Trial Outcomes & Findings for Dose-escalation Study of Birinapant and Pembrolizumab in Solid Tumors (NCT NCT02587962)
NCT ID: NCT02587962
Last Updated: 2021-01-14
Results Overview
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through blood pressure.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
34 participants
Primary outcome timeframe
Baseline and up to 2 yrs (follow-up)
Results posted on
2021-01-14
Participant Flow
Participant milestones
| Measure |
Phase 1 - 5.6 mg
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
6
|
7
|
15
|
|
Overall Study
COMPLETED
|
1
|
0
|
0
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
6
|
6
|
15
|
Reasons for withdrawal
| Measure |
Phase 1 - 5.6 mg
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
1
|
4
|
|
Overall Study
Radiological progression
|
2
|
2
|
2
|
5
|
10
|
|
Overall Study
Clinical progression
|
0
|
1
|
2
|
0
|
1
|
Baseline Characteristics
Dose-escalation Study of Birinapant and Pembrolizumab in Solid Tumors
Baseline characteristics by cohort
| Measure |
Total
n=34 Participants
Total of all reporting groups
|
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 - 22 mg
n=15 Participants
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
60.08 years
STANDARD_DEVIATION 9.50 • n=10 Participants
|
56 years
STANDARD_DEVIATION 16.09 • n=5 Participants
|
71.3 years
STANDARD_DEVIATION 3.21 • n=7 Participants
|
60.2 years
STANDARD_DEVIATION 6.15 • n=5 Participants
|
59.1 years
STANDARD_DEVIATION 11.61 • n=4 Participants
|
53.8 years
STANDARD_DEVIATION 10.43 • n=21 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=10 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=10 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
2 Participants
n=10 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
30 Participants
n=10 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
2 Participants
n=10 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
34 participants
n=10 Participants
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
7 participants
n=4 Participants
|
15 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through blood pressure.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Blood Pressure (Safety and Tolerability in the Dose Escalation Phase)
Systolic blood pressure at baseline
|
137.3 mmHg
Standard Deviation 18.6
|
143.3 mmHg
Standard Deviation 14.5
|
134.0 mmHg
Standard Deviation 22.1
|
118.6 mmHg
Standard Deviation 11.4
|
—
|
|
Blood Pressure (Safety and Tolerability in the Dose Escalation Phase)
Systolic blood pressure at follow-up
|
120.0 mmHg
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
107.0 mmHg
Standard Deviation 1.4
|
119.7 mmHg
Standard Deviation 30.2
|
120.0 mmHg
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
—
|
|
Blood Pressure (Safety and Tolerability in the Dose Escalation Phase)
Diastolic blood pressure at baseline
|
78.0 mmHg
Standard Deviation 2.0
|
77.0 mmHg
Standard Deviation 15.5
|
74.3 mmHg
Standard Deviation 9.3
|
66.6 mmHg
Standard Deviation 7.9
|
—
|
|
Blood Pressure (Safety and Tolerability in the Dose Escalation Phase)
Diastolic blood pressure at follow-up
|
84.0 mmHg
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
66.0 mmHg
Standard Deviation 8.5
|
71.3 mmHg
Standard Deviation 11.4
|
75.0 mmHg
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
—
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through electrocardiogram.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Electrocardiogram: QT Interval (Safety and Tolerability in the Dose Escalation Phase)
Electrocardiogram QT interval at baseline
|
368.7 ms
Standard Deviation 30.6
|
388.3 ms
Standard Deviation 11.2
|
386.3 ms
Standard Deviation 32.9
|
365.9 ms
Standard Deviation 32.7
|
—
|
|
Electrocardiogram: QT Interval (Safety and Tolerability in the Dose Escalation Phase)
Electrocardiogram QT interval at follow-up
|
392.0 ms
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
—
|
380.0 ms
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
364.0 ms
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
—
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through amylase and lipase.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Amylase and Lipase (Safety and Tolerability in the Dose Escalation Phase)
Amylase at baseline
|
33.7 U/L
Standard Deviation 32.5
|
38.3 U/L
Standard Deviation 9.0
|
64.3 U/L
Standard Deviation 8.0
|
40.6 U/L
Standard Deviation 27.4
|
—
|
|
Amylase and Lipase (Safety and Tolerability in the Dose Escalation Phase)
Amylase at follow-up
|
27.0 U/L
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
49.0 U/L
Standard Deviation 41.0
|
56.5 U/L
Standard Deviation 38.9
|
60.0 U/L
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
—
|
|
Amylase and Lipase (Safety and Tolerability in the Dose Escalation Phase)
Lipase at baseline
|
17.0 U/L
Standard Deviation 12.2
|
24.0 U/L
Standard Deviation 21.0
|
32.2 U/L
Standard Deviation 21.4
|
49.9 U/L
Standard Deviation 63.3
|
—
|
|
Amylase and Lipase (Safety and Tolerability in the Dose Escalation Phase)
Lipase at follow-up
|
12.0 U/L
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
15.5 U/L
Standard Deviation 10.6
|
16.0 U/L
Standard Deviation 2.8
|
18.0 U/L
Standard Deviation NA
Only 1 participant assessed at follow-up.
|
—
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through thyroxine free.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Thyroxine Free (Safety and Tolerability in the Dose Escalation Phase)
Thyroxine free at baseline
|
16.8 nmol/L
Standard Deviation 5.0
|
15.0 nmol/L
Standard Deviation 3.0
|
15.0 nmol/L
Standard Deviation 3.3
|
18.7 nmol/L
Standard Deviation 1.6
|
—
|
|
Thyroxine Free (Safety and Tolerability in the Dose Escalation Phase)
Thyroxine free at last assessment
|
25.2 nmol/L
Standard Deviation 8.0
|
16.7 nmol/L
Standard Deviation 5.4
|
16.9 nmol/L
Standard Deviation 4.1
|
16.5 nmol/L
Standard Deviation 3.6
|
—
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through Thyrotropin.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Thyrotropin (Safety and Tolerability in the Dose Escalation Phase)
Thyrotropin at baseline
|
3.8 mU/L
Standard Deviation 3.2
|
2.4 mU/L
Standard Deviation 0.9
|
1.7 mU/L
Standard Deviation 0.8
|
1.4 mU/L
Standard Deviation 0.9
|
—
|
|
Thyrotropin (Safety and Tolerability in the Dose Escalation Phase)
Thyrotropin at last assessment
|
14.2 mU/L
Standard Deviation 18.7
|
7.7 mU/L
Standard Deviation 4.0
|
2.3 mU/L
Standard Deviation 1.3
|
2.6 mU/L
Standard Deviation 2.1
|
—
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through hemoglobin.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Hemoglobin (Safety and Tolerability in the Dose Escalation Phase)
Hemoglobin at baseline
|
110.3 g/L
Standard Deviation 20.2
|
107.3 g/L
Standard Deviation 8.6
|
112.0 g/L
Standard Deviation 11.8
|
102.0 g/L
Standard Deviation 16.0
|
—
|
|
Hemoglobin (Safety and Tolerability in the Dose Escalation Phase)
Hemoglobin at follow-up
|
89.0 g/L
Standard Deviation NA
Only 1 participant was assessed at follow-up
|
107.0 g/L
Standard Deviation 14.1
|
116.0 g/L
Standard Deviation 19.8
|
99.0 g/L
Standard Deviation NA
Only 1 participant was assessed at follow-up
|
—
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant when given in combination with pembrolizumab assessed through physical exam.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Physical Exam (Safety and Tolerability in the Dose Escalation Phase)
Clinically significant physical exam abnormalities - baseline
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
|
Physical Exam (Safety and Tolerability in the Dose Escalation Phase)
Clinically significant physical exam abnormalities - last assessment
|
0 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: For phase 2, only the colorectal cancer (CRC) cohort was analyzed for overall response rate. Patients were not recruited to the ovarian cancer or cervical cancer cohorts due to early termination of the study.
Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. A responder was a patient who showed best overall response of complete response (CR, disappearance of all target lesions) or partial response (PR, ≥30% decrease in the sum of the longest diameter of target lesions), which was confirmed again at least 4 weeks after the initial assessment.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
n=15 Participants
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Overall Response (Applicable for: Dose Escalation Phase and Dose Expansion Phase in Cohorts of Colorectal Cancer, Ovarian Cancer and Cervical Cancer)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Every 9 weeks; up to 2 yrsAnalysis of progression-free survival (PFS); time to progression, where progressive disease (PD) corresponds to ≥20% increase in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=3 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 Participants
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 Participants
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 Participants
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
n=15 Participants
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Tumor Response Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1:
|
15.4 Weeks
Interval 11.3 to
Due to low number of patients / lack of data, the upper inter-quartile could not be calculated.
|
7.7 Weeks
Interval 4.0 to 9.6
|
8.6 Weeks
Interval 8.0 to 26.0
|
8.0 Weeks
Interval 4.1 to 8.9
|
9.0 Weeks
Interval 8.1 to 18.1
|
SECONDARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant at the recommended phase 2 dose (RP2D) when given in combination with pembrolizumab assessed through blood pressure.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=15 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Blood Pressure (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Systolic blood pressure at baseline
|
130.9 mmHg
Standard Deviation 20.3
|
—
|
—
|
—
|
—
|
|
Blood Pressure (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Systolic blood pressure at follow-up
|
129.3 mmHg
Standard Deviation 16.6
|
—
|
—
|
—
|
—
|
|
Blood Pressure (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Diastolic blood pressure at baseline
|
80.0 mmHg
Standard Deviation 8.0
|
—
|
—
|
—
|
—
|
|
Blood Pressure (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Diastolic blood pressure at follow-up
|
74.4 mmHg
Standard Deviation 12.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant at the recommended phase 2 dose (RP2D) when given in combination with pembrolizumab assessed through electrocardiogram.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=15 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Electrocardiogram: QT Interval (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Electrocardiogram QT interval at baseline
|
383.5 ms
Standard Deviation 25.6
|
—
|
—
|
—
|
—
|
|
Electrocardiogram: QT Interval (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Electrocardiogram QT interval at follow-up
|
392.6 ms
Standard Deviation 38.7
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant at the recommended phase 2 dose (RP2D) when given in combination with pembrolizumab assessed through amylase and lipase.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=15 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Amylase and Lipase (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Lipase at baseline
|
44.3 U/L
Standard Deviation 41.1
|
—
|
—
|
—
|
—
|
|
Amylase and Lipase (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Lipase at follow-up
|
29.7 U/L
Standard Deviation 16.6
|
—
|
—
|
—
|
—
|
|
Amylase and Lipase (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Amylase at baseline
|
68.9 U/L
Standard Deviation 22.5
|
—
|
—
|
—
|
—
|
|
Amylase and Lipase (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Amylase at follow-up
|
93.0 U/L
Standard Deviation 35.4
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant at the recommended phase 2 dose (RP2D) when given in combination with pembrolizumab assessed through thyroxine free.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=15 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Thyroxine Free (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Thyroxine free at baseline
|
14.7 nmol/L
Standard Deviation 3.1
|
—
|
—
|
—
|
—
|
|
Thyroxine Free (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Thyroxine free at last assessment
|
16.4 nmol/L
Standard Deviation 4.4
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant at the recommended phase 2 dose (RP2D) when given in combination with pembrolizumab assessed through thyrotropin.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=15 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Thyrotropin (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Thyrotropin at baseline
|
2.3 mU/L
Standard Deviation 1.3
|
—
|
—
|
—
|
—
|
|
Thyrotropin (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Thyrotropin at last assessment
|
9.8 mU/L
Standard Deviation 23.5
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of birinapant at the recommended phase 2 dose (RP2D) when given in combination with pembrolizumab assessed through hemoglobin.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=15 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Hemoglobin (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Hemoglobin at baseline
|
126.4 g/L
Standard Deviation 15.4
|
—
|
—
|
—
|
—
|
|
Hemoglobin (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Hemoglobin at follow-up
|
130.2 g/L
Standard Deviation 13.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: As the population of participants were very ill, assessments outside clinical praxis were sometimes not performed.
Evaluation of the safety and tolerability of the RP2D of birinapant when given in combination with pembrolizumab assessed through physical exam.
Outcome measures
| Measure |
Phase 1 - 5.6 mg
n=15 Participants
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort.
|
|---|---|---|---|---|---|
|
Physical Exam (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Clinically significant physical exam abnormalities - baseline
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Physical Exam (Safety and Tolerability in the Dose Expansion Phase - Colorectal Cancer Cohort)
Clinically significant physical exam abnormalities - last assessment
|
2 Participants
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: Tumor activity according to iRECIST was not analyzed due to early termination of the study.
To be evaluated according to immune response evaluation criteria in solid tumors (iRECIST)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 through Day 8Population: Biomarkers in blood were not analyzed due to early termination of the study.
Measured by inhibitor of apoptosis proteins (IAPs), cytokines, tumor infiltrating lymphocytes (TILs) cluster of differentiation (CD)3, CD4, CD8, and CD19 as well as absolute neutrophil and lymphocyte counts
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and up to 2 yrs (follow-up)Population: Biomarkers in tumor biopsy samples were not analyzed due to early termination of the study.
Measured by: Programmed death ligand 1 (PD-1L), programmed cell death protein 1 receptor (PD-1) and related proteins, genome analysis, IAP gene copy number and TILs cluster of differentiation (CD)3, CD4, CD8 and CD19
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 through Day 8Population: Birinapant pharmacokinetics was not analyzed due to early termination of the study.
The plasma concentrations of birinapant was to be measured and summarized descriptively
Outcome measures
Outcome data not reported
Adverse Events
Phase 1 - 5.6 mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 1 - 11 mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 1 - 17 mg
Serious events: 4 serious events
Other events: 6 other events
Deaths: 1 deaths
Phase 1 - 22 mg
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Phase 2 CRC - 22 mg
Serious events: 5 serious events
Other events: 15 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Phase 1 - 5.6 mg
n=3 participants at risk
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 participants at risk
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 participants at risk
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 participants at risk
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
n=15 participants at risk
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
1/3 • Number of events 2 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Transient ischaemic attack
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
General disorders
Pyrexia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
General disorders
Death
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
General disorders
Asthenia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Infections and infestations
Sepsis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant ascites
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Infections and infestations
Pneumonitis bacterial
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Hepatobiliary disorders
Portal hypertension
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Smal intestinal obstruction
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
20.0%
3/15 • Number of events 3 • Up to 2 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 2 • Up to 2 years
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Duodenal perforation
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
Other adverse events
| Measure |
Phase 1 - 5.6 mg
n=3 participants at risk
Dose escalation (Phase 1): 5.6 mg birinapant + pembrolizumab
|
Phase 1 - 11 mg
n=3 participants at risk
Dose escalation (Phase 1): 11 mg birinapant + pembrolizumab
|
Phase 1 - 17 mg
n=6 participants at risk
Dose escalation (Phase 1): 17 mg birinapant + pembrolizumab
|
Phase 1 - 22 mg
n=7 participants at risk
Dose escalation (Phase 1): 22 mg birinapant + pembrolizumab
|
Phase 2 CRC - 22 mg
n=15 participants at risk
Dose expansion (Phase 2): 22 mg birinapant + pembrolizumab in colorectal cancer cohort
|
|---|---|---|---|---|---|
|
Vascular disorders
Hypotension
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
28.6%
2/7 • Number of events 2 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
General disorders
Pyrexia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Infections and infestations
Gingivitis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 3 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Infections and infestations
Skin infection
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Psychiatric disorders
Anxiety
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
20.0%
3/15 • Number of events 3 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
40.0%
6/15 • Number of events 6 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Vascular disorders
Hypertension
|
33.3%
1/3 • Number of events 2 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Increased bronchial secretion
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Psychiatric disorders
Insomnia
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Investigations
Lipase increased
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 4 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
33.3%
5/15 • Number of events 8 • Up to 2 years
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
20.0%
3/15 • Number of events 3 • Up to 2 years
|
|
Investigations
Weight decreased
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Amnesia
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
1/3 • Number of events 3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 5 • Up to 2 years
|
28.6%
2/7 • Number of events 4 • Up to 2 years
|
26.7%
4/15 • Number of events 7 • Up to 2 years
|
|
Investigations
Weight increased
|
66.7%
2/3 • Number of events 2 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Erythema
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Infections and infestations
Pharyngitis streptococcal
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
33.3%
5/15 • Number of events 5 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
28.6%
2/7 • Number of events 2 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Infections and infestations
Upper respiratory tract infection
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
28.6%
2/7 • Number of events 2 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Investigations
Blood creatinine increased
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
33.3%
5/15 • Number of events 6 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/3 • Up to 2 years
|
33.3%
1/3 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 2 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
20.0%
3/15 • Number of events 4 • Up to 2 years
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Gastric hypomotility
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Pancreatic failure
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 4 • Up to 2 years
|
42.9%
3/7 • Number of events 8 • Up to 2 years
|
20.0%
3/15 • Number of events 4 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Intertrigo
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
14.3%
1/7 • Number of events 4 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
14.3%
1/7 • Number of events 3 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
42.9%
3/7 • Number of events 4 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 2 • Up to 2 years
|
28.6%
2/7 • Number of events 2 • Up to 2 years
|
20.0%
3/15 • Number of events 3 • Up to 2 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 3 • Up to 2 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 2 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
13.3%
2/15 • Number of events 3 • Up to 2 years
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Eye disorders
Dry eye
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Eye disorders
Eye pain
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
General disorders
Fatigue
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
26.7%
4/15 • Number of events 8 • Up to 2 years
|
|
Eye disorders
Foreign body sensation in eye
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Endocrine disorders
Goitre
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Vascular disorders
Hot flush
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Hyposmia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Lip swelling
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Madarosis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
General disorders
Peripheral swelling
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 3 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Eye disorders
Photophobia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Eye disorders
Vision blurred
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
33.3%
2/6 • Number of events 3 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Vascular disorders
Bloody discharge
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
General disorders
Mucosal inflammation
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 2 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
General disorders
Oedema peripheral
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
13.3%
2/15 • Number of events 3 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 5 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
13.3%
2/15 • Number of events 3 • Up to 2 years
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
28.6%
2/7 • Number of events 2 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Investigations
Hyperbilirubinaemia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Metabolism and nutrition disorders
Abnormal loss of weight
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
13.3%
2/15 • Number of events 5 • Up to 2 years
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Renal and urinary disorders
Renal injury
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
0.00%
0/15 • Up to 2 years
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
14.3%
1/7 • Number of events 1 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Investigations
Amylase increased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
33.3%
5/15 • Number of events 11 • Up to 2 years
|
|
Gastrointestinal disorders
Chapped lips
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 2 • Up to 2 years
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
33.3%
5/15 • Number of events 5 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
General disorders
Chills
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
13.3%
2/15 • Number of events 2 • Up to 2 years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 4 • Up to 2 years
|
|
Vascular disorders
Venous thrombosis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Vascular disorders
Flushing
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant ascites
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Investigations
Thyroxine free decreased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Metabolism and nutrition disorders
Appetite disorder
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 2 • Up to 2 years
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus discomfort
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Endocrine disorders
Thyroiditis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Investigations
Platelet count decreased
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Anal incontinence
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Infections and infestations
Oral herpes
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
|
General disorders
Pain
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 2 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/3 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/7 • Up to 2 years
|
6.7%
1/15 • Number of events 1 • Up to 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Investigator must submit any proposed publication or presentation to the Sponsor, along with information about the scientific journal or presentation forum, at least 30 days before submission of the publication or presentation (2 weeks for abstracts). The Investigator will comply with Sponsor requests to delete confidential information (other than the study results) and to withhold publication or presentation for an additional 60 days in order to obtain patent protection if necessary.
- Publication restrictions are in place
Restriction type: OTHER