; enterectomy with anastomosis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Hypertension
|
22.4%
30/134 • Number of events 30 • 60 months
|
7.2%
5/69 • Number of events 5 • 60 months
|
25.0%
16/64 • Number of events 16 • 60 months
|
25.8%
8/31 • Number of events 8 • 60 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Fatigue
|
11.2%
15/134 • Number of events 15 • 60 months
|
10.1%
7/69 • Number of events 7 • 60 months
|
15.6%
10/64 • Number of events 10 • 60 months
|
12.9%
4/31 • Number of events 4 • 60 months
|
|
General disorders
Fever
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/134 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Flushing
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Injury, poisoning and procedural complications
Fracture
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 9 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Gastroparesis
|
0.75%
1/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Investigations
GGT increased
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Glucose intolerance
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 7 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Headache
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Hepatobiliary disorders
Hepatic encephalopathy
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Hepatobiliary disorders
Hepatic pain
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 4 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Hypotension
|
1.5%
2/134 • Number of events 2 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.75%
1/134 • Number of events 1 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
6.2%
4/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
Hepatobiliary disorders
Intrahepatic biliary dilation
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Ischemia cerebrovascular
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Kidney infection
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Large Bowel Perforation
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Investigations
Lipase increased
|
0.75%
1/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Lung infection
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Investigations
Lymphocyte count decreased
|
9.7%
13/134 • Number of events 13 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Malaise
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
MRSE
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Mucositis oral
|
3.0%
4/134 • Number of events 4 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
7.8%
5/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Multi-organ failure
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Myocardial infarction
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Nausea
|
2.2%
3/134 • Number of events 3 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
7.8%
5/64 • Number of events 5 • 60 months
|
6.5%
2/31 • Number of events 2 • 60 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine cancer
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Neutrophil count decreased
|
3.0%
4/134 • Number of events 4 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
3.2%
1/31 • Number of events 12 • 60 months
|
|
General disorders
Pain
|
2.2%
3/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.2%
3/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrm
|
2.2%
3/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
7.8%
5/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Pericardial effusion
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Platelet count decreased
|
2.2%
3/134 • Number of events 3 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Hepatobiliary disorders
Portal hypertension
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 7 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Reversbl posterior leukoenceph syndrome
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Right foot drop
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Salmonella Gastroenteritis
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Seizure
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Sepsis
|
2.2%
3/134 • Number of events 3 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Severe LAD occlusion
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnea
|
0.75%
1/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.5%
2/134 • Number of events 4 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
9.7%
3/31 • Number of events 5 • 60 months
|
|
Infections and infestations
Soft tissue infection
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Spontaneous bacterial peritonitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Strangulated inguinal hernia
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Stroke
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Subendocardial ischemia
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Sudden death NOS
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Syncope
|
3.7%
5/134 • Number of events 6 • 60 months
|
5.8%
4/69 • Number of events 4 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Thromboembolic event
|
1.5%
2/134 • Number of events 2 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
12.5%
8/64 • Number of events 8 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Tooth Extraction
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Infections and infestations
Tooth infection
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Transient ischemic attacks
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Ureter Perforation
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 4 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Urinary tract infection
|
2.2%
3/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Vomiting
|
3.0%
4/134 • Number of events 4 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
6.2%
4/64 • Number of events 4 • 60 months
|
6.5%
2/31 • Number of events 2 • 60 months
|
|
Investigations
Weight loss
|
4.5%
6/134 • Number of events 6 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Investigations
White blood cell decreased
|
3.7%
5/134 • Number of events 5 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Wound infection
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Abdominal distension
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
