Trial Outcomes & Findings for Study of HBI-8000 With Nivolumab in Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer (NCT NCT02718066)
NCT ID: NCT02718066
Last Updated: 2026-07-30
Results Overview
The dose escalation schema of HBI 8000 followed the conventional 3+3 design. The starting dose was HBI 8000 20 mg twice a week. Dose escalation to 30 mg or 40 mg was determined by observation of DLT. At each dose level, a minimum of 3 subjects evaluable for DLT were enrolled. If 0 of the initial 3, or no more than 1 in a total 6 subjects experienced DLT, escalation to the next higher dose was allowed.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
96 participants
Primary outcome timeframe
First 28 days
Results posted on
2026-07-30
Participant Flow
The first subject enrolled 18 August 2016 and the last subject enrolled 19 January 2021. All sites were located in the US.
Subjects with advanced cancers, including melanoma, renal cell carcinoma and non-small cell lung cancer, for which nivolumab therapy is appropriate, were recruited.
Participant milestones
| Measure |
Phase 1b: HBI-8000 20 mg in Combination With Nivolumab
Phase 1b Cohort 1: HBI-8000 20 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 30 mg in Combination With Nivolumab
Phase 1b Cohort 2: HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 40 mg in Combination With Nivolumab
Phase 1b Cohort 3: HBI-8000 40 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 2: HBI-8000 30 mg in Combination With Nivolumab
HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing.
Nivolumab 240 mg was administered via intravenous infusions every 2 weeks or 480 mg was administered via intravenous infusions every 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
7
|
7
|
79
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
2
|
|
Overall Study
NOT COMPLETED
|
3
|
7
|
7
|
77
|
Reasons for withdrawal
| Measure |
Phase 1b: HBI-8000 20 mg in Combination With Nivolumab
Phase 1b Cohort 1: HBI-8000 20 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 30 mg in Combination With Nivolumab
Phase 1b Cohort 2: HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 40 mg in Combination With Nivolumab
Phase 1b Cohort 3: HBI-8000 40 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 2: HBI-8000 30 mg in Combination With Nivolumab
HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing.
Nivolumab 240 mg was administered via intravenous infusions every 2 weeks or 480 mg was administered via intravenous infusions every 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
5
|
|
Overall Study
Death
|
2
|
4
|
7
|
28
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
4
|
|
Overall Study
Other - Majority: Completion of Survival Follow-up
|
1
|
2
|
0
|
40
|
Baseline Characteristics
Study of HBI-8000 With Nivolumab in Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Phase 1b: HBI-8000 20 mg in Combination With Nivolumab
n=3 Participants
Phase 1b Cohort 1: HBI-8000 20 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 30 mg in Combination With Nivolumab
n=7 Participants
Phase 1b Cohort 2: HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 40 mg in Combination With Nivolumab
n=7 Participants
Phase 1b Cohort 3: HBI-8000 40 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 2: HBI-8000 30 mg in Combination With Nivolumab
n=79 Participants
HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing.
Nivolumab 240 mg was administered via intravenous infusions every 2 weeks or 480 mg was administered via intravenous infusions every 4 weeks.
|
Total
n=96 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=9 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=20 Participants
|
3 Participants
n=20 Participants
|
1 Participants
n=40 Participants
|
40 Participants
n=5 Participants
|
45 Participants
n=9 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=20 Participants
|
4 Participants
n=20 Participants
|
6 Participants
n=40 Participants
|
39 Participants
n=5 Participants
|
51 Participants
n=9 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
3 Participants
n=40 Participants
|
35 Participants
n=5 Participants
|
40 Participants
n=9 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=20 Participants
|
6 Participants
n=20 Participants
|
4 Participants
n=40 Participants
|
44 Participants
n=5 Participants
|
56 Participants
n=9 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=9 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=20 Participants
|
6 Participants
n=20 Participants
|
7 Participants
n=40 Participants
|
73 Participants
n=5 Participants
|
89 Participants
n=9 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
White
|
3 Participants
n=20 Participants
|
7 Participants
n=20 Participants
|
7 Participants
n=40 Participants
|
73 Participants
n=5 Participants
|
90 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=9 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=20 Participants
|
7 participants
n=20 Participants
|
7 participants
n=40 Participants
|
79 participants
n=5 Participants
|
96 participants
n=9 Participants
|
PRIMARY outcome
Timeframe: First 28 daysPopulation: Dose Limiting Toxicity Set included patients who received at least 75% of the planned dose in the first 28 days (Cycle 1).
