Study of the JAK Inhibitor Ruxolitinib Administered Orally to Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera-Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia-Myelofibrosis (PET-MF)
Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT01317875
Collaborator
Novartis (Industry)
69
18
2
105
3.8
0
Study Details
Study Description
Brief Summary
This is a Phase IB, open-label, dose-finding study of the JAK 1 and 2 inhibitor ruxolitinib in patients with myelofibrosis (MF). The study consists of two periods: the core study period, comprising the dose escalation stage and the safety extension phase up to Week 24, then the extension study period beyond Week 24 and up to 3 years, to further characterize the safety and efficacy of ruxolitinib in this patient population. The dose escalation phase will enroll successive cohorts of patients who receive increasing doses of ruxolitinib until the maximum safe starting dose (MSSD) is determined. In the safety expansion phase, additional patients will be treated with ruxolitinib at the MSSD defined during dose escalation. The primary objective is to establish the MSSD of ruxolitinib in patients with MF and starting platelet counts < 100 x 10 ^9/L
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
69 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib, Open-label, Dose-finding Study of the JAK Inhibitor INC424 Tablets Administered Orally to Patients With Primary Myelofibrosis (PMF), Post-polycythemia Veramyelofibrosis (PPV-MF) or Post-essentialthrombocythemia-myelofibrosis (PET-MF) and Baseline Platelet Counts ≥50 x109/L and <100 x109/L (EXPAND)
Actual Study Start Date
:
Mar 31, 2011
Actual Primary Completion Date
:
Dec 31, 2019
Actual Study Completion Date
:
Dec 31, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Stratum -1 Participants with baseline Platelet counts of 75-99 x10^9/L |
Drug: Ruxolitinib
Starting dose of ruxolitinib for cohort 1 in dose escalation phase - 5mg twice a day (BID)
Doses will be increased a total of approximately 5mg for successive dosing cohorts based on baseline platelet count
Other Names:
|
| Experimental: Stratum -2 Participants with baseline Platelet counts of 50-74 x10^9/L |
Drug: Ruxolitinib
Starting dose of ruxolitinib for cohort 1 in dose escalation phase - 5mg twice a day (BID)
Doses will be increased a total of approximately 5mg for successive dosing cohorts based on baseline platelet count
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities [28 days]
DLT was defined as the occurrence of any of the following treatment-related toxicities, occurring through Day 28: Any grade ≥ 2 hemorrhagic event ; Any grade thrombocytopenia requiring PLT transfusion; PLT count < 25x109/L*; Grade 4 neutropenia (absolute neutrophil count < 0.5x109/L)*; Grade ≥ 3 febrile neutropenia*; Grade ≥ 2 total serum bilirubin with coincident direct bilirubin ≥ 0.5 mg/dL; Grade 3 non-hematologic toxicity for ≥ 7 consecutive days; Grade 4 non-hematologic toxicity. In the dose escalation stage in the core study period, the starting does in both strata was 5mg bid. Successive cohorts of newly enrolled patients received increasing doses of ruxolitinib until the Maximum Safe Starting Dose (MSSD) was determined. Initially, only patients with PLT counts 75-99 x10^9/L (stratum 1) were allowed to be enrolled. Once safety was established in stratum 1 at the first 2 dose cohorts, eligible population was further expanded to patients with PLT counts 50-74 x10^9/L (stratum 2).
Secondary Outcome Measures
- Number of Treatment Emergent Adverse Events (TEAE's) [approximately 4 years]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
- Number of Subjects Achieving ≥ 50% Reduction in Palpable Spleen Length [24 weeks]
Participants achieving ≥ 50% reduction in palpable spleen length relative to study day 1 by treatment and stratum
- Change in Spleen Length as Measure by Palpation Over Time [Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 168, 252, 336, 420, 504, 588, 672, 756, 1008, 1092]
Defined as measurement of change in spleen length by palpation from baseline
- PK- C Reactive Protein Levels by PK Quartile (AUC0-12) [24 weeks]
To define the PK and C Reactive Protein relationship using PK Quartiles (AUC 0-12, ng*h/mL)
- PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12) [24 weeks]
To define the PK and Interleukin 1 Receptor Antagonist relationship relationship using PK Quartiles (AUC 0-12, ng*h/mL)
- PK- Tissue Necrosis Factor Receptor 2 Levels by PK Quartile (AUC0-12) [24 weeks]
To define the PK and Tissue Necrosis Factor Receptor 2 relationship using PK Quartiles (AUC 0-12, ng*h/mL)
- AUC 0-Inf [0.25 to 0.75, 1 to 3, and 4 to 12 hours postdose on Day 1 and predose, 0.25 to 0.75 hours, and 1 to 3 hours postdose on Day 15, with a random sample on Days 29 and 57]
Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Require treatment for MF and classified at least as intermediate risk level 1 defined by the International Working Group.
-
Platelet count < 100x10 ^9/L at screening or at Study Day 1.
Exclusion Criteria:
- Received platelet transfusion within 14 days prior to Screening evaluations.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Winter Park | Florida | United States | 32789 | |
| 2 | Baltimore | Maryland | United States | 21229 | |
| 3 | Houston | Texas | United States | 77030 | |
| 4 | Vienna | Austria | |||
| 5 | Nanjing | Jiangsu | China | ||
| 6 | Chengdu | Sichuan | China | ||
| 7 | Hangzhou | Zhejiang | China | ||
| 8 | Beijing | China | |||
| 9 | Angers | France | |||
| 10 | Paris | France | |||
| 11 | Pierre-Benite | France | |||
| 12 | Leipzig | Germany | |||
| 13 | Firenze | Italy | |||
| 14 | Milano | Italy | |||
| 15 | Terni | Italy | |||
| 16 | Rotterdam | Netherlands | |||
| 17 | Belfast | United Kingdom | |||
| 18 | London | United Kingdom |
Sponsors and Collaborators
- Incyte Corporation
- Novartis
Investigators
- Study Director: Mark Jones, MD, Incyte Corporation
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01317875
Other Study ID Numbers:
- CINC424A2201
First Posted:
Mar 17, 2011
Last Update Posted:
Mar 9, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted from 03-Mar-2011 to 31-Dec-2019 globally. Participants with MF and baseline PLT of 75 to < 100 × 109/L are enrolled in Stratum 1;and 50 to < 75 × 109/L are enrolled in Stratum 2.. The study has a core period (up to week 24) consisting of 2 phases (dose escalation and safety expansion) followed by an extension period (up to 3 years). Participants received increasing doses of ruxolitinib until the Maximum Safe Starting Dose (MSSD) was determined |
|---|---|
| Pre-assignment Detail | A total of 69 participants enrolled in the study with 44 in Stratum 1 (cohorts 1,2,3,4,5) and 25 in Stratum 2 (Cohorts 1,2,3). |
| Arm/Group Title | Stratum 1 : Cohort 1 | Stratum 1 : Cohort 2 | Stratum 1 : Cohort 3 | Stratum 1 : Cohort 4 | Stratum 1 : Cohort 5 | Stratum 2 : Cohort 1 | Stratum 2 : Cohort 2 | Stratum 2 : Cohort 3 | Stratum 2 : Cohort 4 | Stratum 2 : Cohort 5 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ruxolitinib was administered at 5 mg bid in Participants with baseline Platelet counts of 75-99x10^9/L | Ruxolitinib was administered at 5 mg q.AM / 10 mg q.PM in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered to cohort 3 at 10 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 10 mg q.AM / 15 mg q.PM in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 15 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 5 mg bid in participants with baseline Platelet counts of 50-74x10^9/L | Ruxolitinib was administered at 5 mg q.AM / 10 mg q.PM in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 10 mg bid in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 10 mg q.AM / 15 mg q.PM in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 15 mg bid in participants with baseline Platelet counts of 50-74 x10^9/L |
| Period Title: Overall Study | ||||||||||
| STARTED | 5 | 3 | 20 | 4 | 12 | 3 | 4 | 18 | 0 | 0 |
| COMPLETED | 2 | 1 | 11 | 2 | 3 | 1 | 2 | 3 | 0 | 0 |
| NOT COMPLETED | 3 | 2 | 9 | 2 | 9 | 2 | 2 | 15 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Stratum 1 : Cohort 1 | Stratum 1 : Cohort 2 | Stratum 1 : Cohort 3 | Stratum 1 : Cohort 4 | Stratum 1 : Cohort 5 | Stratum 2 : Cohort 1 | Stratum 2 : Cohort 2 | Stratum 2 : Cohort 3 | Stratum 2 : Cohort 4 | Stratum 2 : Cohort 5 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ruxolitinib was administered at 5 mg bid in Participants with baseline Platelet counts of 75-99x10^9/L | Ruxolitinib was administered at 5 mg q.AM / 10 mg q.PM in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered to cohort 3 at 10 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 10 mg q.AM / 15 mg q.PM) in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 15 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 5 mg bid in participants with baseline Platelet counts of 50-74x10^9/L | Ruxolitinib was administered at 5 mg q.AM / 10 mg q.PM) in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 10 mg bid in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 10 mg q.AM / 15 mg q.PM in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 15 mg bid in participants with baseline Platelet counts of 50-74 x10^9/L | Total of all reporting groups |
| Overall Participants | 5 | 3 | 20 | 4 | 12 | 3 | 4 | 18 | 0 | 0 | 69 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||
| Mean (Standard Deviation) [years] |
63.00
(7.78)
|
54.00
(4.00)
|
63.0
(14.71)
|
70.4
(8.91)
|
75.8
(3.30)
|
67.3
(11.06)
|
72.5
(6.95)
|
68.0
(11.66)
|
66.4
(11.81)
|
||
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
4
80%
|
2
66.7%
|
12
60%
|
2
50%
|
4
33.3%
|
2
66.7%
|
3
75%
|
7
38.9%
|
36
Infinity
|
||
| Male |
1
20%
|
1
33.3%
|
8
40%
|
2
50%
|
8
66.7%
|
1
33.3%
|
1
25%
|
11
61.1%
|
33
Infinity
|
||
| Race/Ethnicity, Customized (Number) [Number] | |||||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
5%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
2
11.1%
|
4
Infinity
|
||
| Not Hispanic or Latino |
4
80%
|
2
66.7%
|
15
75%
|
3
75%
|
7
58.3%
|
2
66.7%
|
0
0%
|
13
72.2%
|
46
Infinity
|
||
| Missing |
1
20%
|
1
33.3%
|
4
20%
|
1
25%
|
5
41.7%
|
1
33.3%
|
3
75%
|
3
16.7%
|
19
Infinity
|
||
| Race/Ethnicity, Customized (Count of Participants) | |||||||||||
| White |
5
100%
|
2
66.7%
|
8
40%
|
4
100%
|
11
91.7%
|
2
66.7%
|
3
75%
|
16
88.9%
|
51
Infinity
|
||
| Asian |
0
0%
|
1
33.3%
|
11
55%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
12
Infinity
|
||
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
1
5.6%
|
2
Infinity
|
||
| Missing |
0
0%
|
0
0%
|
1
5%
|
0
0%
|
0
0%
|
1
33.3%
|
1
25%
|
1
5.6%
|
4
Infinity
|
||
| ECOG Performance Status (Count of Participants) | |||||||||||
| 0 |
1
20%
|
2
66.7%
|
9
45%
|
1
25%
|
6
50%
|
0
0%
|
1
25%
|
4
22.2%
|
24
Infinity
|
||
| 1 |
3
60%
|
1
33.3%
|
9
45%
|
1
25%
|
4
33.3%
|
2
66.7%
|
2
50%
|
10
55.6%
|
32
Infinity
|
||
| 2 |
1
20%
|
0
0%
|
2
10%
|
2
50%
|
2
16.7%
|
1
33.3%
|
1
25%
|
4
22.2%
|
13
Infinity
|
||
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicities |
|---|---|
| Description | DLT was defined as the occurrence of any of the following treatment-related toxicities, occurring through Day 28: Any grade ≥ 2 hemorrhagic event ; Any grade thrombocytopenia requiring PLT transfusion; PLT count < 25x109/L*; Grade 4 neutropenia (absolute neutrophil count < 0.5x109/L)*; Grade ≥ 3 febrile neutropenia*; Grade ≥ 2 total serum bilirubin with coincident direct bilirubin ≥ 0.5 mg/dL; Grade 3 non-hematologic toxicity for ≥ 7 consecutive days; Grade 4 non-hematologic toxicity. In the dose escalation stage in the core study period, the starting does in both strata was 5mg bid. Successive cohorts of newly enrolled patients received increasing doses of ruxolitinib until the Maximum Safe Starting Dose (MSSD) was determined. Initially, only patients with PLT counts 75-99 x10^9/L (stratum 1) were allowed to be enrolled. Once safety was established in stratum 1 at the first 2 dose cohorts, eligible population was further expanded to patients with PLT counts 50-74 x10^9/L (stratum 2). |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Dose Determining Set. Dose was not escalated to enroll participants in Stratum-2 : Cohorts 4 and 5. |
| Arm/Group Title | Stratum 1 : Cohort 1 | Stratum 1 : Cohort 2 | Stratum 1 : Cohort 3 | Stratum 1 : Cohort 4 | Stratum 1 : Cohort 5 | Stratum 2 : Cohort 1 | Stratum 2 : Cohort 2 | Stratum 2 : Cohort 3 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ruxolitinib was administered at 5 mg bid | Ruxolitinib was administered at 5 mg q.AM+ 10 mg q.PM | Ruxolitinib was administered at a starting dose of 10 mg q.AM + 10 mg q.PM | Ruxolitinib was administered at a starting dose of 10 mg q.AM + 15 mg q.PM | Ruxolitinib was administered at a starting dose of 15 mg q.AM + 15 mg q.PM | Ruxolitinib was administered at 5 mg q.AM + 5 mg q.PM | Ruxolitinib was administered at 5 mg q.AM+ 10 mg q.PM | Ruxolitinib was administered at 10 mg q.AM+ 10 mg q.PM |
| Measure Participants | 5 | 3 | 3 | 3 | 12 | 3 | 4 | 12 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.6%
|
| Title | Number of Treatment Emergent Adverse Events (TEAE's) |
|---|---|
| Description | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. |
| Time Frame | approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Population; Multiple dose cohorts within the strata are combined based on the total dose levels as specified in Statistical Analysis Plan |
| Arm/Group Title | Stratum 1 : Group 1 | Stratum 1 : Group 2 | Stratum 1 : Group 3 | Stratum 2 : Group 1 | Stratum 2 : Group 2 |
|---|---|---|---|---|---|
| Arm/Group Description | Ruxolitinib was administered to Cohort 1 (5 mg bid) + Cohort 2 (5 mg q.AM / 10 mg q.PM) in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered to cohort 3 at 10 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered Cohort 4 (10 mg q.AM / 15 mg q.PM) + Cohort 5 (15 mg bid) in Participants with baseline Platelet counts of 75-99 x10^9/L. | Ruxolitinib was administered to Cohort 1 (5 mg bid) + Cohort 2 (5 mg q.AM / 10 mg q.PM) in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered Cohort 3 (10 mg bid) in participants with baseline Platelet counts of 50-74 x10^9/L |
| Measure Participants | 8 | 20 | 16 | 7 | 18 |
| Count of Participants [Participants] |
8
160%
|
20
666.7%
|
16
80%
|
7
175%
|
18
150%
|
| Title | Number of Subjects Achieving ≥ 50% Reduction in Palpable Spleen Length |
|---|---|
| Description | Participants achieving ≥ 50% reduction in palpable spleen length relative to study day 1 by treatment and stratum |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had spleen assessment at week 24. Multiple dose cohorts within the strata are grouped according to total daily dose ranges as specified in Statistical Analysis Plan. |
| Arm/Group Title | Stratum 1 : Group 1 | Stratum 1 : Group 2 | Stratum 1 : Group 3 | Stratum 2 : Group 1 | Stratum 2 : Group 2 |
|---|---|---|---|---|---|
| Arm/Group Description | Ruxolitinib was administered to Cohort 1 (5 mg bid) + Cohort 2 (5 mg q.AM / 10 mg q.PM) in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered to cohort 3 at 10 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered Cohort 4 (10 mg q.AM / 15 mg q.PM) + Cohort 5 (15 mg bid) in Participants with baseline Platelet counts of 75-99 x10^9/L. | Ruxolitinib was administered to Cohort 1 (5 mg bid) + Cohort 2 (5 mg q.AM / 10 mg q.PM) in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered Cohort 3 (10 mg bid) in participants with baseline Platelet counts of 50-74 x10^9/L |
| Measure Participants | 5 | 15 | 13 | 5 | 8 |
| Count of Participants [Participants] |
3
60%
|
6
200%
|
4
20%
|
1
25%
|
3
25%
|
| Title | Change in Spleen Length as Measure by Palpation Over Time |
|---|---|
| Description | Defined as measurement of change in spleen length by palpation from baseline |
| Time Frame | Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 168, 252, 336, 420, 504, 588, 672, 756, 1008, 1092 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Change in spleen length measurement as compared to baseline are summarized by time and by stratum as specified in the SAP. |
| Arm/Group Title | Stratum 1 | Stratum 2 |
|---|---|---|
| Arm/Group Description | Participants with baseline Platelet counts of 75-99 x10^9/L | Participants with baseline Platelet counts of 50-74 x10^9/L |
| Measure Participants | 44 | 25 |
| Day 8 |
-2.8
(2.73)
|
-3.7
(2.98)
|
| Day 15 |
-3.3
(2.7)
|
-5.4
(4.4)
|
| Day 22 |
-5.2
(2.87)
|
-5.4
(4.81)
|
| Day 29 |
-4.4
(3.14)
|
-6.0
(4.23)
|
| Day 43 |
-4.6
(2.74)
|
-5.8
(4.31)
|
| Day 57 |
-4.5
(2.98)
|
-5.6
(4.52)
|
| Day 85 |
-4.5
(3.53)
|
-5.2
(4.32)
|
| Day 113 |
-4.7
(3.29)
|
-6.0
(4.74)
|
| Day 141 |
-4.9
(3.24)
|
-6.7
(4.43)
|
| Day 168 |
-5.2
(3.73)
|
-5.0
(4.78)
|
| Day 252 |
-5.5
(4.40)
|
-3.6
(6.67)
|
| Day 336 |
-5.1
(4.64)
|
-5.3
(4.86)
|
| Day 420 |
-6.1
(4.80)
|
-4.9
(5.75)
|
| Day 504 |
-5.7
(4.0)
|
-4.9
(4.91)
|
| Day 588 |
-4.7
(5.24)
|
-5.4
(5.61)
|
| Day 672 |
-5.8
(5.33)
|
-4.4
(6.60)
|
| Day 756 |
-5.7
(5.22)
|
-6.0
(6.03)
|
| Day 1008 |
-7.6
(3.93)
|
-8.0
(4.55)
|
| Day 1092 |
-6.8
(1.71)
|
-4.2
(5.81)
|
| Title | PK- C Reactive Protein Levels by PK Quartile (AUC0-12) |
|---|---|
| Description | To define the PK and C Reactive Protein relationship using PK Quartiles (AUC 0-12, ng*h/mL) |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Results are summarized by strata, as dose relationship is accounted for by PK quartiles. |
| Arm/Group Title | Stratum 1 | Stratum 2 |
|---|---|---|
| Arm/Group Description | Participants with baseline Platelet counts of 75-99 x10^9/L | Participants with baseline Platelet counts of 50-74 x10^9/L |
| Measure Participants | 44 | 25 |
| Quartile 1 Day 1 |
14
(5.73)
|
12
|
| Quartile 1 Day 29 |
21.2
(31.5)
|
2.6
(2.05)
|
| Quartile 1 Day 168 |
7.6
(8)
|
5.51
(4.98)
|
| Quartile 2 Day 1 |
9.5
(0.707)
|
7.7
|
| Quartile 2 Day 29 |
10.2
(23.8)
|
1.84
(173)
|
| Quartile 2 Day 168 |
8.37
(12.8)
|
2.41
(1.45)
|
| Quartile 3 Day 1 |
6.85
(7.28)
|
6.5
|
| Quartile 3 Day 29 |
2.76
(4.66)
|
7.36
(9.06)
|
| Quartile 3 Day 168 |
7.7
(14.9)
|
4.98
(5.1)
|
| Quartile 4 Day 1 |
0.96
(1.05)
|
5.4
|
| Quartile 4 Day 29 |
1.87
(1.43)
|
12.4
(17.8)
|
| Quartile 4 Day 168 |
4.88
(9.01)
|
4.9
|
| Title | PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12) |
|---|---|
| Description | To define the PK and Interleukin 1 Receptor Antagonist relationship relationship using PK Quartiles (AUC 0-12, ng*h/mL) |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Results are summarized by strata, as dose relationship is accounted for by PK quartiles. |
| Arm/Group Title | Stratum 1 | Stratum 2 |
|---|---|---|
| Arm/Group Description | Participants with baseline Platelet counts of 75-99 x10^9/L | Participants with baseline Platelet counts of 50-74 x10^9/L |
| Measure Participants | 44 | 25 |
| Quartile 1 Day 1 |
188
(116)
|
105
|
| Quartile 1 Day 29 |
267
(334)
|
588
(730)
|
| Quartile 1 Day 168 |
592
(532)
|
379
(419)
|
| Quartile 2 Day 1 |
179
(43.1)
|
133
|
| Quartile 2 Day 29 |
524
(519)
|
600
(649)
|
| Quartile 2 Day 168 |
557
(504)
|
334
(322)
|
| Quartile 3 Day 1 |
319
(288)
|
191
|
| Quartile 3 Day 29 |
304
(327)
|
452
(529)
|
| Quartile 3 Day 168 |
549
(531)
|
960
(792)
|
| Quartile 4 Day 1 |
120
(40.3)
|
148
|
| Quartile 4 Day 29 |
604
(647)
|
475
(464)
|
| Quartile 4 Day 168 |
562
(758)
|
378
|
| Title | PK- Tissue Necrosis Factor Receptor 2 Levels by PK Quartile (AUC0-12) |
|---|---|
| Description | To define the PK and Tissue Necrosis Factor Receptor 2 relationship using PK Quartiles (AUC 0-12, ng*h/mL) |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Results are summarized by strata, as dose relationship is accounted for by PK quartiles. |
| Arm/Group Title | Stratum 1 | Stratum 2 |
|---|---|---|
| Arm/Group Description | Participants with baseline Platelet counts of 75-99 x10^9/L | Participants with baseline Platelet counts of 50-74 x10^9/L |
| Measure Participants | 44 | 25 |
| Quartile 1 Day 1 |
24
(19.8)
|
6.2
|
| Quartile 1 Day 29 |
20.5
(19.7)
|
25.7
(14.4)
|
| Quartile 1 Day 168 |
14
(4.24)
|
22.6
(12.6)
|
| Quartile 2 Day 1 |
13.5
(0.707)
|
8.2
|
| Quartile 2 Day 29 |
14.9
(6.62)
|
12.3
(7.67)
|
| Quartile 2 Day 168 |
36.1
(22.9)
|
18.4
(12.6)
|
| Quartile 3 Day 1 |
21
(9.9)
|
47
|
| Quartile 3 Day 29 |
12.9
(4.32)
|
13.7
(11.6)
|
| Quartile 3 Day 168 |
13.3
(5.8)
|
12.4
(7.99)
|
| Quartile 4 Day 1 |
15
(4.24)
|
24
|
| Quartile 4 Day 29 |
15.7
(9.13)
|
24.6
(17.4)
|
| Quartile 4 Day 168 |
14.3
(7.67)
|
11
|
| Title | AUC 0-Inf |
|---|---|
| Description | Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity |
| Time Frame | 0.25 to 0.75, 1 to 3, and 4 to 12 hours postdose on Day 1 and predose, 0.25 to 0.75 hours, and 1 to 3 hours postdose on Day 15, with a random sample on Days 29 and 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Results are summarized by strata; dose relationship is accounted for by PK quartile grouping. |
| Arm/Group Title | 5mg BID | 10mg BID | 15 mg BID |
|---|---|---|---|
| Arm/Group Description | ruxolitinib was administered at 5 mg BID | ruxolitinib was administered at 10 mg BID | ruxolitinib was administered at 15 mg BID |
| Measure Participants | 15 | 16 | 9 |
| Mean (Standard Deviation) [nM*hr] |
1027
(357)
|
1930
(562)
|
3756
(916)
|
Adverse Events
| Time Frame | Up to 4 years | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AE additional description | |||||||||||||||||||
| Arm/Group Title | Stratum 1 : Cohort 1 | Stratum 1 : Cohort 2 | Stratum 1 : Cohort 3 | Stratum 1 : Cohort 4 | Stratum 1 : Cohort 5 | Stratum 2 : Cohort 1 | Stratum 2 : Cohort 2 | Stratum 2 : Cohort 3 | Stratum 2 : Cohort 4 | Stratum 2 : Cohort 5 | ||||||||||
| Arm/Group Description | Ruxolitinib was administered at 5 mg bid in Participants with baseline Platelet counts of 75-99x10^9/L | Ruxolitinib was administered at 5 mg q.AM / 10 mg q.PM in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered to cohort 3 at 10 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 10 mg q.AM / 15 mg q.PM) in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 15 mg bid in Participants with baseline Platelet counts of 75-99 x10^9/L | Ruxolitinib was administered at 5 mg bid in participants with baseline Platelet counts of 50-74x10^9/L | Ruxolitinib was administered at 5 mg q.AM / 10 mg q.PM) in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 10 mg bid in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 10 mg q.AM / 15 mg q.PM in participants with baseline Platelet counts of 50-74 x10^9/L | Ruxolitinib was administered at 15 mg bid in participants with baseline Platelet counts of 50-74 x10^9/L | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| Stratum 1 : Cohort 1 | Stratum 1 : Cohort 2 | Stratum 1 : Cohort 3 | Stratum 1 : Cohort 4 | Stratum 1 : Cohort 5 | Stratum 2 : Cohort 1 | Stratum 2 : Cohort 2 | Stratum 2 : Cohort 3 | Stratum 2 : Cohort 4 | Stratum 2 : Cohort 5 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/3 (0%) | 3/20 (15%) | 1/4 (25%) | 0/12 (0%) | 1/3 (33.3%) | 0/4 (0%) | 4/18 (22.2%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| Stratum 1 : Cohort 1 | Stratum 1 : Cohort 2 | Stratum 1 : Cohort 3 | Stratum 1 : Cohort 4 | Stratum 1 : Cohort 5 | Stratum 2 : Cohort 1 | Stratum 2 : Cohort 2 | Stratum 2 : Cohort 3 | Stratum 2 : Cohort 4 | Stratum 2 : Cohort 5 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/5 (40%) | 2/3 (66.7%) | 10/20 (50%) | 4/4 (100%) | 5/12 (41.7%) | 3/3 (100%) | 3/4 (75%) | 9/18 (50%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anaemia | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Leukocytosis | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Splenomegaly | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Thrombocytopenia | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Leukopenia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Cardiac arrest | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Sinus node dysfunction | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Atrial fibrillation | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Cardiac failure | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Right ventricular failure | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal pain | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Anal haemorrhage | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Diarrhoea | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastrointestinal haemorrhage | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Ascites | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastric ulcer | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Intestinal obstruction | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Large intestinal obstruction | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| General disorders | ||||||||||||||||||||
| Asthenia | 1/5 (20%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Drug withdrawal syndrome | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Fatigue | 1/5 (20%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| General physical health deterioration | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Oedema peripheral | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pyrexia | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Sudden death | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Multiple organ dysfunction syndrome | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||
| Cholelithiasis | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gallbladder obstruction | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Appendicitis | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Meningitis viral | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pneumonia | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pneumonia viral | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Staphylococcal sepsis | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Bronchitis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Disseminated tuberculosis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Influenza | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Sepsis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Fall | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Multiple fractures | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Subdural haematoma | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Wound haemorrhage | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Splenic rupture | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Thoracic vertebral fracture | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Investigations | ||||||||||||||||||||
| Blood bilirubin increased | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Diabetes mellitus | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Back pain | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Haemarthrosis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Acute myeloid leukaemia | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Basal cell carcinoma | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Chloroma | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Myelofibrosis | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Bronchial carcinoma | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Chronic myeloid leukaemia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Laryngeal cancer | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Transformation to acute myeloid leukaemia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Haemorrhage intracranial | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| IIIrd nerve paralysis | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Neuralgia | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Syncope | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Presyncope | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Acute kidney injury | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Calculus bladder | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Dyspnoea | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pulmonary embolism | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 2/12 (16.7%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Respiratory failure | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Lung disorder | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pleural effusion | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pulmonary hypertension | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Bleeding varicose vein | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Deep vein thrombosis | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Haematoma | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Peripheral artery occlusion | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| Stratum 1 : Cohort 1 | Stratum 1 : Cohort 2 | Stratum 1 : Cohort 3 | Stratum 1 : Cohort 4 | Stratum 1 : Cohort 5 | Stratum 2 : Cohort 1 | Stratum 2 : Cohort 2 | Stratum 2 : Cohort 3 | Stratum 2 : Cohort 4 | Stratum 2 : Cohort 5 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 3/3 (100%) | 20/20 (100%) | 4/4 (100%) | 12/12 (100%) | 3/3 (100%) | 4/4 (100%) | 18/18 (100%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anaemia | 3/5 (60%) | 2/3 (66.7%) | 11/20 (55%) | 2/4 (50%) | 6/12 (50%) | 1/3 (33.3%) | 3/4 (75%) | 8/18 (44.4%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Haemorrhagic diathesis | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Iron deficiency anaemia | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Leukopenia | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Neutropenia | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Splenomegaly | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Thrombocytopenia | 4/5 (80%) | 2/3 (66.7%) | 9/20 (45%) | 3/4 (75%) | 11/12 (91.7%) | 1/3 (33.3%) | 4/4 (100%) | 14/18 (77.8%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Leukocytosis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 3/18 (16.7%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Lymphadenopathy | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Platelet aggregation inhibition | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Atrial fibrillation | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pericardial effusion | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Tachycardia | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Ventricular tachycardia | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Diastolic dysfunction | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Extrasystoles | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Sinus bradycardia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Tricuspid valve disease | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||
| Deafness unilateral | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Hypoacusis | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Tinnitus | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Vertigo | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Eye disorders | ||||||||||||||||||||
| Cataract | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Conjunctival haemorrhage | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Dry eye | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Uveitis | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Eye haemorrhage | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Vision blurred | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal distension | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 2/18 (11.1%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Abdominal pain | 0/5 (0%) | 1/3 (33.3%) | 5/20 (25%) | 0/4 (0%) | 2/12 (16.7%) | 1/3 (33.3%) | 0/4 (0%) | 4/18 (22.2%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Abdominal pain upper | 1/5 (20%) | 1/3 (33.3%) | 2/20 (10%) | 1/4 (25%) | 2/12 (16.7%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Constipation | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 2/4 (50%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Diarrhoea | 2/5 (40%) | 1/3 (33.3%) | 6/20 (30%) | 2/4 (50%) | 3/12 (25%) | 1/3 (33.3%) | 2/4 (50%) | 5/18 (27.8%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Dyspepsia | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Enteritis | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastritis | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastrointestinal disorder | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gingival pain | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Haemorrhoids | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Intestinal dilatation | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Melaena | 0/5 (0%) | 1/3 (33.3%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Nausea | 1/5 (20%) | 1/3 (33.3%) | 1/20 (5%) | 1/4 (25%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 4/18 (22.2%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Oesophagitis | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Rectal haemorrhage | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 2/12 (16.7%) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Toothache | 1/5 (20%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Vomiting | 1/5 (20%) | 1/3 (33.3%) | 3/20 (15%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 3/18 (16.7%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Abdominal discomfort | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Aphthous ulcer | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Dental caries | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Dieulafoy's vascular malformation | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastrooesophageal reflux disease | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Mouth ulceration | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Oral disorder | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Oral mucosal blistering | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Stomatitis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| General disorders | ||||||||||||||||||||
| Asthenia | 2/5 (40%) | 0/3 (0%) | 3/20 (15%) | 0/4 (0%) | 2/12 (16.7%) | 2/3 (66.7%) | 0/4 (0%) | 5/18 (27.8%) | 5/0 (Infinity) | 5/0 (Infinity) | ||||||||||
| Chest pain | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Fatigue | 0/5 (0%) | 0/3 (0%) | 3/20 (15%) | 1/4 (25%) | 3/12 (25%) | 0/3 (0%) | 1/4 (25%) | 3/18 (16.7%) | 3/0 (Infinity) | 3/0 (Infinity) | ||||||||||
| Feeling cold | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Hernia pain | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Influenza like illness | 1/5 (20%) | 1/3 (33.3%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Oedema peripheral | 0/5 (0%) | 1/3 (33.3%) | 1/20 (5%) | 2/4 (50%) | 1/12 (8.3%) | 1/3 (33.3%) | 1/4 (25%) | 3/18 (16.7%) | 3/0 (Infinity) | 3/0 (Infinity) | ||||||||||
| Pain | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Pyrexia | 1/5 (20%) | 0/3 (0%) | 6/20 (30%) | 0/4 (0%) | 2/12 (16.7%) | 2/3 (66.7%) | 1/4 (25%) | 4/18 (22.2%) | 4/0 (Infinity) | 4/0 (Infinity) | ||||||||||
| Swelling face | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Chills | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Malaise | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Mucosal inflammation | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Oedema | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Xerosis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||
| Hepatic failure | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Hypertransaminasaemia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Jaundice | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Bronchitis | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 1/3 (33.3%) | 2/4 (50%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Bronchitis viral | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Conjunctivitis | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastroenteritis viral | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gastrointestinal infection | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Genital herpes | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Herpes virus infection | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Infection | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Nasopharyngitis | 0/5 (0%) | 1/3 (33.3%) | 4/20 (20%) | 1/4 (25%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 5/18 (27.8%) | 5/0 (Infinity) | 5/0 (Infinity) | ||||||||||