9/134 • Number of events 9 • 60 months
|
7.2%
5/69 • Number of events 5 • 60 months
|
6.2%
4/64 • Number of events 4 • 60 months
|
12.9%
4/31 • Number of events 4 • 60 months
|
|
Gastrointestinal disorders
Acute intestinal obstruction
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Acute kidney injury
|
0.75%
1/134 • Number of events 2 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
6.5%
2/31 • Number of events 2 • 60 months
|
|
Nervous system disorders
Acute Metabolic Encephalopathy
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Alanine aminotransferase increased
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
6.5%
2/31 • Number of events 2 • 60 months
|
|
Investigations
Alkaline phosphatase increased
|
3.7%
5/134 • Number of events 5 • 60 months
|
5.8%
4/69 • Number of events 4 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Alkalosis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Anal fissure
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Blood and lymphatic system disorders
Anemia
|
3.0%
4/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Anorexia
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Psychiatric disorders
Anxiety
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Arterial thromboembolism
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Ascites
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 4 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Aspartate aminotransferase increased
|
3.0%
4/134 • Number of events 4 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Cardiac disorders
Atrial defect
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.0%
4/134 • Number of events 4 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Bacteremia sepsis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Bloating
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Blood bilirubin increased
|
4.5%
6/134 • Number of events 6 • 60 months
|
4.3%
3/69 • Number of events 3 • 60 months
|
4.7%
3/64 • Number of events 3 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Cardiac arrest
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Cardiac disorders - Other, specify
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Cardiac troponin I increased
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Chest pain - cardiac
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
6.5%
2/31 • Number of events 2 • 60 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Chronic kidney disease
|
1.5%
2/134 • Number of events 2 • 60 months
|
1.4%
1/69 • Number of events 4 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Cognitive disturbance
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Colonic obstruction
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Psychiatric disorders
Confusion
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Constipation
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Surgical and medical procedures
Craniotomy
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Investigations
Creatinine increased
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Endocrine disorders
Cushing's Syndrome
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Death NOS
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/134 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
1.5%
2/134 • Number of events 2 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
Other adverse events
| Measure |
Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET])
n=134 participants at risk
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. \>
* Cabozantinib S-malate: Given PO \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET])
n=69 participants at risk
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression. \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Placebo Administration: Given PO \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
Arm Ib (Cabozantinib S-malate, Pancreatic NET Cohort [pNET])
n=64 participants at risk
Patients receive cabozantinib S-malate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. \>
* Cabozantinib S-malate: Given PO \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
Arm IIb (Placebo, Pancreatic NET Cohort [pNET])
n=31 participants at risk
Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or x-ray imaging during screening and on study. Patients may crossover to receive cabozantinib S-malate at the time of disease progression. \>
* Computed Tomography: Undergo CT \>
* Magnetic Resonance Imaging: Undergo MRI \>
* Placebo Administration: Given PO \>
* Quality-of-Life Assessment: Ancillary studies \>
* X-Ray Imaging: Undergo x-ray
|
|---|---|---|---|---|
|
Infections and infestations
Shingles
|
1.5%
2/134 • Number of events 10 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Cardiac disorders
Sinus bradycardia
|
6.0%
8/134 • Number of events 35 • 60 months
|
2.9%
2/69 • Number of events 6 • 60 months
|
4.7%
3/64 • Number of events 23 • 60 months
|
6.5%
2/31 • Number of events 5 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Sinus pain
|
0.75%
1/134 • Number of events 4 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Sinus tachycardia
|
6.7%
9/134 • Number of events 32 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Sinusitis
|
1.5%
2/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcut tissue disord - Oth spec
|
13.4%
18/134 • Number of events 141 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
9.4%
6/64 • Number of events 30 • 60 months
|
6.5%
2/31 • Number of events 5 • 60 months
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
0.75%
1/134 • Number of events 13 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 8 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Skin infection
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 10 • 60 months
|
0.00%
0/31 • 60 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
1.5%
2/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 3 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnea
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 6 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Somnolence
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
6.0%
8/134 • Number of events 37 • 60 months
|
2.9%
2/69 • Number of events 5 • 60 months
|
9.4%
6/64 • Number of events 20 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Stomach pain