The dose escalation schema of HBI 8000 followed the conventional 3+3 design. The starting dose was HBI 8000 20 mg twice a week. Dose escalation to 30 mg or 40 mg was determined by observation of DLT. At each dose level, a minimum of 3 subjects evaluable for DLT were enrolled. If 0 of the initial 3, or no more than 1 in a total 6 subjects experienced DLT, escalation to the next higher dose was allowed.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=3 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Number of Patients Who Experienced at Least One DLT During the DLT Assessment Period for MTD Determination
|
0 patients
|
0 patients
|
2 patients
|
—
|
SECONDARY outcome
Timeframe: From screening for baseline assessment to the date of CR or PR assessed, up to approximately 4 years and 7 monthsPopulation: Patients who were treated at RP2D and were evaluable for efficacy, met all eligibility criteria, received at least one dose of HBI 8000, and either had at least one post baseline assessment of efficacy by imaging studies or discontinued study early due to clinical progressive disease in the absence of imaging study.
Percentage of patients with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=53 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=22 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=81 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Objective Response Rate (ORR) in All Patients Treated at RP2D
|
56.6 Percentage of patients
Interval 42.3 to 70.2
|
22.7 Percentage of patients
Interval 7.8 to 45.4
|
16.7 Percentage of patients
Interval 0.4 to 64.1
|
44.4 Percentage of patients
Interval 33.4 to 55.9
|
SECONDARY outcome
Timeframe: From screening for baseline assessment to the date of best response (CR, PR, or SD) on study, up to approximately 4 years and 7 monthsPopulation: Patients who were treated at RP2D and were evaluable for efficacy, met all eligibility criteria, received at least one dose of HBI 8000, and either had at least one post baseline assessment of efficacy by imaging studies or discontinued study early due to clinical progressive disease in the absence of imaging study.
Percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=53 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=22 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=81 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Disease Control Rate (DCR) in All Patients Treated at RP2D
|
84.9 Percentage of patients
Interval 72.4 to 93.3
|
68.2 Percentage of patients
Interval 45.1 to 86.1
|
66.7 Percentage of patients
Interval 22.3 to 95.7
|
79.0 Percentage of patients
Interval 68.5 to 87.3
|
SECONDARY outcome
Timeframe: From the date of CR or PR until the date of PD, or until the date of death, up to approximately 4 years and 7 monthsPopulation: Patients who were treated at RP2D and were evaluable for efficacy, met all eligibility criteria, received at least one dose of HBI 8000, and either had at least one post baseline assessment of efficacy by imaging studies or discontinued study early due to clinical progressive disease in the absence of imaging study.
Time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=53 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=22 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=81 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Duration of Response (DoR) in All Patients Treated at RP2D
|
NA Weeks
The median DoR and its 95% confidence interval could not be estimated due to an insufficient number of events at the time of analysis.
|
32.0 Weeks
Interval 15.9 to
The median DoR was estimable; however, the upper limit of the 95% confidence interval could not be estimated due to an insufficient number of events at the time of analysis.
|
89.4 Weeks
The median DoR was estimable; however, the 95% confidence interval could not be estimated due to an insufficient number of events at the time of analysis.
|
NA Weeks
Interval 81.1 to
The median DoR and the upper limit of the corresponding 95% confidence interval could not be estimated due to an insufficient number of events at the time of analysis.
|
SECONDARY outcome
Timeframe: From the date of first dose of HBI-8000 until tumor progression by site reported RECIST 1.1, or clinical progression, or death, whichever occurs first, up to approximately 4 years and 7 monthsPopulation: Patients who were treated at RP2D and were evaluable for efficacy, met all eligibility criteria, received at least one dose of HBI 8000, and either had at least one post baseline assessment of efficacy by imaging studies or discontinued study early due to clinical progressive disease in the absence of imaging study.