| Oral herpes | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 2/12 (16.7%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Oral infection | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Respiratory tract infection | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Rhinitis | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Tooth infection | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Upper respiratory tract infection | 0/5 (0%) | 1/3 (33.3%) | 3/20 (15%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Urinary tract infection | 1/5 (20%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Varicella zoster virus infection | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Campylobacter infection | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Cystitis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Escherichia urinary tract infection | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Folliculitis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Herpes simplex | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Herpes zoster | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Influenza | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Oropharyngeal candidiasis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Periodontitis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Pharyngitis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pharyngotonsillitis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Pneumonia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Vulvovaginal candidiasis | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Accident | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Ankle fracture | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Contusion | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 2/4 (50%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Fall | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Lower limb fracture | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Procedural pain | 2/5 (40%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Subdural haematoma | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Anaemia postoperative | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Head injury | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Ligament sprain | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Scratch | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Spinal fracture | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Thoracic vertebral fracture | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Tooth fracture | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Wound | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Investigations | ||||||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Alanine aminotransferase increased | 0/5 (0%) | 0/3 (0%) | 3/20 (15%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Aspartate aminotransferase increased | 0/5 (0%) | 0/3 (0%) | 3/20 (15%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Blood alkaline phosphatase increased | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Blood bilirubin increased | 0/5 (0%) | 1/3 (33.3%) | 4/20 (20%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Blood creatinine increased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 2/12 (16.7%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Blood fibrinogen decreased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Blood uric acid increased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Coagulation factor V level decreased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Coagulation factor VII level decreased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Coagulation factor X level decreased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Gamma-glutamyltransferase increased | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Haemoglobin decreased | 0/5 (0%) | 0/3 (0%) | 4/20 (20%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Lymphocyte count decreased | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Mean cell volume increased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Neutrophil count decreased | 0/5 (0%) | 0/3 (0%) | 3/20 (15%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Platelet count decreased | 0/5 (0%) | 1/3 (33.3%) | 6/20 (30%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Prothrombin level decreased | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Prothrombin time shortened | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Red blood cell count decreased | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Weight increased | 0/5 (0%) | 1/3 (33.3%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| White blood cell count decreased | 0/5 (0%) | 0/3 (0%) | 5/20 (25%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Amylase increased | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Blood calcium decreased | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Blood lactate dehydrogenase increased | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Blood urea increased | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Cardiac murmur | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Lipase increased | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Urine output increased | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| White blood cell count increased | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Decreased appetite | 1/5 (20%) | 0/3 (0%) | 1/20 (5%) | 1/4 (25%) | 0/12 (0%) | 1/3 (33.3%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Hyperglycaemia | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Hyperuricaemia | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 1/12 (8.3%) | 2/3 (66.7%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Hypocalcaemia | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 5/18 (27.8%) | 5/0 (Infinity) | 5/0 (Infinity) | ||||||||||
| Hyponatraemia | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Diabetes mellitus | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Gout | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Hyperkalaemia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Hypertriglyceridaemia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Hypokalaemia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Iron overload | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Arthralgia | 1/5 (20%) | 1/3 (33.3%) | 2/20 (10%) | 1/4 (25%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Back pain | 0/5 (0%) | 1/3 (33.3%) | 4/20 (20%) | 0/4 (0%) | 0/12 (0%) | 2/3 (66.7%) | 1/4 (25%) | 3/18 (16.7%) | 3/0 (Infinity) | 3/0 (Infinity) | ||||||||||