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
1.6%
1/64 • Number of events 4 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Surgical and medical procedures
Surgical and medical proced - Oth spec
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Nervous system disorders
Syncope
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Telangiectasia
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 10 • 60 months
|
1.6%
1/64 • Number of events 3 • 60 months
|
0.00%
0/31 • 60 months
|
|
Reproductive system and breast disorders
Testicular disorder
|
0.75%
1/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Thromboembolic event
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
6.2%
4/64 • Number of events 41 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Infections and infestations
Thrush
|
3.0%
4/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 8 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Thyroid stimulating hormone increased
|
6.0%
8/134 • Number of events 41 • 60 months
|
2.9%
2/69 • Number of events 4 • 60 months
|
12.5%
8/64 • Number of events 65 • 60 months
|
0.00%
0/31 • 60 months
|
|
Ear and labyrinth disorders
Tinnitus
|
3.0%
4/134 • Number of events 23 • 60 months
|
5.8%
4/69 • Number of events 32 • 60 months
|
4.7%
3/64 • Number of events 49 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Tooth discoloration
|
0.75%
1/134 • Number of events 8 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Tooth infection
|
3.7%
5/134 • Number of events 8 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
3.1%
2/64 • Number of events 24 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Tremor
|
3.0%
4/134 • Number of events 12 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Tricuspid valve disease
|
0.75%
1/134 • Number of events 10 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
1.5%
2/134 • Number of events 20 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Upper respiratory infection
|
4.5%
6/134 • Number of events 7 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 4 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Urinary frequency
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
3.1%
2/64 • Number of events 8 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Urinary incontinence
|
1.5%
2/134 • Number of events 17 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Urinary tract infection
|
6.0%
8/134 • Number of events 25 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
7.8%
5/64 • Number of events 34 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Urinary urgency
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Urine discoloration
|
2.2%
3/134 • Number of events 5 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Reproductive system and breast disorders
Vaginal discharge
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Vascular disorders - Other, specify
|
1.5%
2/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.75%
1/134 • Number of events 18 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Ear and labyrinth disorders
Vertigo
|
1.5%
2/134 • Number of events 10 • 60 months
|
2.9%
2/69 • Number of events 4 • 60 months
|
1.6%
1/64 • Number of events 6 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Viremia
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Eye disorders
Vision decreased
|
1.5%
2/134 • Number of events 16 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Eye disorders
Vitreous hemorrhage
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
3.0%
4/134 • Number of events 24 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Vomiting
|
16.4%
22/134 • Number of events 70 • 60 months
|
7.2%
5/69 • Number of events 8 • 60 months
|
21.9%
14/64 • Number of events 29 • 60 months
|
9.7%
3/31 • Number of events 7 • 60 months
|
|
Eye disorders
Watering eyes
|
0.75%
1/134 • Number of events 9 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Weight gain
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Weight loss
|
26.1%
35/134 • Number of events 300 • 60 months
|
4.3%
3/69 • Number of events 4 • 60 months
|
15.6%
10/64 • Number of events 91 • 60 months
|
3.2%
1/31 • Number of events 12 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
White blood cell decreased
|
33.6%
45/134 • Number of events 311 • 60 months
|
2.9%
2/69 • Number of events 11 • 60 months
|
18.8%
12/64 • Number of events 59 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Injury, poisoning and procedural complications
Wound complication
|
2.2%
3/134 • Number of events 13 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 3 • 60 months
|
0.00%
0/31 • 60 months
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Dry mouth
|
15.7%
21/134 • Number of events 163 • 60 months
|
7.2%
5/69 • Number of events 24 • 60 months
|
4.7%
3/64 • Number of events 30 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.2%
11/134 • Number of events 111 • 60 months
|
4.3%
3/69 • Number of events 12 • 60 months
|
10.9%
7/64 • Number of events 26 • 60 months
|
6.5%
2/31 • Number of events 13 • 60 months
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Dysesthesia
|
3.0%
4/134 • Number of events 19 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Dysgeusia
|
36.6%
49/134 • Number of events 339 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
31.2%
20/64 • Number of events 153 • 60 months
|
6.5%
2/31 • Number of events 4 • 60 months
|
|
Gastrointestinal disorders
Dyspepsia
|
3.0%
4/134 • Number of events 11 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
4.7%
3/64 • Number of events 11 • 60 months
|
3.2%
1/31 • Number of events 3 • 60 months
|
|
Gastrointestinal disorders
Dysphagia
|
3.0%
4/134 • Number of events 8 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
15.7%
21/134 • Number of events 101 • 60 months
|
13.0%
9/69 • Number of events 21 • 60 months
|
18.8%
12/64 • Number of events 51 • 60 months
|
6.5%
2/31 • Number of events 5 • 60 months
|
|
Renal and urinary disorders
Dysuria (painful urination)
|
1.5%
2/134 • Number of events 10 • 60 months
|
4.3%
3/69 • Number of events 5 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders - Oth spec
|
3.0%
4/134 • Number of events 26 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Ear and labyrinth disorders
Ear pain
|
1.5%
2/134 • Number of events 2 • 60 months
|
2.9%
