Trial Outcomes & Findings for A Trial of Tisotumab Vedotin in Cervical Cancer (NCT NCT03438396)
NCT ID: NCT03438396
Last Updated: 2023-07-25
Results Overview
The confirmed OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based upon RECIST v1.1, assessed by the IRC. The CR is disappearance of all target and non-target lesions and no new lesions. A confirmed CR is 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (Not Evaluable \[NE\]) scan evaluations between response scan and confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
102 participants
Primary outcome timeframe
From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 20 months)
Results posted on
2023-07-25
Participant Flow
This study was conducted in Europe and the US.
A 102 participants with Recurrent or Metastatic Cervical Cancer were enrolled in the study and out of which 101 participants received study treatment. These participants were assessed until the participant experienced IRC-verified disease progression, started new anti-cancer therapy, discontinued the trial, or died.
Participant milestones
| Measure |
Tisotumab Vedotin
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Overall Study
STARTED
|
102
|
|
Overall Study
Treated
|
101
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
102
|
Reasons for withdrawal
| Measure |
Tisotumab Vedotin
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Overall Study
Reason Not Specified
|
9
|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Death
|
85
|
|
Overall Study
Not treated
|
1
|
Baseline Characteristics
A Trial of Tisotumab Vedotin in Cervical Cancer
Baseline characteristics by cohort
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Age, Continuous
|
50.66 Years
STANDARD_DEVIATION 10.71 • n=99 Participants
|
|
Sex: Female, Male
Female
|
101 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
95 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
95 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 20 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
The confirmed OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based upon RECIST v1.1, assessed by the IRC. The CR is disappearance of all target and non-target lesions and no new lesions. A confirmed CR is 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (Not Evaluable \[NE\]) scan evaluations between response scan and confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Percentage of Participants With Confirmed Objective Response (OR) as Assessed by the Independent Review Committee (IRC)
|
23.8 Percentage of Participants
Interval 15.9 to 33.3
|
SECONDARY outcome
Timeframe: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The DOR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the IRC.
The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented progression disease (PD) verified by IRC or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Tisotumab Vedotin
n=24 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Duration of Response (DOR) as Assessed by the IRC
|
8.3 Months
Interval 4.2 to 13.5
|
SECONDARY outcome
Timeframe: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
The confirmed OR is defined as best overall response of confirmed CR or confirmed PR based upon RECIST v1.1, assessed by the investigator. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is defined as PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (NE) scan evaluations between the response scan and the confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Percentage of Participants With Confirmed OR as Assessed by the Investigator
|
20.8 Percentage of Participants
Interval 13.4 to 30.0
|
SECONDARY outcome
Timeframe: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The DOR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the investigator.
The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented PD verified by investigator or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Tisotumab Vedotin
n=21 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
DOR as Assessed by the Investigator
|
8.2 Months
Interval 3.7 to 18.4
|
SECONDARY outcome
Timeframe: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The TTR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the IRC.
The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the IRC. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between.
Outcome measures
| Measure |
Tisotumab Vedotin
n=24 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Time to Response (TTR) as Assessed by the IRC
|
1.4 Months
Interval 1.1 to 5.1
|
SECONDARY outcome
Timeframe: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The TTR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the investigator.
The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the investigator. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between.