| Muscle spasms | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 2/12 (16.7%) | 1/3 (33.3%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Muscular weakness | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Musculoskeletal chest pain | 1/5 (20%) | 1/3 (33.3%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Musculoskeletal pain | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Neck pain | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pain in extremity | 1/5 (20%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 3/12 (25%) | 0/3 (0%) | 3/4 (75%) | 3/18 (16.7%) | 3/0 (Infinity) | 3/0 (Infinity) | ||||||||||
| Bone pain | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Musculoskeletal stiffness | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Myalgia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Pain in jaw | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Basal cell carcinoma | 1/5 (20%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Burning sensation | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 1/4 (25%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Dizziness | 2/5 (40%) | 0/3 (0%) | 2/20 (10%) | 1/4 (25%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Haemorrhage intracranial | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Headache | 2/5 (40%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 3/12 (25%) | 1/3 (33.3%) | 1/4 (25%) | 4/18 (22.2%) | 4/0 (Infinity) | 4/0 (Infinity) | ||||||||||
| Hypoaesthesia | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Paraesthesia | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Polyneuropathy | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Memory impairment | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Presyncope | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Somnolence | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Tremor | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Psychiatric disorders | ||||||||||||||||||||
| Insomnia | 3/5 (60%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 1/3 (33.3%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Nervousness | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Depression | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Azotaemia | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Bladder pain | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Chronic kidney disease | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Micturition urgency | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Pollakiuria | 1/5 (20%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Renal pain | 1/5 (20%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Dysuria | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Haematuria | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Renal failure | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||
| Erectile dysfunction | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Chronic obstructive pulmonary disease | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Cough | 0/5 (0%) | 1/3 (33.3%) | 2/20 (10%) | 0/4 (0%) | 3/12 (25%) | 2/3 (66.7%) | 2/4 (50%) | 6/18 (33.3%) | 6/0 (Infinity) | 6/0 (Infinity) | ||||||||||
| Dyspnoea | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Dyspnoea exertional | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 1/4 (25%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Epistaxis | 2/5 (40%) | 0/3 (0%) | 5/20 (25%) | 1/4 (25%) | 2/12 (16.7%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Oropharyngeal pain | 1/5 (20%) | 1/3 (33.3%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 1/3 (33.3%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Rhinorrhoea | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Wheezing | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Dysphonia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Pleural effusion | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Productive cough | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Rales | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Ecchymosis | 0/5 (0%) | 2/3 (66.7%) | 6/20 (30%) | 0/4 (0%) | 0/12 (0%) | 1/3 (33.3%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Night sweats | 0/5 (0%) | 0/3 (0%) | 2/20 (10%) | 0/4 (0%) | 0/12 (0%) | 1/3 (33.3%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Petechiae | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Pruritus | 0/5 (0%) | 0/3 (0%) | 3/20 (15%) | 0/4 (0%) | 0/12 (0%) | 1/3 (33.3%) | 2/4 (50%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Purpura | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 0/12 (0%) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Rash maculo-papular | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Skin lesion | 0/5 (0%) | 1/3 (33.3%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Acne | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Pain of skin | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Rash | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Skin discolouration | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Haematoma | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 1/4 (25%) | 1/12 (8.3%) | 0/3 (0%) | 0/4 (0%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Hypertension | 0/5 (0%) | 0/3 (0%) | 1/20 (5%) | 0/4 (0%) | 1/12 (8.3%) | 1/3 (33.3%) | 0/4 (0%) | 4/18 (22.2%) | 4/0 (Infinity) | 4/0 (Infinity) | ||||||||||
| Lymphoedema | 0/5 (0%) | 0/3 (0%) | 0/20 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Haemorrhage | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Hot flush | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
| Pallor | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 2/18 (11.1%) | 2/0 (Infinity) | 2/0 (Infinity) | ||||||||||
| Peripheral ischaemia | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 1/4 (25%) | 0/18 (0%) | 0/0 (NaN) | 0/0 (NaN) | ||||||||||
| Systolic hypertension | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/3 (0%) | 0/4 (0%) | 1/18 (5.6%) | 1/0 (Infinity) | 1/0 (Infinity) | ||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Clinical Study Agreement
Results Point of Contact
| Name/Title | Incyte Corporation Call Center, Study Director |
|---|---|
| Organization | Incyte Corporation |
| Phone | 1-855-463-3463 |
| medinfo@incyte.com |
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01317875
Other Study ID Numbers:
- CINC424A2201
First Posted:
Mar 17, 2011
Last Update Posted:
Mar 9, 2022
Last Verified:
Jan 1, 2022