2/69 • Number of events 5 • 60 months
|
1.6%
1/64 • Number of events 3 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
ECG QT corrected interval prolonged
|
3.0%
4/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
4.7%
3/64 • Number of events 4 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Edema face
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
General disorders
Edema limbs
|
14.9%
20/134 • Number of events 135 • 60 months
|
7.2%
5/69 • Number of events 13 • 60 months
|
6.2%
4/64 • Number of events 12 • 60 months
|
9.7%
3/31 • Number of events 6 • 60 months
|
|
Endocrine disorders
Endocrine disorders - Other, specify
|
0.75%
1/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
4.7%
3/64 • Number of events 8 • 60 months
|
0.00%
0/31 • 60 months
|
|
Blood and lymphatic system disorders
Eosinophilia
|
1.5%
2/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
9.4%
6/64 • Number of events 27 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.7%
9/134 • Number of events 57 • 60 months
|
0.00%
0/69 • 60 months
|
6.2%
4/64 • Number of events 13 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Esophageal ulcer
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Esophagitis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Ear and labyrinth disorders
External ear pain
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Eye disorders
Eye disorders - Other, specify
|
6.0%
8/134 • Number of events 34 • 60 months
|
1.4%
1/69 • Number of events 5 • 60 months
|
1.6%
1/64 • Number of events 9 • 60 months
|
0.00%
0/31 • 60 months
|
|
Injury, poisoning and procedural complications
Fall
|
6.0%
8/134 • Number of events 13 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Fatigue
|
76.9%
103/134 • Number of events 951 • 60 months
|
60.9%
42/69 • Number of events 177 • 60 months
|
75.0%
48/64 • Number of events 492 • 60 months
|
54.8%
17/31 • Number of events 95 • 60 months
|
|
Gastrointestinal disorders
Fecal incontinence
|
1.5%
2/134 • Number of events 17 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Fever
|
3.0%
4/134 • Number of events 5 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
6.2%
4/64 • Number of events 26 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
3.0%
4/134 • Number of events 32 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
4.7%
3/64 • Number of events 31 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Flatulence
|
10.4%
14/134 • Number of events 103 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
6.2%
4/64 • Number of events 22 • 60 months
|
0.00%
0/31 • 60 months
|
|
Eye disorders
Floaters
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Flu like symptoms
|
2.2%
3/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
6.2%
4/64 • Number of events 8 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Flushing
|
11.9%
16/134 • Number of events 127 • 60 months
|
14.5%
10/69 • Number of events 60 • 60 months
|
7.8%
5/64 • Number of events 16 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Infections and infestations
Folliculitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Injury, poisoning and procedural complications
Fracture
|
2.2%
3/134 • Number of events 16 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Gait disturbance
|
2.2%
3/134 • Number of events 11 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Gastritis
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
14.9%
20/134 • Number of events 157 • 60 months
|
4.3%
3/69 • Number of events 9 • 60 months
|
15.6%
10/64 • Number of events 90 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Oth spec
|
6.0%
8/134 • Number of events 49 • 60 months
|
5.8%
4/69 • Number of events 11 • 60 months
|
9.4%
6/64 • Number of events 56 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
2.2%
3/134 • Number of events 19 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 13 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Gastroparesis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Gen disord and admin site conds-Oth spec
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 7 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Generalized edema
|
2.2%
3/134 • Number of events 15 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
9.7%
13/134 • Number of events 41 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Eye disorders
Glaucoma
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Gum infection
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Hair color changes
|
9.7%
13/134 • Number of events 110 • 60 months
|
0.00%
0/69 • 60 months
|
10.9%
7/64 • Number of events 74 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Hair texture abnormal
|
1.5%
2/134 • Number of events 18 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Headache
|
17.9%
24/134 • Number of events 102 • 60 months
|
13.0%
9/69 • Number of events 18 • 60 months
|
15.6%
10/64 • Number of events 75 • 60 months
|
6.5%
2/31 • Number of events 2 • 60 months
|
|
Ear and labyrinth disorders
Hearing impaired
|
3.0%
4/134 • Number of events 41 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 4 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Cardiac disorders
Heart failure
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Vascular disorders
Hematoma
|
2.2%
3/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Hematuria
|
1.5%
2/134 • Number of events 5 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Hemoglobin increased
|
2.2%
3/134 • Number of events 8 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
0.75%
1/134 • Number of events 8 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Hemorrhoids
|
3.7%
5/134 • Number of events 37 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
6.5%
2/31 • Number of events 3 • 60 months
|
|
Infections and infestations
Herpes simplex reactivation
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
1.5%
2/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
8.2%
11/134 • Number of events 74 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
10.9%
7/64 • Number of events 80 • 60 months
|
0.00%
0/31 • 60 months
|
|
Vascular disorders
Hot flashes
|
2.2%
3/134 • Number of events 21 • 60 months
|
4.3%
3/69 • Number of events 5 • 60 months
|
1.6%
1/64 • Number of events 20 • 60 months
|
6.5%
2/31 • Number of events 4 • 60 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.2%