Outcome measures
| Measure |
Tisotumab Vedotin
n=21 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
TTR as Assessed by the Investigator
|
1.4 Months
Interval 1.1 to 4.5
|
SECONDARY outcome
Timeframe: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the IRC or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Progression Free Survival (PFS) as Assessed by the IRC
|
4.2 Months
Interval 3.0 to 4.4
|
SECONDARY outcome
Timeframe: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the investigator or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
PFS as Assessed by the Investigator
|
4.1 Months
Interval 3.3 to 4.6
|
SECONDARY outcome
Timeframe: From Day 1 until death or withdrawal from the study, whichever occurred first (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Overall Survival (OS)
|
12.3 Months
Interval 9.6 to 14.1
|
SECONDARY outcome
Timeframe: From Day 1 through 30 days after the last dose of study drug (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is "medically important"\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of tisotumab vedotin and 30 days after the last dose received.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Any TEAE
|
101 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Any TESAE
|
44 Participants
|
SECONDARY outcome
Timeframe: From Day 1 through 30 days after the last dose of study drug (approximately 49 months)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
Laboratory abnormalities that induced clinical signs or symptoms, required concomitant therapy or required changes during treatment emergent period were reported as TEAEs. Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Anaemia
|
34 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Thrombocytopenia
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Neutropenia
|
4 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Iron deficiency anaemia
|
3 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Leukocytosis
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Leukopenia
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Thrombocytosis
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypokalaemia
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypomagnesaemia
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypocalcaemia
|
4 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hyperglycaemia
|
3 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypercreatininaemia
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hyperuricaemia
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypercalcaemia
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypernatraemia
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypoalbuminaemia
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hyponatraemia
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Activated partial thromboplastin time prolonged
|
3 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Neutrophil count decreased
|
3 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Blood creatinine increased
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
C-reactive protein increased
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
International normalised ratio increased
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Lymphocyte count decreased
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Alanine aminotransferase increased
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Aspartate aminotransferase increased
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Blood alkaline phosphatase increased
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Blood bicarbonate decreased
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Blood creatine phosphokinase increased
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Blood potassium decreased
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Creatinine renal clearance decreased
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Platelet count decreased
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Prothrombin time prolonged
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
White blood cell count decreased
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hyperthyroidism
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypothyroidism
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypertransaminasaemia
|
3 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hyperbilirubinaemia
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Haematuria
|
10 Participants
|
SECONDARY outcome
Timeframe: Predose and end of infusion of Cycle 1 Day 1 (C1D1) and Cycle 6 Day 1 (C6D1)Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
Plasma concentrations of HuMax-TF, HuMax-TF-ADC, and Free MMAE measures on Cycle 1 Day 1 (predose and end of infusion) and Cycle 6 Day 1 (predose and end of infusion) are reported.
Outcome measures
| Measure |
Tisotumab Vedotin
n=101 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF (C1D1-predose)
|
163.48 ng/mL
Geometric Coefficient of Variation 60.70
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF (C1D1-end of infusion)
|
41691.0 ng/mL
Geometric Coefficient of Variation 68.02
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF (C6D1-predose)
|
150.0 ng/mL
Geometric Coefficient of Variation 0.0
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF (C6D1-end of infusion)
|
36941 ng/mL
Geometric Coefficient of Variation 25.88
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF-ADC (C1D1-predose)
|
30.0 ng/mL
Geometric Coefficient of Variation 0.0
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF-ADC (C1D1-end of infusion)
|
38105 ng/mL
Geometric Coefficient of Variation 92.62
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF-ADC (C6D1-predose)
|
30.0 ng/mL
Geometric Coefficient of Variation 0.0
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
HuMax-TF-ADC (C6D1-end of infusion)
|
36270.0 ng/mL
Geometric Coefficient of Variation 28.29
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
MMAE (C1D1-predose)
|
12.50 ng/mL
Geometric Coefficient of Variation 0.0
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
MMAE (C1D1-end of infusion)
|
171.27 ng/mL
Geometric Coefficient of Variation 102.05
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
MMAE (C6D1-predose)
|
46.71 ng/mL
Geometric Coefficient of Variation 146.11
|
|
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
MMAE (C6D1-end of infusion)
|
177.46 ng/mL
Geometric Coefficient of Variation 82.62
|
SECONDARY outcome
Timeframe: Predose of each treatment cycle (Cycle 1 to 21) and end of treatment visit (approximately 49 months)Population: Participants in FAS (received at least 1 dose of tisotumab vedotin) and who had ADA results at baseline and post-baseline are analyzed for this outcome measure.
Number of participants with positive ADA titer to tisotumab vedotin at baseline and post-baseline are reported. Baseline is defined as the latest available measurement made before the first dose of tisotumab vedotin. For post-baseline results, a participant was considered ADA positive if either ADA is negative at baseline and at least one post-baseline result is positive or positive at baseline and at least one positive post-baseline result with a titer higher than baseline.
