Trial Outcomes & Findings for Phase I/Ib Study of Pembrolizumab With Vorinostat for Patients With Advanced Renal or Urothelial Cell Carcinoma (NCT NCT02619253)
NCT ID: NCT02619253
Last Updated: 2024-11-18
Results Overview
Measured by RECIST v1.1 Complete response: Disappearance of all target lesions Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter The percentage of patients with objective response and its 95% confidence interval will be provided.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
52 participants
Primary outcome timeframe
Up to 4.5 years
Results posted on
2024-11-18
Participant Flow
Participant milestones
| Measure |
Dose Finding Cohort Dose Level 1
Patients were treated with 100 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Dose Finding Cohort Dose Level 2
Patients were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Expansion Cohort A
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
15
|
14
|
15
|
|
Overall Study
COMPLETED
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
4
|
4
|
14
|
14
|
15
|
Reasons for withdrawal
| Measure |
Dose Finding Cohort Dose Level 1
Patients were treated with 100 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Dose Finding Cohort Dose Level 2
Patients were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Expansion Cohort A
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
1
|
3
|
|
Overall Study
Alternative Therapy
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Death
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Disease Progression
|
4
|
2
|
8
|
9
|
10
|
|
Overall Study
Needed a disqualifying therapy
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Transferred to hospice
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
2
|
3
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
2
|
Baseline Characteristics
Phase I/Ib Study of Pembrolizumab With Vorinostat for Patients With Advanced Renal or Urothelial Cell Carcinoma
Baseline characteristics by cohort
| Measure |
Dose Finding Cohort Dose Level 1
n=4 Participants
Patients were treated with 100 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Dose Finding Cohort Dose Level 2
n=4 Participants
Patients were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Expansion Cohort A
n=15 Participants
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=14 Participants
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
n=15 Participants
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
15 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
14 Participants
n=36 Participants
|
37 Participants
n=10 Participants
|
|
Age, Continuous
|
66.2 years
STANDARD_DEVIATION 12.4 • n=93 Participants
|
69.3 years
STANDARD_DEVIATION 7.8 • n=4 Participants
|
64.3 years
STANDARD_DEVIATION 8.6 • n=27 Participants
|
65.4 years
STANDARD_DEVIATION 10.3 • n=483 Participants
|
69.0 years
STANDARD_DEVIATION 6.5 • n=36 Participants
|
66.5 years
STANDARD_DEVIATION 8.7 • n=10 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
11 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
10 Participants
n=483 Participants
|
15 Participants
n=36 Participants
|
41 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
3 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
13 Participants
n=483 Participants
|
15 Participants
n=36 Participants
|
49 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
14 Participants
n=483 Participants
|
13 Participants
n=36 Participants
|
48 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=93 Participants
|
4 participants
n=4 Participants
|
15 participants
n=27 Participants
|
14 participants
n=483 Participants
|
15 participants
n=36 Participants
|
52 participants
n=10 Participants
|
|
ECOG Performance Status
0
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
16 Participants
n=10 Participants
|
|
ECOG Performance Status
1
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
10 Participants
n=36 Participants
|
33 Participants
n=10 Participants
|
|
ECOG Performance Status
2
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
ECOG Performance Status
Missing
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Up to 4.5 yearsPopulation: Patients were considered eligible for this analysis if they were in the expansion cohorts and had at least one follow-up assessment of disease status after completing one cycle of combination therapy.
Measured by RECIST v1.1 Complete response: Disappearance of all target lesions Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter The percentage of patients with objective response and its 95% confidence interval will be provided.
Outcome measures
| Measure |
Expansion Cohort A
n=13 Participants
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=11 Participants
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
n=12 Participants
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Objective Response Rate (Percentage of Patients With Complete Response or Partial Response)
|
7.7 percentage of participants
Interval 0.2 to 36.0
|
0 percentage of participants
Interval 0.0 to 28.5
|
16.7 percentage of participants
Interval 2.1 to 48.4
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 4.5 yearsPopulation: Patients were considered eligible for this analysis if they were in the expansion cohorts and had at least one follow-up assessment of disease status after completing one cycle of combination therapy.
Progression free survival was determined from start date of treatment to date of progression for patients who progressed or date of death for patients who died without progressing. The observations of patients remaining alive and progression free were censored at the date of last disease evaluation. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Outcome measures
| Measure |
Expansion Cohort A
n=13 Participants
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=11 Participants
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
n=12 Participants
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Progression Free Survival
|
2.9 months
Interval 1.3 to 21.8
|
3.5 months
Interval 2.5 to 7.2
|
3.5 months
Interval 1.3 to 7.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 4.5 yearsPopulation: Patients who received at least one dose of either study drug.
Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event with grade 3 or greater using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Outcome measures
| Measure |
Expansion Cohort A
n=4 Participants
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=4 Participants
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
n=15 Participants
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=14 Participants
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
n=15 Participants
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Safety and Tolerablity: Number of Patients Who Experienced Grade 3 or 4 Adverse Events
|
0 Participants
|
0 Participants
|
5 Participants
|
3 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Patients who completed one cycle of study therapy.
Dose limiting toxicities (DLTs) are defined as Grade ≥ 3 hematological/non hematological toxicities attributable to vorinostat and/or pembrolizumab during the first 21 days of the combination treatment (days 1-21). If DLTs occur in 1 patient treated at the starting dose level a minimum of another 3 patients will be treated at this dose level. If a DLT occurs in more than 1 patient in the first 6 patients the study will be terminated. If a DLT occurs in \< 1/3 patients or ≤ 1/6 patients, 3 additional patients will be treated at the next dose level (level 2) with 200 mg vorinostat PO. If no DLTs occur at dose level 2, this dose level will be recommended for the expansion cohorts of the study.
Outcome measures
| Measure |
Expansion Cohort A
n=3 Participants
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=3 Participants
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Number of Patients Experiencing a Dose Limiting Toxicity
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
Adverse Events
Dose Finding Cohort Dose Level 1
Serious events: 3 serious events
Other events: 4 other events
Deaths: 4 deaths
Dose Finding Cohort Dose Level 2
Serious events: 2 serious events
Other events: 4 other events
Deaths: 4 deaths
Expansion Cohort A
Serious events: 10 serious events
Other events: 15 other events
Deaths: 11 deaths
Expansion Cohort B
Serious events: 6 serious events
Other events: 13 other events
Deaths: 13 deaths
Expansion Cohort C
Serious events: 5 serious events
Other events: 14 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Dose Finding Cohort Dose Level 1
n=4 participants at risk
Patients were treated with 100 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Dose Finding Cohort Dose Level 2
n=4 participants at risk
Patients were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Expansion Cohort A
n=15 participants at risk
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=14 participants at risk
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
n=15 participants at risk
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 3 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Death NOS
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Nervous system disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Infections and infestations
Sepsis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Fever
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Endocrine disorders
Hyperthyroidism
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Infections and infestations
Joint infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Localized edema
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Pain
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Stroke
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
Other adverse events
| Measure |
Dose Finding Cohort Dose Level 1
n=4 participants at risk
Patients were treated with 100 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Dose Finding Cohort Dose Level 2
n=4 participants at risk
Patients were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had either previously treated, progressive renal or urothelial cell carcinoma that was locally advanced or metastatic, or progressive prostate cancer that was locally advanced or metastatic.
|
Expansion Cohort A
n=15 participants at risk
Patients with anti-PD1 naïve renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort B
n=14 participants at risk
Patients with anti-PD1 resistant renal and urothelial cell carcinoma were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have previously undergone cancer treatment and have progressive disease that was locally advanced or metastatic.
|
Expansion Cohort C
n=15 participants at risk
Patients with androgen-sensitive or castration-resistant prostate cancer were treated with 200 mg of oral vorinostat every day for 14 days, and with pembrolizumab at the fixed dose of 200 mg IV on day one of each cycle. Each cycle lasted 21 days. Patients had to have progressive disease that was locally advanced or metastatic.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
50.0%
2/4 • Number of events 4 • Up to 4.5 years
|
50.0%
2/4 • Number of events 7 • Up to 4.5 years
|
66.7%
10/15 • Number of events 16 • Up to 4.5 years
|
14.3%
2/14 • Number of events 4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 8 • Up to 4.5 years
|
|
General disorders
Fatigue
|
50.0%
2/4 • Number of events 5 • Up to 4.5 years
|
25.0%
1/4 • Number of events 3 • Up to 4.5 years
|
73.3%
11/15 • Number of events 18 • Up to 4.5 years
|
28.6%
4/14 • Number of events 6 • Up to 4.5 years
|
40.0%
6/15 • Number of events 6 • Up to 4.5 years
|
|
Gastrointestinal disorders
Nausea
|
75.0%
3/4 • Number of events 4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
66.7%
10/15 • Number of events 14 • Up to 4.5 years
|
42.9%
6/14 • Number of events 7 • Up to 4.5 years
|
66.7%
10/15 • Number of events 10 • Up to 4.5 years
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
75.0%
3/4 • Number of events 3 • Up to 4.5 years
|
26.7%
4/15 • Number of events 12 • Up to 4.5 years
|
14.3%
2/14 • Number of events 2 • Up to 4.5 years
|
53.3%
8/15 • Number of events 14 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
50.0%
2/4 • Number of events 2 • Up to 4.5 years
|
25.0%
1/4 • Number of events 3 • Up to 4.5 years
|
53.3%
8/15 • Number of events 9 • Up to 4.5 years
|
28.6%
4/14 • Number of events 6 • Up to 4.5 years
|
26.7%
4/15 • Number of events 5 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Anorexia
|
75.0%
3/4 • Number of events 4 • Up to 4.5 years
|
50.0%
2/4 • Number of events 2 • Up to 4.5 years
|
46.7%
7/15 • Number of events 8 • Up to 4.5 years
|
35.7%
5/14 • Number of events 6 • Up to 4.5 years
|
26.7%
4/15 • Number of events 4 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
25.0%
1/4 • Number of events 2 • Up to 4.5 years
|
25.0%
1/4 • Number of events 3 • Up to 4.5 years
|
46.7%
7/15 • Number of events 10 • Up to 4.5 years
|
28.6%
4/14 • Number of events 5 • Up to 4.5 years
|
20.0%
3/15 • Number of events 4 • Up to 4.5 years
|
|
Vascular disorders
Hypertension
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 21 • Up to 4.5 years
|
14.3%
2/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Vomiting
|
75.0%
3/4 • Number of events 4 • Up to 4.5 years
|
50.0%
2/4 • Number of events 3 • Up to 4.5 years
|
33.3%
5/15 • Number of events 7 • Up to 4.5 years
|
21.4%
3/14 • Number of events 4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
46.7%
7/15 • Number of events 11 • Up to 4.5 years
|
14.3%
2/14 • Number of events 3 • Up to 4.5 years
|
26.7%
4/15 • Number of events 5 • Up to 4.5 years
|
|
Infections and infestations
Urinary tract infection
|
75.0%
3/4 • Number of events 5 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 8 • Up to 4.5 years
|
7.1%
1/14 • Number of events 3 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Investigations
Creatinine increased
|
0.00%
0/4 • Up to 4.5 years
|
50.0%
2/4 • Number of events 3 • Up to 4.5 years
|
20.0%
3/15 • Number of events 8 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
26.7%
4/15 • Number of events 15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Pain
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
13.3%
2/15 • Number of events 4 • Up to 4.5 years
|
14.3%
2/14 • Number of events 3 • Up to 4.5 years
|
20.0%
3/15 • Number of events 6 • Up to 4.5 years
|
|
Gastrointestinal disorders
Constipation
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
40.0%
6/15 • Number of events 6 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
26.7%
4/15 • Number of events 5 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 3 • Up to 4.5 years
|
7.1%
1/14 • Number of events 3 • Up to 4.5 years
|
20.0%
3/15 • Number of events 7 • Up to 4.5 years
|
|
General disorders
Fever
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
20.0%
3/15 • Number of events 4 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
20.0%
3/15 • Number of events 6 • Up to 4.5 years
|
|
Nervous system disorders
Headache
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 6 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
26.7%
4/15 • Number of events 4 • Up to 4.5 years
|
|
General disorders
Edema limbs
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
26.7%
4/15 • Number of events 6 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 7 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Endocrine disorders
Hypothyroidism
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
14.3%
2/14 • Number of events 4 • Up to 4.5 years
|
33.3%
5/15 • Number of events 5 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
26.7%
4/15 • Number of events 8 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
40.0%
6/15 • Number of events 8 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
20.0%
3/15 • Number of events 8 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
25.0%
1/4 • Number of events 2 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.0%
1/4 • Number of events 2 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 3 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 6 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Investigations
Platelet count decreased
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
14.3%
2/14 • Number of events 3 • Up to 4.5 years
|
13.3%
2/15 • Number of events 4 • Up to 4.5 years
|
|
Investigations
Weight loss
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
20.0%
3/15 • Number of events 4 • Up to 4.5 years
|
14.3%
2/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
21.4%
3/14 • Number of events 4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
21.4%
3/14 • Number of events 3 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Vascular disorders
Hypotension
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
26.7%
4/15 • Number of events 4 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
General disorders
Chills
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
20.0%
3/15 • Number of events 3 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Gastrointestinal disorders
Dry mouth
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Nervous system disorders
Dysgeusia
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Eye disorders
Blurred vision
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 4 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Edema face
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/4 • Up to 4.5 years
|
50.0%
2/4 • Number of events 2 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/4 • Up to 4.5 years
|
50.0%
2/4 • Number of events 2 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Infections and infestations
Papulopustular rash
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
13.3%
2/15 • Number of events 4 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Infections and infestations
Sinusitis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 3 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
|
Infections and infestations
Skin infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 4 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 3 • Up to 4.5 years
|
|
Psychiatric disorders
Anxiety
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
14.3%
2/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Flu like symptoms
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 3 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Cardiac disorders
Sinus tachycardia
|
50.0%
2/4 • Number of events 2 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Investigations
Blood bilirubin increased
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Psychiatric disorders
Depression
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Endocrine disorders
Endocrine disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Vascular disorders
Hot flashes
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Endocrine disorders
Hyperthyroidism
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
General disorders
Infusion related reaction
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
13.3%
2/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Reproductive system and breast disorders
Penile pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 2 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Renal and urinary disorders
Urinary frequency
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 2 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Psychiatric disorders
Agitation
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Gastrointestinal disorders
Anal hemorrhage
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Nervous system disorders
Ataxia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Infections and infestations
Bladder infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Reproductive system and breast disorders
Breast pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Investigations
Cardiac troponin I increased
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Investigations
Cholesterol high
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Eye disorders
Dry eye
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Duodenal obstruction
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Eye disorders
Eye disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Cardiac disorders
Heart failure
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Vascular disorders
Hematoma
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Infections and infestations
Infections and infestations - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Investigations
Investigations - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Infections and infestations
Lip infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Infections and infestations
Lung infection
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Movements involuntary
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness trunk
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Nervous system disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
25.0%
1/4 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Infections and infestations
Penile infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Infections and infestations
Peritoneal infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Presyncope
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Sinus disorder
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Skin induration
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
7.1%
1/14 • Number of events 1 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
|
Infections and infestations
Wound infection
|
0.00%
0/4 • Up to 4.5 years
|
0.00%
0/4 • Up to 4.5 years
|
6.7%
1/15 • Number of events 1 • Up to 4.5 years
|
0.00%
0/14 • Up to 4.5 years
|
0.00%
0/15 • Up to 4.5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place