3/134 • Number of events 6 • 60 months
|
7.2%
5/69 • Number of events 5 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
9.7%
3/31 • Number of events 4 • 60 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
37.3%
50/134 • Number of events 297 • 60 months
|
36.2%
25/69 • Number of events 128 • 60 months
|
40.6%
26/64 • Number of events 234 • 60 months
|
48.4%
15/31 • Number of events 61 • 60 months
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.2%
3/134 • Number of events 4 • 60 months
|
5.8%
4/69 • Number of events 17 • 60 months
|
1.6%
1/64 • Number of events 3 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
9.0%
12/134 • Number of events 37 • 60 months
|
8.7%
6/69 • Number of events 8 • 60 months
|
10.9%
7/64 • Number of events 23 • 60 months
|
9.7%
3/31 • Number of events 8 • 60 months
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
0.75%
1/134 • Number of events 7 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hyperlipidemia
|
3.0%
4/134 • Number of events 33 • 60 months
|
2.9%
2/69 • Number of events 4 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
4.5%
6/134 • Number of events 9 • 60 months
|
0.00%
0/69 • 60 months
|
4.7%
3/64 • Number of events 5 • 60 months
|
9.7%
3/31 • Number of events 15 • 60 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
1.5%
2/134 • Number of events 17 • 60 months
|
4.3%
3/69 • Number of events 7 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
2.2%
3/134 • Number of events 12 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Vascular disorders
Hypertension
|
48.5%
65/134 • Number of events 828 • 60 months
|
39.1%
27/69 • Number of events 148 • 60 months
|
48.4%
31/64 • Number of events 461 • 60 months
|
35.5%
11/31 • Number of events 69 • 60 months
|
|
Endocrine disorders
Hyperthyroidism
|
3.0%
4/134 • Number of events 7 • 60 months
|
0.00%
0/69 • 60 months
|
6.2%
4/64 • Number of events 13 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 21 • 60 months
|
1.6%
1/64 • Number of events 3 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
22.4%
30/134 • Number of events 118 • 60 months
|
7.2%
5/69 • Number of events 9 • 60 months
|
17.2%
11/64 • Number of events 48 • 60 months
|
12.9%
4/31 • Number of events 16 • 60 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
20.9%
28/134 • Number of events 92 • 60 months
|
5.8%
4/69 • Number of events 5 • 60 months
|
23.4%
15/64 • Number of events 50 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
6.7%
9/134 • Number of events 18 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
10.9%
7/64 • Number of events 10 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
19.4%
26/134 • Number of events 62 • 60 months
|
7.2%
5/69 • Number of events 21 • 60 months
|
9.4%
6/64 • Number of events 30 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
19.4%
26/134 • Number of events 149 • 60 months
|
2.9%
2/69 • Number of events 16 • 60 months
|
10.9%
7/64 • Number of events 50 • 60 months
|
6.5%
2/31 • Number of events 6 • 60 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
17.9%
24/134 • Number of events 76 • 60 months
|
5.8%
4/69 • Number of events 8 • 60 months
|
17.2%
11/64 • Number of events 41 • 60 months
|
16.1%
5/31 • Number of events 12 • 60 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
18.7%
25/134 • Number of events 71 • 60 months
|
5.8%
4/69 • Number of events 7 • 60 months
|
25.0%
16/64 • Number of events 69 • 60 months
|
6.5%
2/31 • Number of events 4 • 60 months
|
|
Vascular disorders
Hypotension
|
5.2%
7/134 • Number of events 17 • 60 months
|
0.00%
0/69 • 60 months
|
7.8%
5/64 • Number of events 13 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Endocrine disorders
Hypothyroidism
|
36.6%
49/134 • Number of events 385 • 60 months
|
7.2%
5/69 • Number of events 48 • 60 months
|
32.8%
21/64 • Number of events 242 • 60 months
|
9.7%
3/31 • Number of events 9 • 60 months
|
|
Infections and infestations
Infections and infestations - Oth spec
|
7.5%
10/134 • Number of events 12 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
9.4%
6/64 • Number of events 6 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Investigations
INR increased
|
2.2%
3/134 • Number of events 23 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Psychiatric disorders
Insomnia
|
8.2%
11/134 • Number of events 52 • 60 months
|
7.2%
5/69 • Number of events 15 • 60 months
|
6.2%
4/64 • Number of events 18 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Nervous system disorders
Intracranial hemorrhage
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Investigations - Other, specify
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
3.1%
2/64 • Number of events 5 • 60 months
|
3.2%
1/31 • Number of events 5 • 60 months
|
|
Infections and infestations
Joint infection
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal edema
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 18 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal hemorrhage
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
0.75%
1/134 • Number of events 8 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 6 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Nervous system disorders
Lethargy
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Lipase increased
|
0.00%
0/134 • 60 months
|
4.3%
3/69 • Number of events 6 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Localized edema
|
3.7%
5/134 • Number of events 23 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 24 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Lung infection
|
1.5%
2/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Blood and lymphatic system disorders
Lymph node pain
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Lymphocyte count decreased
|
20.1%
27/134 • Number of events 388 • 60 months
|
17.4%
12/69 • Number of events 43 • 60 months
|
18.8%
12/64 • Number of events 82 • 60 months
|
16.1%
5/31 • Number of events 9 • 60 months
|
|
Investigations
Lymphocyte count increased
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
4.7%
3/64 • Number of events 9 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Malabsorption
|
1.5%
2/134 • Number of events 7 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 3 • 60 months
|
|
General disorders
Malaise
|
1.5%
2/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Nervous system disorders