Outcome measures
| Measure |
Tisotumab Vedotin
n=93 Participants
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin
ADA positive at Baseline
|
2 Participants
|
|
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin
ADA positive at post-baseline
|
5 Participants
|
Adverse Events
Tisotumab Vedotin
Serious events: 44 serious events
Other events: 99 other events
Deaths: 86 deaths
Serious adverse events
| Measure |
Tisotumab Vedotin
n=101 participants at risk
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Infections and infestations
Pneumonia
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Septic shock
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Urinary tract infection
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Cellulitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Lower respiratory tract infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Neutropenic sepsis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Respiratory tract infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Urosepsis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Constipation
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Ileus
|
2.0%
2/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Subileus
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Vomiting
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Pyrexia
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Death
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Asthenia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Infusion site extravasation
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Non-cardiac chest pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Pain
|
0.99%
1/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Urinary tract obstruction
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Acute kidney injury
|
0.99%
1/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Cystitis haemorrhagic
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Haematuria
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Renal failure
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Fistula discharge
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
General physical condition abnormal
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Lymphoedema
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Ulcerative Keratitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
Other adverse events
| Measure |
Tisotumab Vedotin
n=101 participants at risk
Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first.
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
40.6%
41/101 • Number of events 51 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
24.8%
25/101 • Number of events 29 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Constipation
|
19.8%
20/101 • Number of events 20 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Vomiting
|
16.8%
17/101 • Number of events 25 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
12.9%
13/101 • Number of events 18 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Dry mouth
|
7.9%
8/101 • Number of events 8 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.9%
6/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Fatigue
|
34.7%
35/101 • Number of events 47 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Asthenia
|
17.8%
18/101 • Number of events 18 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Pyrexia
|
14.9%
15/101 • Number of events 38 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Influenza like illness
|
6.9%
7/101 • Number of events 7 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Oedema peripheral
|
7.9%
8/101 • Number of events 9 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
38.6%
39/101 • Number of events 39 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
13.9%
14/101 • Number of events 18 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.9%
14/101 • Number of events 16 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.9%
6/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Conjunctivitis
|
30.7%
31/101 • Number of events 49 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Urinary tract infection
|
9.9%
10/101 • Number of events 12 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Nasopharyngitis
|
6.9%
7/101 • Number of events 7 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.8%
17/101 • Number of events 25 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.8%
17/101 • Number of events 26 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.9%
13/101 • Number of events 13 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.9%
8/101 • Number of events 8 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.0%
5/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.9%
7/101 • Number of events 7 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Dry eye
|
24.8%
25/101 • Number of events 30 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Keratitis
|
10.9%
11/101 • Number of events 15 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Blepharitis
|
6.9%
7/101 • Number of events 10 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Punctate keratitis
|
5.9%
6/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
38.6%
39/101 • Number of events 49 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.9%
9/101 • Number of events 9 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.9%
6/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Neuropathy peripheral
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
18.8%
19/101 • Number of events 24 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Headache
|
7.9%
8/101 • Number of events 12 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
32.7%
33/101 • Number of events 39 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
17.8%
18/101 • Number of events 19 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.9%
6/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.9%
6/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Weight decreased
|
13.9%
14/101 • Number of events 14 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Haematuria
|
8.9%
9/101 • Number of events 11 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
9.9%
10/101 • Number of events 13 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Psychiatric disorders
Insomnia
|
9.9%
10/101 • Number of events 10 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Abdominal distension
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Anal haemorrhage
|
0.99%
1/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Anal incontinence
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Colitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Duodenogastric reflux
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Dyschezia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Enteritis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Flatulence
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Gastritis
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Gingival bleeding
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Haematochezia
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Haemorrhoids
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Large intestinal haemorrhage
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Oesophagitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Retching
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Small intestinal stenosis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Stomatitis
|
3.0%
3/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Gastrointestinal disorders
Subileus
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Face oedema
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Chest discomfort
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Chest pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Chills
|
3.0%
3/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Facial pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Gait disturbance
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Infusion site coldness
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Localised oedema
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Malaise
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Mucosal disorder
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Mucosal inflammation
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Nodule
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Non-cardiac chest pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Oedema
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Pain
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Peripheral swelling
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
General disorders
Thirst
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.0%
5/101 • Number of events 5 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
3.0%
3/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
0.99%
1/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Abscess limb
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Bronchitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Catheter site infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Clostridium difficile colitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Corona virus infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Cystitis
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Device related infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Diverticulitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Folliculitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Gastroenteritis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Genital herpes
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Gingivitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Herpes ophthalmic