Time from the date of first dose of HBI-8000 until tumor progression by site reported RECIST 1.1, or clinical progression, or death, whichever occurs first. If tumor progression data include more than 1 date of progression, the earliest date will be used.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=53 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=22 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=81 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Progression-Free Survival (PFS) in All Patients Treated at RP2D
|
79.6 Weeks
Interval 24.9 to
The median PFS was estimable; however, the upper limit of the 95% confidence interval could not be estimated due to an insufficient number of events at the time of analysis.
|
10.1 Weeks
Interval 7.6 to 55.7
|
14.6 Weeks
Interval 7.6 to
The median PFS was estimable; however, the upper limit of the 95% confidence interval could not be estimated due to an insufficient number of events at the time of analysis.
|
34.7 Weeks
Interval 22.1 to 70.4
|
SECONDARY outcome
Timeframe: From predose (0.5 hour prior to breakfast) to 7 hours postdose on Cycle 1 Day 1, at 24 hours on Cycle 1 Day 2 (no dose administered)Population: All patients in Phase 1b and patients at selected sites in Phase 2, who received at least one dose of HBI-8000 and had at least one postdose blood sample providing evaluable PK data for HBI-8000.
Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=3 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=8 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Pharmacokinetic - Cmax (Single Dosing)
|
104.9 ng/mL
Geometric Coefficient of Variation 32.2
|
117.6 ng/mL
Geometric Coefficient of Variation 34.0
|
259.3 ng/mL
Geometric Coefficient of Variation 73.5
|
111.1 ng/mL
Geometric Coefficient of Variation 52.2
|
SECONDARY outcome
Timeframe: From predose to 7 hours postdose on Cycle 2 Day 1Population: All patients in Phase 1b and patients at selected sites in Phase 2, who received at least one dose of HBI-8000 and had at least one postdose blood sample providing evaluable PK data for HBI-8000.
Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=2 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=3 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=4 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=4 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Pharmacokinetic - Cmax (Repeat Dosing)
|
NA ng/mL
Geometric Coefficient of Variation NA
Although individual values were observed, the statistical analysis plan (SAP) specified that only minimum and maximum would be presented and all other descriptive statistics (including geometric mean and geometric coefficient of variation) would be reported as NA for n=2.
|
112.8 ng/mL
Geometric Coefficient of Variation 93.8
|
228.6 ng/mL
Geometric Coefficient of Variation 72.9
|
96.79 ng/mL
Geometric Coefficient of Variation 55.9
|
SECONDARY outcome
Timeframe: From predose (0.5 hour prior to breakfast) to 7 hours postdose on Cycle 1 Day 1Population: All patients in Phase 1b and patients at selected sites in Phase 2, who received at least one dose of HBI-8000 and had at least one postdose blood sample providing evaluable PK data for HBI-8000.
Area under the plasma concentration time curve from zero (predose) to 7 hours postdose, calculated by linear up/log down trapezoidal summation.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=3 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=8 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Pharmacokinetic - AUC(0-7) (Single Dosing)
|
383.6 ng*h/mL
Geometric Coefficient of Variation 8.9
|
341.5 ng*h/mL
Geometric Coefficient of Variation 97.8
|
972.5 ng*h/mL
Geometric Coefficient of Variation 124.2
|
402.1 ng*h/mL
Geometric Coefficient of Variation 94.3
|
SECONDARY outcome
Timeframe: From predose to 7 hours postdose on Cycle 2 Day 1Population: All patients in Phase 1b and patients at selected sites in Phase 2, who received at least one dose of HBI-8000 and had at least one postdose blood sample providing evaluable PK data for HBI-8000.
Area under the plasma concentration time curve from zero (predose) to 7 hours postdose, calculated by linear up/log down trapezoidal summation.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=2 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=3 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=4 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=3 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Pharmacokinetic - AUC(0-7) (Repeat Dosing)
|
NA ng*h/mL
Geometric Coefficient of Variation NA
Although individual values were observed, the statistical analysis plan (SAP) specified that only minimum and maximum would be presented and all other descriptive statistics (including geometric mean and geometric coefficient of variation) would be reported as NA for n=2.
|
392.2 ng*h/mL
Geometric Coefficient of Variation 117.3
|
929.4 ng*h/mL
Geometric Coefficient of Variation 89.0
|
433.0 ng*h/mL
Geometric Coefficient of Variation 78.3
|
SECONDARY outcome
Timeframe: From predose (0.5 hour prior to breakfast) on Cycle 1 Day 1 to 24 hours on Cycle 1 Day 2 (no dose administered)Population: All subjects who received at least one dose of HBI 8000 and had at least one postdose blood sample providing evaluable PK data for HBI 8000.
Area under the plasma concentration time curve from zero (predose) to 24 hours postdose, calculated by linear up/log down trapezoidal summation. Calculated for C1D1 only.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=3 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=8 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Pharmacokinetic - AUC(0-24)
|
1590 ng*h/mL
Geometric Coefficient of Variation 29.7
|
1734 ng*h/mL
Geometric Coefficient of Variation 29.3
|
3690 ng*h/mL
Geometric Coefficient of Variation 54.9
|
1605 ng*h/mL
Geometric Coefficient of Variation 44.5
|
SECONDARY outcome
Timeframe: From predose (0.5 hour prior to breakfast) to 7 hours postdose on Cycle 1 Day 1, at 24 hours on Cycle 1 Day 2 (no dose administered)Population: All patients in Phase 1b and patients at selected sites in Phase 2, who received at least one dose of HBI-8000 and had at least one postdose blood sample providing evaluable PK data for HBI-8000.
Time of Cmax, obtained directly from the observed concentration versus time data.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=3 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=8 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Pharmacokinetic - Tmax (Single Dosing)
|
6.083 h
Standard Deviation 0.9393
|
11.054 h
Standard Deviation 9.4287
|
4.426 h
Standard Deviation 1.9682
|
6.715 h
Standard Deviation 6.5280
|
SECONDARY outcome
Timeframe: From predose to 24 hours postdose on Cycle 2 Day 1Population: All patients in Phase 1b and patients at selected sites in Phase 2, who received at least one dose of HBI-8000 and had at least one postdose blood sample providing evaluable PK data for HBI-8000.
Time of Cmax, obtained directly from the observed concentration versus time data.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=2 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=3 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=4 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
n=4 Participants
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Pharmacokinetic - Tmax (Repeat Dosing)
|
NA h
Standard Deviation NA
Although individual values were observed, the statistical analysis plan (SAP) specified that only minimum and maximum would be presented and all other descriptive statistics (including mean and standard deviation) would be reported as NA for n=2.
|
5.833 h
Standard Deviation 1.5190
|
5.613 h
Standard Deviation 2.3897
|
6.693 h
Standard Deviation 0.3244
|
SECONDARY outcome
Timeframe: 0 (predose) up to 4 hours postdose on C1D1 and C2D1Population: All subjects in Phase 1b, who had baseline Holter ECG measurements and at least 1 postdose Holter ECG measurement evaluable for pharmacodynamics.
Utilized a random coefficients mixed effects model for the change from baseline (ΔQTcF) values with continuous effects for HBI 8000 plasma concentration and baseline value (corrected for overall baseline mean), plus subject level random effects for intercept and concentration slope under unstructured covariance.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=3 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
QTcF Values >450 Msec
|
0 participants
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 0 (predose) up to 4 hours postdose on C1D1 and C2D1Population: All subjects in Phase 1b, who had baseline Holter ECG measurements and at least 1 postdose Holter ECG measurement evaluable for pharmacodynamics.
Utilized a random coefficients mixed effects model for the change from baseline (ΔQTcF) values with continuous effects for HBI 8000 plasma concentration and baseline value (corrected for overall baseline mean), plus subject level random effects for intercept and concentration slope under unstructured covariance.
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=3 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
n=6 Participants
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
n=7 Participants
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
QTcF Increase > 30 Msec
|
0 participants
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 0 (predose) up to 4 hours postdose on C1D1 and C2D1Population: All subjects in Phase 1b, who had baseline Holter ECG measurements and at least 1 postdose Holter ECG measurement evaluable for pharmacodynamics.
Slope estimate between ΔQTcF and HBI 8000 concentrations
Outcome measures
| Measure |
Phase 1b and 2 HBI-8000 30 mg: Melanoma
n=16 Participants
Melanoma patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
Phase 1/HBI-8000 30mg in Combination With Nivolumab
HBI-8000 dose 30mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1/HBI-8000 40mg in Combination With Nivolumab
HBI-8000 dose 40mg orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks
|
Phase 1b and 2 HBI-8000 30 mg: Total
All patients who treated at RP2D (30mg) of HBI-8000 in combination with nivolumab in the Phase 1b and 2
|
|---|---|---|---|---|
|
Concentration Slope
|
-0.02154 ms/mg/ml
Interval -0.03426 to -0.008814
|
—
|
—
|
—
|
Adverse Events
Phase 1b: HBI-8000 40 mg in Combination With Nivolumab
Serious events: 4 serious events
Other events: 7 other events
Deaths: 7 deaths
Phase 1b: HBI-8000 20 mg in Combination With Nivolumab
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Phase 1b: HBI-8000 30 mg in Combination With Nivolumab
Serious events: 6 serious events
Other events: 7 other events
Deaths: 4 deaths
Phase 2: HBI-8000 30 mg in Combination With Nivolumab
Serious events: 39 serious events
Other events: 79 other events
Deaths: 28 deaths
Serious adverse events
| Measure |
Phase 1b: HBI-8000 40 mg in Combination With Nivolumab
n=7 participants at risk
Phase 1b Cohort 3: HBI-8000 40 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 20 mg in Combination With Nivolumab
n=3 participants at risk
Phase 1b Cohort 1: HBI-8000 20 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 30 mg in Combination With Nivolumab
n=7 participants at risk
Phase 1b Cohort 2: HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 2: HBI-8000 30 mg in Combination With Nivolumab
n=79 participants at risk
HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing.
Nivolumab 240 mg was administered via intravenous infusions every 2 weeks or 480 mg was administered via intravenous infusions every 4 weeks.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Aortic valve disease
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Atrial fibrillation
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Cardiac arrest
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Colitis
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Generalised oedema
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Non-cardiac chest pain
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Systemic inflammatory response syndrome
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Biliary tract infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Bronchitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
COVID-19
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Cellulitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Influenza
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Pneumonia mycoplasmal
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Septic shock
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Amylase increased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Lipase increased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Somnolence
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Vascular disorders
Hypotension
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Vascular disorders
Vasculitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
Other adverse events
| Measure |
Phase 1b: HBI-8000 40 mg in Combination With Nivolumab
n=7 participants at risk
Phase 1b Cohort 3: HBI-8000 40 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 20 mg in Combination With Nivolumab
n=3 participants at risk
Phase 1b Cohort 1: HBI-8000 20 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 1b: HBI-8000 30 mg in Combination With Nivolumab
n=7 participants at risk
Phase 1b Cohort 2: HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing. Nivolumab 240 mg was administered via intravenous infusions every 2 weeks.
|
Phase 2: HBI-8000 30 mg in Combination With Nivolumab
n=79 participants at risk
HBI-8000 30 mg was administered orally twice weekly (BIW), approximately 30 minutes after a regular meal with 3-4 days between dosing.
Nivolumab 240 mg was administered via intravenous infusions every 2 weeks or 480 mg was administered via intravenous infusions every 4 weeks.
|
|---|---|---|---|---|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Eye disorders
Cataract
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Eye disorders
Episcleritis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Eye disorders
Eye pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Eye disorders
Vision blurred
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Constipation
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
25.3%
20/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Diarrhoea
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
66.7%
2/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
53.2%
42/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
16.5%
13/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
13.9%
11/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
17.7%
14/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Atrial fibrillation
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Cardiac failure
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Left atrial enlargement
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Mitral valve incompetence
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Palpitations
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Pericardial effusion
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Pulmonary valve incompetence
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Sinus tachycardia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
10.1%
8/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Tachycardia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Congenital, familial and genetic disorders
Keratosis follicular
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Ear and labyrinth disorders
Ear haemorrhage
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Endocrine disorders
Adrenal insufficiency
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Blood and lymphatic system disorders
Anaemia
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
46.8%
37/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
19.0%
15/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
29.1%
23/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Abdominal pain lower
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
11.4%
9/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Abdominal wall mass
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Colitis
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
10.1%
8/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Haemorrhoids
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Nausea
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
66.7%
2/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
55.7%
44/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
30.4%
24/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Catheter site bruise
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Catheter site pain
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Chills
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
12.7%
10/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Face oedema
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Fatigue
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
66.7%
2/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
71.4%
5/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
65.8%
52/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Influenza like illness
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Localised oedema
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Malaise
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Non-cardiac chest pain
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Oedema peripheral
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
36.7%
29/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Performance status decreased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
General disorders
Pyrexia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
11.4%
9/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Hepatobiliary disorders
Dilatation intrahepatic duct acquired
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Fungal skin infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Helicobacter infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Oral candidiasis
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Penile infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Septic shock
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
12.7%
10/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Contusion
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Fall
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Rib fracture
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Skin laceration
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Skin wound
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Alanine aminotransferase increased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
21.5%
17/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Amylase increased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
17.7%
14/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Aspartate aminotransferase increased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
13.9%
11/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Blood alkaline phosphatase increased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
17.7%
14/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Blood creatinine increased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
20.3%
16/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Blood thyroid stimulating hormone decreased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Blood thyroid stimulating hormone increased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Cardiac murmur
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Lipase increased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
24.1%
19/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Lymphocyte count decreased
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
30.4%
24/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Neutrophil count decreased
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
41.8%
33/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Occult blood positive
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Platelet count decreased
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
53.2%
42/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Thyroxine free decreased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Tri-iodothyronine free decreased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Tri-iodothyronine free increased
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Weight decreased
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
71.4%
5/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
35.4%
28/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
Weight increased
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Investigations
White blood cell count decreased
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
40.5%
32/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
39.2%
31/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Dehydration
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
30.4%
24/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
16.5%
13/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
32.9%
26/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
12.7%
10/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
36.7%
29/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
17.7%
14/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
22.8%
18/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
15.2%
12/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
31.6%
25/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
27.8%
22/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Dysgeusia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
19.0%
15/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
10.1%
8/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
22.8%
18/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
66.7%
2/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
13.9%
11/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Dysplastic naevus
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm skin
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Dizziness
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
20.3%
16/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Electric shock sensation
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Headache
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
25.3%
20/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Lethargy
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Muscle spasticity
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Post herpetic neuralgia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Nervous system disorders
Presyncope
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Psychiatric disorders
Agitation
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Psychiatric disorders
Anxiety
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
12.7%
10/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Psychiatric disorders
Depression
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
20.3%
16/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Renal and urinary disorders
Ketonuria
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Reproductive system and breast disorders
Oedema genital
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic sinusitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
27.8%
22/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
66.7%
2/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
57.1%
4/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
39.2%
31/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
13.9%
11/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
10.1%
8/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
10.1%
8/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
12.7%
10/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
13.9%
11/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiration abnormal
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
7.6%
6/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
3.8%
3/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
11.4%
9/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
6.3%
5/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
27.8%
22/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
1.3%
1/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
2.5%
2/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Skin and subcutaneous tissue disorders
Vitiligo
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
8.9%
7/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Surgical and medical procedures
Cholecystectomy
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Vascular disorders
Embolism
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
33.3%
1/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Vascular disorders
Hot flush
|
0.00%
0/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
14.3%
1/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
5.1%
4/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
|
Vascular disorders
Hypotension
|
42.9%
3/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
0.00%
0/3 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
28.6%
2/7 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
15.2%
12/79 • From the first dose of study treatment until end of safety follow-up, up to 5 years 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place