Memory impairment
|
2.2%
3/134 • Number of events 7 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
1.6%
1/64 • Number of events 22 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Metabolism, nutrition disord - Oth spec
|
0.75%
1/134 • Number of events 2 • 60 months
|
1.4%
1/69 • Number of events 38 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Mucositis oral
|
35.8%
48/134 • Number of events 239 • 60 months
|
8.7%
6/69 • Number of events 10 • 60 months
|
40.6%
26/64 • Number of events 174 • 60 months
|
6.5%
2/31 • Number of events 3 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Muscle cramp
|
13.4%
18/134 • Number of events 90 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
15.6%
10/64 • Number of events 48 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal, conn tissue - Oth spec
|
3.0%
4/134 • Number of events 32 • 60 months
|
2.9%
2/69 • Number of events 22 • 60 months
|
4.7%
3/64 • Number of events 44 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.0%
8/134 • Number of events 61 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
7.8%
5/64 • Number of events 37 • 60 months
|
6.5%
2/31 • Number of events 15 • 60 months
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
1.5%
2/134 • Number of events 12 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
6.2%
4/64 • Number of events 52 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
0.75%
1/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 3 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Nail infection
|
0.75%
1/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.7%
5/134 • Number of events 13 • 60 months
|
4.3%
3/69 • Number of events 4 • 60 months
|
1.6%
1/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Nausea
|
39.6%
53/134 • Number of events 281 • 60 months
|
18.8%
13/69 • Number of events 33 • 60 months
|
32.8%
21/64 • Number of events 126 • 60 months
|
25.8%
8/31 • Number of events 23 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.2%
3/134 • Number of events 8 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Nervous system disorders - Oth spec
|
2.2%
3/134 • Number of events 32 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Neuralgia
|
0.75%
1/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Neutrophil count decreased
|
36.6%
49/134 • Number of events 251 • 60 months
|
2.9%
2/69 • Number of events 4 • 60 months
|
26.6%
17/64 • Number of events 93 • 60 months
|
6.5%
2/31 • Number of events 3 • 60 months
|
|
Eye disorders
Night blindness
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Non-cardiac chest pain
|
8.2%
11/134 • Number of events 17 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
14.1%
9/64 • Number of events 24 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Oral dysesthesia
|
6.0%
8/134 • Number of events 41 • 60 months
|
0.00%
0/69 • 60 months
|
6.2%
4/64 • Number of events 31 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Oral hemorrhage
|
0.75%
1/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Oral pain
|
3.0%
4/134 • Number of events 10 • 60 months
|
0.00%
0/69 • 60 months
|
7.8%
5/64 • Number of events 36 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 6 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Otitis media
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Pain
|
11.2%
15/134 • Number of events 47 • 60 months
|
10.1%
7/69 • Number of events 33 • 60 months
|
6.2%
4/64 • Number of events 6 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.2%
7/134 • Number of events 66 • 60 months
|
2.9%
2/69 • Number of events 4 • 60 months
|
4.7%
3/64 • Number of events 34 • 60 months
|
3.2%
1/31 • Number of events 3 • 60 months
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrm
|
35.1%
47/134 • Number of events 334 • 60 months
|
7.2%
5/69 • Number of events 8 • 60 months
|
37.5%
24/64 • Number of events 247 • 60 months
|
16.1%
5/31 • Number of events 10 • 60 months
|
|
Cardiac disorders
Palpitations
|
0.00%
0/134 • 60 months
|
2.9%
2/69 • Number of events 23 • 60 months
|
3.1%
2/64 • Number of events 11 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Papulopustular rash
|
0.75%
1/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 7 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Paresthesia
|
2.2%
3/134 • Number of events 11 • 60 months
|
2.9%
2/69 • Number of events 24 • 60 months
|
7.8%
5/64 • Number of events 32 • 60 months
|
3.2%
1/31 • Number of events 3 • 60 months
|
|
Infections and infestations
Paronychia
|
1.5%
2/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Reproductive system and breast disorders
Pelvic pain
|
1.5%
2/134 • Number of events 13 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
1.6%
1/64 • Number of events 23 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Infections and infestations
Penile infection
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Periodontal disease
|
0.75%
1/134 • Number of events 11 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Eye disorders
Periorbital edema
|
2.2%
3/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Peripheral motor neuropathy
|
3.7%
5/134 • Number of events 15 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
6.5%
2/31 • Number of events 5 • 60 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
7.5%
10/134 • Number of events 90 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
6.2%
4/64 • Number of events 12 • 60 months
|
9.7%
3/31 • Number of events 5 • 60 months
|
|
Vascular disorders
Phlebitis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Platelet count decreased
|
55.2%
74/134 • Number of events 434 • 60 months
|
11.6%
8/69 • Number of events 30 • 60 months
|
37.5%
24/64 • Number of events 149 • 60 months
|
19.4%
6/31 • Number of events 21 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.75%
1/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.75%
1/134 • Number of events 19 • 60 months
|
2.9%
2/69 • Number of events 8 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 9 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
2.2%
3/134 • Number of events 13 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
3.1%
2/64 • Number of events 4 • 60 months
|
0.00%
0/31 • 60 months
|
|
Injury, poisoning and procedural complications
Postoperative hemorrhage
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Reproductive system and breast disorders