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Herpes zoster
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Herpes zoster oticus
|
0.99%
1/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Parotitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Pharyngitis streptococcal
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Respiratory tract infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Rhinitis
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Stenotrophomonas infection
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Tooth abscess
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
5.9%
6/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Infections and infestations
Vaginal infection
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
3.0%
3/101 • Number of events 5 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Hypercreatinaemia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Amblyopia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Asthenopia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Blepharospasm
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Cataract
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Chalazion
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Conjunctival erosion
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Conjunctival haemorrhage
|
2.0%
2/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal obstruction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.0%
5/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Vision blurred
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Ulcerative keratitis
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Trichiasis
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Retinal exudates
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Photophobia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Ocular hypertension
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Ocular hyperaemia
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Noninfective conjunctivitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Meibomianitis
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Meibomian gland dysfunction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Lacrimation increased
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Keratopathy
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Foreign body sensation in eyes
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Eye pruritus
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Eye pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Eye movement disorder
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Eye irritation
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Eye inflammation
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Eye discharge
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Entropion
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Corneal scar
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Corneal erosion
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Corneal bleeding
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Eye disorders
Conjunctival hyperaemia
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.0%
4/101 • Number of events 5 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Sensory loss
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Sciatica
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus discomfort
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus haemorrhage
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Polyneuropathy
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Peripheral motor neuropathy
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Paraesthesia
|
4.0%
4/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Neuralgia
|
2.0%
2/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Hypoaesthesia
|
3.0%
3/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Hyperaesthesia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Dysgeusia
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Dizziness
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Nervous system disorders
Burning sensation
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Weight increased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Prothrombin time prolonged
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Platelet count decreased
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Neutrophil count decreased
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Lymphocyte count decreased
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
International normalised ratio increased
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
4.0%
4/101 • Number of events 5 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
2.0%
2/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
4.0%
4/101 • Number of events 5 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Electrocardiogram QT prolonged
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Ejection fraction decreased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
C-reactive protein increased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Blood potassium decreased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Blood creatinine increased
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Blood creatine phosphokinase increased
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Blood bicarbonate decreased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Blood alkaline phosphatase increased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Aspartate aminotransferase increased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Alanine aminotransferase increased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Activated partial thromboplastin time prolonged
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
White blood cell count decreased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Investigations
Creatinine renal clearance decreased
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Psychiatric disorders
Anxiety
|
5.0%
5/101 • Number of events 5 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Psychiatric disorders
Depression
|
4.0%
4/101 • Number of events 4 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Urinary tract disorder
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Urinary incontinence
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Urinary bladder haemorrhage
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Ureteric obstruction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Renal failure
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Hydronephrosis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Dysuria
|
5.0%
5/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Chromaturia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Renal and urinary disorders
Bladder outlet obstruction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Psychiatric disorders
Depressed mood
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Vulvovaginal pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Vaginal ulceration
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Vaginal fistula
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Vaginal discharge
|
4.0%
4/101 • Number of events 5 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Rectocele
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Pelvic pain
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Genital swelling
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Genital prolapse
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Reproductive system and breast disorders
Cystocele
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acoustic neuroma
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Immune system disorders
Allergy to metals
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Endocrine disorders
Hypothyroidism
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Endocrine disorders
Hyperthyroidism
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Ear and labyrinth disorders
Vertigo
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Ear and labyrinth disorders
Tinnitus
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Cardiac disorders
Sinus tachycardia
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Cardiac disorders
Myocardial infarction
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Hot flush
|
5.0%
5/101 • Number of events 6 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Deep vein thrombosis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Aortic thrombosis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Urinary tract stoma complication
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.99%
1/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Radiation proctitis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Radiation associated haemorrhage
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Contusion
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Conjunctival scar
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Injury, poisoning and procedural complications
Conjunctival abrasion
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Hypertension
|
2.0%
2/101 • Number of events 2 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Venous thrombosis limb
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Thrombosis
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Lymphoedema
|
3.0%
3/101 • Number of events 3 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
|
Vascular disorders
Hypotension
|
0.99%
1/101 • Number of events 1 • From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is at least 12 months but less than 18 months from the end of study (database lock). The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER