Safety Study of PLX108-01 in Patients With Solid Tumors
Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01004861
Collaborator
Plexxikon (Industry)
132
13
1
108.8
10.2
0.1
Study Details
Study Description
Brief Summary
PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity. The primary objective of this study is to evaluate the safety and pharmacokinetics of orally administered PLX3397 in patients with advanced, incurable, solid tumors in which these target kinases are linked to disease pathophysiology. The secondary objective is to measure the pharmacodynamic activity of PLX3397 via blood, plasma and urine biomarkers of Fms activity.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
132 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX3397 in Patients With Advanced, Incurable, Solid Tumors in Which the Target Kinases Are Linked to Disease Pathophysiology
Actual Study Start Date
:
Oct 1, 2009
Actual Primary Completion Date
:
Jan 31, 2018
Actual Study Completion Date
:
Oct 25, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PLX3397
|
Drug: PLX3397
Capsules administered once or twice daily, continuous dosing
|
Outcome Measures
Primary Outcome Measures
- Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population) [Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose)]
Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension (Efficacy Evaluable Population) [Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose)]
Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Duration of Response (Efficacy Evaluable Population) - Dose Extension [From initial response until disease progression or death, up to approximately 30 months postdose]
Duration of Response (DOR) is defined as the number of days from the date of initial response (CR or PR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, DOR is censored as of the date of their last imaging exam of target or non-target lesions prior to post-surgery and/or off-treatment scans.
- Progression-free Survival (Efficacy Evaluable Population) - Dose Extension [From Cycle 1 Day 1 to disease progression or death]
Progression-Free Survival (PFS) is defined as the number of days from the first day of treatment to the first documented disease progression or date of death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, PFS is censored at the date of last evaluable tumor assessment.
- Best Overall Tumor Response (PVNS Cohort) Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension [Every 2 months beginning Cycle 3, Day 1 until disease progression]
Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Cmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation [Cycle 1, Day 15]
Cycle 1 Day 15 pharmacokinetic (PK) timepoints taken are: For once daily (QD) dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For twice a day (BID) dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned.
- Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Tmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation [Cycle 1, Day 15]
Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned.
- Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Area Under the Curve (AUC0-24), Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation [Cycle 1, Day 15 (QD dosing: predose [morning] and 0.5, 1, 2, 4, and 8 hours postdose; BID dosing: predose [morning] and 1, 2, 4, and 7 hours postdose)]
Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing, predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned.
- Numeric Rating Scale (NRS) for PVNS Symptoms Sum of Scores Through Cycle 2 (Efficacy Evaluable Population) - Dose Extension [Baseline, Cycle 1 Day 15, Cycle 2, Cycle 3, Cycle 12, Cycle 24, Cycle 36, and Cycle 46 (each cycle was 28 days)]
The NRS for PVNS Symptoms instrument is a 5-item self-administered questionnaire to assess the "worst" of each of the symptoms pain, swelling, stiffness, instability and limited motion in the last 24 hours. A 0 to 10 NRS is provided for each symptom. For pain, 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine". For the other 4 symptoms, 0 indicates "no (symptom)" and 10 indicates "(symptom) worst imaginable", e.g., "swelling - worst imaginable." Higher scores indicated worse outcome.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age 18 and older
-
Solid tumors refractory to standard therapy
-
For the Extension cohorts, patients must have measurable disease by RECIST criteria and meet the following disease-specific criteria:
-
For advanced or recurrent mucoepidermal carcinoma (MEC) of the salivary gland, patients must not be candidates for curative surgery or radiotherapy.
-
For pigmented villo-nodular synovitis (PVNS), patients must have a histologically confirmed diagnosis of inoperable progressive or relapsing PVNS, or resectable tumor requesting mutilating surgery, as well as demonstrated progressive disease in the last 12 months.