Premature menopause
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Presyncope
|
1.5%
2/134 • Number of events 20 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Gastrointestinal disorders
Proctitis
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.7%
9/134 • Number of events 16 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Proteinuria
|
8.2%
11/134 • Number of events 49 • 60 months
|
4.3%
3/69 • Number of events 6 • 60 months
|
6.2%
4/64 • Number of events 18 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.0%
8/134 • Number of events 22 • 60 months
|
2.9%
2/69 • Number of events 5 • 60 months
|
1.6%
1/64 • Number of events 25 • 60 months
|
6.5%
2/31 • Number of events 3 • 60 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
1.5%
2/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
27.6%
37/134 • Number of events 141 • 60 months
|
4.3%
3/69 • Number of events 5 • 60 months
|
21.9%
14/64 • Number of events 77 • 60 months
|
12.9%
4/31 • Number of events 6 • 60 months
|
|
Infections and infestations
Rash pustular
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Rectal fistula
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
2.2%
3/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Rectal mucositis
|
0.75%
1/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Rectal pain
|
3.0%
4/134 • Number of events 16 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 10 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Rectal ulcer
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Oth spec
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
3.1%
2/64 • Number of events 16 • 60 months
|
6.5%
2/31 • Number of events 10 • 60 months
|
|
Renal and urinary disorders
Renal calculi
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 5 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Reproductive system and breast disorders
Reproductive system and breast -Oth spec
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic, mediastinal - Oth spec
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
4.7%
3/64 • Number of events 9 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
1.5%
2/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Scalp pain
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Nervous system disorders
Seizure
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 3 • 60 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Serum amylase increased
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 6 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Metabolism and nutrition disorders
Anorexia
|
35.1%
47/134 • Number of events 262 • 60 months
|
13.0%
9/69 • Number of events 28 • 60 months
|
21.9%
14/64 • Number of events 80 • 60 months
|
16.1%
5/31 • Number of events 14 • 60 months
|
|
Nervous system disorders
Anosmia
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Psychiatric disorders
Anxiety
|
9.0%
12/134 • Number of events 103 • 60 months
|
4.3%
3/69 • Number of events 24 • 60 months
|
9.4%
6/64 • Number of events 43 • 60 months
|
12.9%
4/31 • Number of events 13 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.0%
4/134 • Number of events 20 • 60 months
|
2.9%
2/69 • Number of events 2 • 60 months
|
10.9%
7/64 • Number of events 31 • 60 months
|
3.2%
1/31 • Number of events 1 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
4.5%
6/134 • Number of events 45 • 60 months
|
1.4%
1/69 • Number of events 21 • 60 months
|
3.1%
2/64 • Number of events 6 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Gastrointestinal disorders
Ascites
|
2.2%
3/134 • Number of events 17 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Aspartate aminotransferase increased
|
71.6%
96/134 • Number of events 595 • 60 months
|
24.6%
17/69 • Number of events 38 • 60 months
|
78.1%
50/64 • Number of events 370 • 60 months
|
48.4%
15/31 • Number of events 30 • 60 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.7%
17/134 • Number of events 104 • 60 months
|
14.5%
10/69 • Number of events 32 • 60 months
|
12.5%
8/64 • Number of events 38 • 60 months
|
12.9%
4/31 • Number of events 8 • 60 months
|
|
Gastrointestinal disorders
Belching
|
1.5%
2/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 7 • 60 months
|
0.00%
0/31 • 60 months
|
|
Hepatobiliary disorders
Biliary fistula
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Bladder infection
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Bloating
|
7.5%
10/134 • Number of events 66 • 60 months
|
4.3%
3/69 • Number of events 12 • 60 months
|
6.2%
4/64 • Number of events 45 • 60 months
|
0.00%
0/31 • 60 months
|
|
Blood and lymphatic system disorders
Blood and lymph sys disorders - Oth Spec
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 2 • 60 months
|
1.6%
1/64 • Number of events 5 • 60 months
|
0.00%
0/31 • 60 months
|
|
Metabolism and nutrition disorders
Blood bicarbonate decreased
|
0.00%
0/134 • 60 months
|
1.4%
1/69 • Number of events 6 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Blood bilirubin increased
|
14.9%
20/134 • Number of events 72 • 60 months
|
7.2%
5/69 • Number of events 9 • 60 months
|
12.5%
8/64 • Number of events 13 • 60 months
|
3.2%
1/31 • Number of events 3 • 60 months
|
|
Investigations
Blood lactate dehydrogenase increased
|
6.7%
9/134 • Number of events 102 • 60 months
|
0.00%
0/69 • 60 months
|
6.2%
4/64 • Number of events 43 • 60 months
|
0.00%
0/31 • 60 months
|
|
Eye disorders
Blurred vision
|
4.5%
6/134 • Number of events 31 • 60 months
|
4.3%
3/69 • Number of events 5 • 60 months
|
6.2%
4/64 • Number of events 35 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
3.0%
4/134 • Number of events 49 • 60 months
|
4.3%
3/69 • Number of events 12 • 60 months
|
1.6%
1/64 • Number of events 37 • 60 months
|
0.00%
0/31 • 60 months
|
|
Reproductive system and breast disorders
Breast pain
|
0.00%
0/134 • 60 months
|
2.9%
2/69 • Number of events 3 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Bronchial infection
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
3.2%
1/31 • Number of events 2 • 60 months
|
|
Injury, poisoning and procedural complications
Bruising
|
3.0%
4/134 • Number of events 29 • 60 months
|
0.00%
0/69 • 60 months
|
6.2%
4/64 • Number of events 52 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Bullous dermatitis
|
0.75%
1/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
3.0%
4/134 • Number of events 22 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Cardiac disorders - Other, specify
|
3.7%
5/134 • Number of events 53 • 60 months
|
2.9%
2/69 • Number of events 17 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Investigations
Cardiac troponin I increased
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 9 • 60 months
|
0.00%
0/31 • 60 months
|
|
Eye disorders
Cataract
|
0.75%
1/134 • Number of events 13 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Cheilitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 1 • 60 months
|
0.00%
0/31 • 60 months
|
|
Cardiac disorders
Chest pain - cardiac
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
1.5%
2/134 • Number of events 6 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
General disorders
Chills
|
6.0%
8/134 • Number of events 15 • 60 months
|
1.4%
1/69 • Number of events 1 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
6.5%
2/31 • Number of events 2 • 60 months
|
|
Investigations
Cholesterol high
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 8 • 60 months
|
4.7%
3/64 • Number of events 20 • 60 months
|
0.00%
0/31 • 60 months
|
|
Renal and urinary disorders
Chronic kidney disease
|
1.5%
2/134 • Number of events 17 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 26 • 60 months
|
3.2%
1/31 • Number of events 3 • 60 months
|
|
Gastrointestinal disorders
Colitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Psychiatric disorders
Confusion
|
2.2%
3/134 • Number of events 7 • 60 months
|
1.4%
1/69 • Number of events 3 • 60 months
|
3.1%
2/64 • Number of events 2 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Conjunctivitis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Infections and infestations
Conjunctivitis infective
|
0.75%
1/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Constipation
|
16.4%
22/134 • Number of events 122 • 60 months
|
13.0%
9/69 • Number of events 30 • 60 months
|
12.5%
8/64 • Number of events 63 • 60 months
|
25.8%
8/31 • Number of events 27 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.2%
15/134 • Number of events 77 • 60 months
|
10.1%
7/69 • Number of events 9 • 60 months
|
15.6%
10/64 • Number of events 20 • 60 months
|
3.2%
1/31 • Number of events 4 • 60 months
|
|
Investigations
Creatinine increased
|
23.1%
31/134 • Number of events 124 • 60 months
|
13.0%
9/69 • Number of events 21 • 60 months
|
7.8%
5/64 • Number of events 48 • 60 months
|
19.4%
6/31 • Number of events 9 • 60 months
|
|
Metabolism and nutrition disorders
Dehydration
|
9.0%
12/134 • Number of events 18 • 60 months
|
2.9%
2/69 • Number of events 4 • 60 months
|
7.8%
5/64 • Number of events 8 • 60 months
|
6.5%
2/31 • Number of events 4 • 60 months
|
|
Psychiatric disorders
Delusions
|
0.75%
1/134 • Number of events 2 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Dental caries
|
1.5%
2/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Alanine aminotransferase increased
|
66.4%
89/134 • Number of events 455 • 60 months
|
21.7%
15/69 • Number of events 31 • 60 months
|
76.6%
49/64 • Number of events 355 • 60 months
|
38.7%
12/31 • Number of events 29 • 60 months
|
|
Investigations
Alkaline phosphatase increased
|
28.4%
38/134 • Number of events 186 • 60 months
|
24.6%
17/69 • Number of events 50 • 60 months
|
21.9%
14/64 • Number of events 98 • 60 months
|
29.0%
9/31 • Number of events 32 • 60 months
|
|
Immune system disorders
Allergic reaction
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Psychiatric disorders
Depression
|
9.0%
12/134 • Number of events 90 • 60 months
|
7.2%
5/69 • Number of events 39 • 60 months
|
0.00%
0/64 • 60 months
|
9.7%
3/31 • Number of events 9 • 60 months
|
|
Gastrointestinal disorders
Diarrhea
|
61.2%
82/134 • Number of events 773 • 60 months
|
44.9%
31/69 • Number of events 145 • 60 months
|
62.5%
40/64 • Number of events 369 • 60 months
|
32.3%
10/31 • Number of events 28 • 60 months
|
|
Nervous system disorders
Dizziness
|
16.4%
22/134 • Number of events 60 • 60 months
|
5.8%
4/69 • Number of events 9 • 60 months
|
25.0%
16/64 • Number of events 32 • 60 months
|
0.00%
0/31 • 60 months
|
|
Eye disorders
Dry eye
|
0.75%
1/134 • Number of events 1 • 60 months
|
1.4%
1/69 • Number of events 15 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
8.2%
11/134 • Number of events 62 • 60 months
|
0.00%
0/69 • 60 months
|
4.7%
3/64 • Number of events 24 • 60 months
|
0.00%
0/31 • 60 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.2%
11/134 • Number of events 93 • 60 months
|
0.00%
0/69 • 60 months
|
10.9%
7/64 • Number of events 72 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Anal fissure
|
0.75%
1/134 • Number of events 21 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Anal fistula
|
0.75%
1/134 • Number of events 4 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Anal hemorrhage
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 4 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Anal pain
|
0.75%
1/134 • Number of events 5 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Blood and lymphatic system disorders
Anemia
|
32.8%
44/134 • Number of events 256 • 60 months
|
24.6%
17/69 • Number of events 63 • 60 months
|
28.1%
18/64 • Number of events 113 • 60 months
|
29.0%
9/31 • Number of events 38 • 60 months
|
|
Infections and infestations
Anorectal infection
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Abdominal distension
|
0.75%
1/134 • Number of events 3 • 60 months
|
0.00%
0/69 • 60 months
|
1.6%
1/64 • Number of events 9 • 60 months
|
0.00%
0/31 • 60 months
|
|
Gastrointestinal disorders
Abdominal pain
|
25.4%
34/134 • Number of events 159 • 60 months
|
31.9%
22/69 • Number of events 48 • 60 months
|
20.3%
13/64 • Number of events 75 • 60 months
|
9.7%
3/31 • Number of events 14 • 60 months
|
|
Metabolism and nutrition disorders
Acidosis
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
|
Investigations
Activated partial throm time prolonged
|
0.00%
0/134 • 60 months
|
0.00%
0/69 • 60 months
|
3.1%
2/64 • Number of events 20 • 60 months
|
0.00%
0/31 • 60 months
|
|
Psychiatric disorders
Agitation
|
0.75%
1/134 • Number of events 1 • 60 months
|
0.00%
0/69 • 60 months
|
0.00%
0/64 • 60 months
|
0.00%
0/31 • 60 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60