-
For gastrointestinal stromal tumors (GIST), patients must have failed previous therapy with imatinib and sunitinib. Patients with known PDGFR mutations are excluded, but mutation testing is not required for study entry.
-
For anaplastic thyroid cancer (ATC), patients must have histologically or cytologically diagnosed advanced ATC.
-
For metastatic solid tumors with documented malignant pleural and/or peritoneal effusions, patients must not be receiving specific therapy for the effusion or have an indwelling drain.
-
Eastern Cooperative Oncology Group performance status 0 or 1
-
Life expectancy >= 3 months
-
Adequate hepatic, renal, and bone marrow function
Exclusion Criteria:
-
Specific anti-cancer therapy within 3 weeks of study start
-
Uncontrolled intercurrent illness
-
Refractory nausea or vomiting, or malabsorption
-
Mean corrected QT interval (QTc) >= 450 msec (for males) or QTc >= 470 msec (for females)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | HonorHealth | Scottsdale | Arizona | United States | 85258 |
| 2 | UCLA | Los Angeles | California | United States | 90404 |
| 3 | Rocky Mountain Cancer Centers | Denver | Colorado | United States | 80218 |
| 4 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 5 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 6 | Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada | United States | 89169 |
| 7 | Memorial Sloan-Kettering Cancer Center (MSKCC) | New York | New York | United States | 10065 |
| 8 | Pennsylvania Oncology Hematology Associates | Philadelphia | Pennsylvania | United States | 19106 |
| 9 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 10 | Vanderbilt-Ingram Medical Center | Nashville | Tennessee | United States | 37232 |
| 11 | Texas Oncology, PA (North) | Dallas | Texas | United States | 75246 |
| 12 | Virginia Oncology Associates | Norfolk | Virginia | United States | 23502 |
| 13 | Evergreen Hematology & Oncology | Spokane | Washington | United States | 99218 |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
- Plexxikon
Investigators
- Study Director: Medical Director, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier:
NCT01004861
Other Study ID Numbers:
- PLX108-01
First Posted:
Oct 30, 2009
Last Update Posted:
Jan 4, 2022
Last Verified:
Dec 1, 2021
Study Results
Participant Flow
| Recruitment Details | The dose escalation phase administered ascending daily oral doses of PLX3397 to patients with solid tumors and evaluated PK and toxicity. Once the recommended phase 2 dose was reached, 6 extension cohorts were enrolled, consisting of a variety of tumor types. |
|---|---|
| Pre-assignment Detail | At least 3 participants and up to 6 participants were to be enrolled in each dose level using 100% dose increments for each level in the absence of Grade 2 or greater drug-attributable toxicity. Dose escalation was only permitted if adequate safety and tolerability were observed at the previous lower dose for 28 days for the first 3 participants. |
| Arm/Group Title | Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | Dose Extension: MEC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Dose Extension: PVNS Cohort PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM) | Dose Extension: GIST Cohort 1000 mg/Day (600mg AM, 400mg PM) | Dose Extension: ATC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Dose Extension: Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM) | Dose Extension: Other Tumors 1000 mg/Day (600mg AM, 400mg PM) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. | Participants with advanced or recurrent mucoepidermoid carcinoma (MEC) who received PLX3397. | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. | Participants with advanced gastrointestinal stromal tumor (GIST) who received PLX3397. | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. | Participants with advanced solid tumors with malignant effusion who received PLX3397. | Participants with other solid tumor types who received PLX3397. |
| Period Title: Overall Study | |||||||||||||
| STARTED | 3 | 6 | 6 | 6 | 7 | 6 | 7 | 4 | 39 | 11 | 9 | 8 | 20 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 6 | 6 | 6 | 7 | 6 | 7 | 4 | 39 | 11 | 9 | 8 | 20 |
Baseline Characteristics
| Arm/Group Title | Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day | Dose Escalation Cohort 6: 1200 mg/Day | Dose Escalation Cohort 7: 1000 mg/Day | Dose Extension: MEC Cohort | Dose Extension: PVNS Cohort | Dose Extension: GIST Cohort | Dose Extension: ATC Cohort | Dose Extension: Malignant Effusion Cohort | Dose Extension: Other Solid Tumor Type Cohort | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. | Participants with advanced mucoepidermoid carcinoma (MEC) who received PLX3397. | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. | Participants with advanced gastrointestinal stromal tumor (GIS) who received PLX3397. | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. | Participants with advanced solid tumors with malignant effusion who received PLX3397. | Participants with other solid tumor types who received PLX3397. | Total of all reporting groups |
| Overall Participants | 3 | 6 | 6 | 6 | 7 | 6 | 7 | 4 | 39 | 11 | 9 | 8 | 20 | 132 |
| Age (Count of Participants) | ||||||||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
66.7%
|
2
33.3%
|
2
33.3%
|
3
50%
|
5
71.4%
|
3
50%
|
5
71.4%
|
4
100%
|
37
94.9%
|
8
72.7%
|
3
33.3%
|
4
50%
|
15
75%
|
93
70.5%
|
| >=65 years |
1
33.3%
|
4
66.7%
|
4
66.7%
|
3
50%
|
2
28.6%
|
3
50%
|
2
28.6%
|
0
0%
|
2
5.1%
|
3
27.3%
|
6
66.7%
|
4
50%
|
5
25%
|
39
29.5%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||||||||||
| Mean (Standard Deviation) [years] |
62.7
(10.1)
|
65.7
(2.3)
|
63.5
(8.6)
|
61.5
(19.1)
|
52.3
(15.0)
|
56.3
(17.1)
|
50.4
(19.8)
|
47.3
(18.4)
|
45.1
(14.0)
|
57.6
(12.1)
|
65.9
(14.7)
|
58.1
(13.3)
|
52.0
(15.1)
|
58.3
(14.9)
|
| Sex: Female, Male (Count of Participants) | ||||||||||||||
| Female |
2
66.7%
|
4
66.7%
|
3
50%
|
3
50%
|
4
57.1%
|
3
50%
|
6
85.7%
|
1
25%
|
22
56.4%
|
6
54.5%
|
4
44.4%
|
5
62.5%
|
5
25%
|
68
51.5%
|
| Male |
1
33.3%
|
2
33.3%
|
3
50%
|
3
50%
|
3
42.9%
|
3
50%
|
1
14.3%
|
3
75%
|
17
43.6%
|
5
45.5%
|
5
55.6%
|
3
37.5%
|
15
75%
|
64
48.5%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||||||
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
3
7.7%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
5
3.8%
|
| White |
3
100%
|
6
100%
|
6
100%
|
6
100%
|
7
100%
|
5
83.3%
|
7
100%
|
4
100%
|
33
84.6%
|
10
90.9%
|
8
88.9%
|
8
100%
|
18
90%
|
121
91.7%
|
| Black of African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
7.7%
|
0
0%
|
0
0%
|
0
0%
|
1
5%
|
4
3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5%
|
1
0.8%
|
| Multiple races |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
1
0.8%
|
| Region of Enrollment (participants) [Number] | ||||||||||||||
| United States |
3
100%
|
6
100%
|
6
100%
|
6
100%
|
7
100%
|
6
100%
|
7
100%
|
4
100%
|
39
100%
|
11
100%
|
9
100%
|
8
100%
|
20
100%
|
41
31.1%
|
Outcome Measures
| Title | Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population) |
|---|---|
| Description | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Time Frame | Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Best overall tumor response was assessed in the Efficacy Evaluable Population. |
| Arm/Group Title | Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | All Participants |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. | All participants with advanced, incurable, solid tumors who received PL3397. |
| Measure Participants | 3 | 5 | 5 | 5 | 6 | 5 | 6 | 35 |
| Censored participants |
0
0%
|
1
16.7%
|
2
33.3%
|
0
0%
|
3
42.9%
|
0
0%
|
3
42.9%
|
9
225%
|
| CR |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| PR |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
1
25%
|
| SD |
0
0%
|
1
16.7%
|
0
0%
|
2
33.3%
|
3
42.9%
|
1
16.7%
|
1
14.3%
|
8
200%
|
| PD |
3
100%
|
4
66.7%
|
3
50%
|
3
50%
|
2
28.6%
|
4
66.7%
|
3
42.9%
|
22
550%
|
| NE |
0
0%
|
0
0%
|
2
33.3%
|
0
0%
|
1
14.3%
|
0
0%
|
1
14.3%
|
4
100%
|
| Title | Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension (Efficacy Evaluable Population) |
|---|---|
| Description | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Time Frame | Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Best overall tumor response was assessed in the Efficacy Evaluable Population. |
| Arm/Group Title | Dose Extension: MEC Cohort | Dose Extension: PVNS Cohort | Dose Extension: GIST Cohort | Dose Extension: ATC Cohort | Dose Extension: Malignant Effusion Cohort | Dose Extension: Other Solid Tumor Type Cohort |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced mucoepidermoid carcinoma (MEC) who received PLX3397. | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. | Participants with advanced gastrointestinal stromal tumor (GIST) who received PLX3397. | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. | Participants with advanced solid tumors with malignant effusion who received PLX3397. | Participants with other solid tumor types who received PLX3397. |
| Measure Participants | 2 | 37 | 9 | 6 | 6 | 14 |
| CR |
0
0%
|
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| PR |
0
0%
|
22
366.7%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| SD |
1
33.3%
|
8
133.3%
|
4
66.7%
|
0
0%
|
3
42.9%
|
7
116.7%
|
| PD |
1
33.3%
|
1
16.7%
|
5
83.3%
|
6
100%
|
2
28.6%
|
6
100%
|
| NE |
0
0%
|
4
66.7%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
| Overall response rate (CR or PR) |
0
0%
|
24
400%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| Title | Duration of Response (Efficacy Evaluable Population) - Dose Extension |
|---|---|
| Description | Duration of Response (DOR) is defined as the number of days from the date of initial response (CR or PR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, DOR is censored as of the date of their last imaging exam of target or non-target lesions prior to post-surgery and/or off-treatment scans. |
| Time Frame | From initial response until disease progression or death, up to approximately 30 months postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of response was assessed among participants with response of CR or PR in the Efficacy Evaluable Population. |
| Arm/Group Title | Dose Extension: MEC Cohort | Dose Extension: PVNS Cohort | Dose Extension: GIST Cohort | Dose Extension: ATC Cohort | Dose Extension: Malignant Effusion Cohort | Dose Extension: Other Solid Tumor Type Cohort |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced mucoepidermoid carcinoma (MEC) who received PLX3397. | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. | Participants with advanced gastrointestinal stromal tumor (GIS) who received PLX3397. | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. | Participants with advanced solid tumors with malignant effusion who received PLX3397. | Participants with other solid tumor types who received PLX3397. |
| Measure Participants | 0 | 24 | 0 | 0 | 0 | 1 |
| Median (95% Confidence Interval) [days] |
NA
|
115
|
| Title | Progression-free Survival (Efficacy Evaluable Population) - Dose Extension |
|---|---|
| Description | Progression-Free Survival (PFS) is defined as the number of days from the first day of treatment to the first documented disease progression or date of death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, PFS is censored at the date of last evaluable tumor assessment. |
| Time Frame | From Cycle 1 Day 1 to disease progression or death |
Outcome Measure Data
| Analysis Population Description |
|---|
| Progression-free survival was assessed in the Efficacy Evaluable Population. |
| Arm/Group Title | Dose Extension: MEC Cohort | Dose Extension: PVNS Cohort | Dose Extension: GIST Cohort | Dose Extension: ATC Cohort | Dose Extension: Malignant Effusion Cohort | Dose Extension: Other Solid Tumor Type Cohort |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced mucoepidermoid carcinoma (MEC) who received PLX3397. | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. | Participants with advanced gastrointestinal stromal tumor (GIST) who received PLX3397. | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. | Participants with advanced solid tumors with malignant effusion who received PLX3397. | Participants with other solid tumor types who received PLX3397. |
| Measure Participants | 2 | 37 | 9 | 6 | 6 | 14 |
| Median (95% Confidence Interval) [days] |
NA
|
NA
|
54
|
50
|
78
|
161
|
| Title | Best Overall Tumor Response (PVNS Cohort) Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension |
|---|---|
| Description | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Time Frame | Every 2 months beginning Cycle 3, Day 1 until disease progression |
Outcome Measure Data
| Analysis Population Description |
|---|
| Best overall tumor response was assessed in the Efficacy Evaluable Population. |
| Arm/Group Title | PVNS Cohort |
|---|---|
| Arm/Group Description | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. |
| Measure Participants | 37 |
| CR |
2
66.7%
|
| PR |
22
733.3%
|
| SD |
8
266.7%
|
| PD |
1
33.3%
|
| NE |
4
133.3%
|
| Overall response rate (CR or PR) |
24
800%
|
| Title | Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Cmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation |
|---|---|
| Description | Cycle 1 Day 15 pharmacokinetic (PK) timepoints taken are: For once daily (QD) dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For twice a day (BID) dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. |
| Time Frame | Cycle 1, Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. |
| Measure Participants | 3 | 5 | 5 | 5 | 6 | 5 | 6 |
| Median (Full Range) [ng/mL] |
1730
|
3630
|
3160
|
6570
|
6290
|
10600
|
6320
|
| Title | Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Tmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation |
|---|---|
| Description | Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. |
| Time Frame | Cycle 1, Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. |
| Measure Participants | 3 | 5 | 5 | 5 | 6 | 5 | 6 |
| Median (Full Range) [hour] |
2.00
|
1.97
|
0.98
|
1.04
|
2.00
|
1.05
|
2.03
|
| Title | Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Area Under the Curve (AUC0-24), Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation |
|---|---|
| Description | Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing, predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. |
| Time Frame | Cycle 1, Day 15 (QD dosing: predose [morning] and 0.5, 1, 2, 4, and 8 hours postdose; BID dosing: predose [morning] and 1, 2, 4, and 7 hours postdose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. |
| Measure Participants | 3 | 5 | 5 | 5 | 6 | 5 | 6 |
| Median (Full Range) [ng*hr/mL] |
26200
|
50400
|
40500
|
81000
|
107000
|
173000
|
115000
|
| Title | Numeric Rating Scale (NRS) for PVNS Symptoms Sum of Scores Through Cycle 2 (Efficacy Evaluable Population) - Dose Extension |
|---|---|
| Description | The NRS for PVNS Symptoms instrument is a 5-item self-administered questionnaire to assess the "worst" of each of the symptoms pain, swelling, stiffness, instability and limited motion in the last 24 hours. A 0 to 10 NRS is provided for each symptom. For pain, 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine". For the other 4 symptoms, 0 indicates "no (symptom)" and 10 indicates "(symptom) worst imaginable", e.g., "swelling - worst imaginable." Higher scores indicated worse outcome. |
| Time Frame | Baseline, Cycle 1 Day 15, Cycle 2, Cycle 3, Cycle 12, Cycle 24, Cycle 36, and Cycle 46 (each cycle was 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| NRS for PVNS symptoms were assessed in patients with available data in the Efficacy Evaluable Population. |
| Arm/Group Title | NRS for PVNS Symptoms Evaluable Population |
|---|---|
| Arm/Group Description | Participants who were administered the NRS scale at baseline and monthly on treatment. |
| Measure Participants | 21 |
| Pain; Baseline |
5.2
(2.1)
|
| Pain; Cycle 1 Day 15 |
3.5
(2.9)
|
| Pain; Cycle 2 |
3.6
(2.6)
|
| Pain; Cycle 3 |
2.3
(1.9)
|
| Pain; Cycle 12 |
1.3
(1.8)
|
| Pain; Cycle 24 |
1.5
(1.4)
|
| Pain; Cycle 36 |
2.0
(2.8)
|
| Pain; Cycle 46 |
1.8
(2.0)
|
| Swelling; Baseline |
4.7
(2.9)
|
| Swelling; Cycle 1 Day 15 |
3.1
(2.5)
|
| Swelling; Cycle 2 |
2.6
(2.3)
|
| Swelling; Cycle 3 |
1.5
(1.4)
|
| Swelling; Cycle 12 |
0.8
(1.2)
|
| Swelling; Cycle 24 |
0.8
(0.8)
|
| Swelling; Cycle 36 |
1.2
(1.8)
|
| Swelling; Cycle 46 |
1.1
(1.2)
|
| Stiffness; Baseline |
4.7
(2.9)
|
| Stiffness; Cycle 1 Day 15 |
3.6
(2.9)
|
| Stiffness; Cycle 2 |
3.1
(2.7)
|
| Stiffness; Cycle 3 |
2.2
(1.9)
|
| Stiffness; Cycle 12 |
1.5
(1.9)
|
| Stiffness; Cycle 24 |
1.2
(1.1)
|
| Stiffness; Cycle 36 |
1.6
(2.1)
|
| Stiffness; Cycle 46 |
1.6
(1.6)
|
| Instability; Baseline |
2.9
(2.6)
|
| Instability; Cycle 1 Day 15 |
2.1
(2.6)
|
| Instability; Cycle 2 |
2.1
(2.5)
|
| Instability; Cycle 3 |
1.2
(1.4)
|
| Instability; Cycle 12 |
0.8
(1.0)
|
| Instability; Cycle 24 |
0.4
(0.7)
|
| Instability; Cycle 36 |
0.4
(0.7)
|
| Instability; Cycle 46 |
0.4
(0.7)
|
| Limited motion; Baseline |
4.8
(2.8)
|
| Limited motion; Cycle 1 Day 15 |
3.2
(2.7)
|
| Limited motion; Cycle 2 |
3.0
(2.4)
|
| Limited motion; Cycle 3 |
1.9
(1.7)
|
| Limited motion; Cycle 12 |
1.4
(1.7)
|
| Limited motion; Cycle 24 |
1.0
(1.0)
|
| Limited motion; Cycle 36 |
1.7
(2.3)
|
| Limited Motion; Cycle 46 |
1.8
(1.7)
|
Adverse Events
| Time Frame | Adverse events (and serious adverse events) were recorded from the time the participant received the first dose of study drug up to 30 days after the last dose, up to approximately 30 months postdose. | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||
| Arm/Group Title | Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | MEC Cohort 1000 mg/Day (600mg AM, 400mg PM) | PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM) | GIST Cohort 1000 mg/Day (600mg AM, 400mg PM) | ATC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM) | Other Solid Tumor Type Cohort 1000 mg/Day (600mg AM, 400mg PM) | |||||||||||||
| Arm/Group Description | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. | Participants with advanced or recurrent mucoepidermoid carcinoma (MEC) who received PLX3397. | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. | Participants with advanced gastrointestinal stromal tumor (GIST) who received PLX3397. | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. | Participants with advanced solid tumors with malignant effusion who received PLX3397. | Participants with other solid tumor types who received PLX3397. | |||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||
| Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | MEC Cohort 1000 mg/Day (600mg AM, 400mg PM) | PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM) | GIST Cohort 1000 mg/Day (600mg AM, 400mg PM) | ATC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM) | Other Solid Tumor Type Cohort 1000 mg/Day (600mg AM, 400mg PM) | ||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 3/11 (27.3%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||
| Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | MEC Cohort 1000 mg/Day (600mg AM, 400mg PM) | PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM) | GIST Cohort 1000 mg/Day (600mg AM, 400mg PM) | ATC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM) | Other Solid Tumor Type Cohort 1000 mg/Day (600mg AM, 400mg PM) | ||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/6 (16.7%) | 3/7 (42.9%) | 2/4 (50%) | 5/39 (12.8%) | 4/11 (36.4%) | 1/9 (11.1%) | 2/8 (25%) | 3/20 (15%) | |||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||
| Febrile neutropenia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||
| Ascites | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Haematochezia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Small intestinal obstruction | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Diarrhoea | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| General disorders | ||||||||||||||||||||||||||
| Pyrexia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||||
| Cholecystitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hepatic haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||
| Pneumonia | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Bacterial sepsis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Cellulitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Clostridium difficile colitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Sepsis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Upper respiratory tract infection | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Investigations | ||||||||||||||||||||||||||
| Transaminases increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||
| Dehydration | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Hyponatraemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 4/39 (10.3%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Hypoglycaemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypomagnesaemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||
| Neck pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 3/20 (15%) | |||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||
| Renal cell carcinoma | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||
| Cerebrovascular accident | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Dizziness | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||
| Mental status changes | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||
| Renal failure acute | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||
| Acute respiratory failure | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypoxia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Pleural effusion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||
| Dose Escalation Cohort 1: 200 mg QD | Dose Escalation Cohort 2: 300 mg QD | Dose Escalation Cohort 3: 400 mg QD | Dose Escalation Cohort 4: 600 mg QD | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | MEC Cohort 1000 mg/Day (600mg AM, 400mg PM) | PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM) | GIST Cohort 1000 mg/Day (600mg AM, 400mg PM) | ATC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM) | Other Solid Tumor Type Cohort 1000 mg/Day (600mg AM, 400mg PM) | ||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 6/7 (85.7%) | 6/6 (100%) | 7/7 (100%) | 4/4 (100%) | 39/39 (100%) | 11/11 (100%) | 8/9 (88.9%) | 8/8 (100%) | 20/20 (100%) | |||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||
| Anaemia | 0/3 (0%) | 3/6 (50%) | 4/6 (66.7%) | 3/6 (50%) | 2/7 (28.6%) | 3/6 (50%) | 2/7 (28.6%) | 0/4 (0%) | 10/39 (25.6%) | 3/11 (27.3%) | 0/9 (0%) | 2/8 (25%) | 6/20 (30%) | |||||||||||||
| Neutropenia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Thrombocytopenia | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Leukocytosis | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Lymphadenopathy | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Leukopenia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Lymphopenia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Febrile neutropenia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||
| Angina pectoris | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Tachycardia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Palpitations | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 2/9 (22.2%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Electromechanical dissociation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Sinus bradycardia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Bundle branch block right | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||
| Tinnitus | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Ear discomfort | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||||
| Hypothyroidism | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Eye disorders | ||||||||||||||||||||||||||
| Conjunctival haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 1/9 (11.1%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Eye discharge | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Orbital oedema | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Vision blurred | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 6/39 (15.4%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Visual impairment | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Diplopia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Eye irritation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Eye pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Eye pruritus | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Myodesopsia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Dry eye | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Exophthalmos | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||
| Nausea | 1/3 (33.3%) | 3/6 (50%) | 3/6 (50%) | 4/6 (66.7%) | 4/7 (57.1%) | 2/6 (33.3%) | 2/7 (28.6%) | 1/4 (25%) | 26/39 (66.7%) | 4/11 (36.4%) | 3/9 (33.3%) | 5/8 (62.5%) | 9/20 (45%) | |||||||||||||
| Diarrhoea | 0/3 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 2/6 (33.3%) | 0/7 (0%) | 2/6 (33.3%) | 2/7 (28.6%) | 2/4 (50%) | 16/39 (41%) | 4/11 (36.4%) | 2/9 (22.2%) | 3/8 (37.5%) | 2/20 (10%) | |||||||||||||
| Vomiting | 1/3 (33.3%) | 3/6 (50%) | 2/6 (33.3%) | 3/6 (50%) | 3/7 (42.9%) | 1/6 (16.7%) | 3/7 (42.9%) | 1/4 (25%) | 14/39 (35.9%) | 1/11 (9.1%) | 3/9 (33.3%) | 2/8 (25%) | 7/20 (35%) | |||||||||||||
| Dry mouth | 0/3 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 4/39 (10.3%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Constipation | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 3/7 (42.9%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 11/39 (28.2%) | 2/11 (18.2%) | 4/9 (44.4%) | 3/8 (37.5%) | 6/20 (30%) | |||||||||||||
| Abdominal pain upper | 1/3 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 2/6 (33.3%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 3/39 (7.7%) | 2/11 (18.2%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Abdominal distension | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 3/39 (7.7%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Abdominal pain | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 2/39 (5.1%) | 4/11 (36.4%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Dyspepsia | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Retching | 1/3 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Ascites | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Stomatitis | 1/3 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Abdominal discomfort | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Abdominal pain lower | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Aphthous stomatitis | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Eructation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Faecal incontinence | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Flatulence | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Gingival bleeding | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Haematemesis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Oesophageal stenosis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Proctalgia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Rectal haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Toothache | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Dysphagia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 2/9 (22.2%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Gingival pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Haematochezia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Haemorrhoids | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Small intestine obstruction | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Tooth discolouration | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Upper gastrointestinal haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Diverticulum | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| General disorders | ||||||||||||||||||||||||||
| Fatigue | 0/3 (0%) | 3/6 (50%) | 1/6 (16.7%) | 3/6 (50%) | 5/7 (71.4%) | 2/6 (33.3%) | 3/7 (42.9%) | 2/4 (50%) | 36/39 (92.3%) | 7/11 (63.6%) | 5/9 (55.6%) | 6/8 (75%) | 12/20 (60%) | |||||||||||||
| Oedema peripheral | 1/3 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 15/39 (38.5%) | 2/11 (18.2%) | 2/9 (22.2%) | 0/8 (0%) | 3/20 (15%) | |||||||||||||
| Face oedema | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/4 (0%) | 6/39 (15.4%) | 0/11 (0%) | 2/9 (22.2%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Mucosal inflammation | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 2/8 (25%) | 0/20 (0%) | |||||||||||||
| Swelling face | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Pyrexia | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/7 (0%) | 2/6 (33.3%) | 1/7 (14.3%) | 0/4 (0%) | 2/39 (5.1%) | 1/11 (9.1%) | 1/9 (11.1%) | 1/8 (12.5%) | 2/20 (10%) | |||||||||||||
| Chest pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/4 (0%) | 2/39 (5.1%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Chills | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 2/11 (18.2%) | 1/9 (11.1%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Asthenia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 2/11 (18.2%) | 0/9 (0%) | 1/8 (12.5%) | 2/20 (10%) | |||||||||||||
| Chest discomfort | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Infusion site pain | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Non-cardiac chest pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Influenza like illness | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Early satiety | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Feeling abnormal | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Gait disturbance | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Oedema | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||||
| Hepatic haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hepatic steatosis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Immune system disorders | ||||||||||||||||||||||||||
| Hypersensitivity | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||
| Upper respiratory tract infection | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/6 (16.7%) | 2/7 (28.6%) | 0/4 (0%) | 6/39 (15.4%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 3/20 (15%) | |||||||||||||
| Oral candidiasis | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Pneumonia | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 1/8 (12.5%) | 2/20 (10%) | |||||||||||||
| Sinusitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Bronchitis | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Bronchitis viral | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Folliculitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Nasopharyngitis | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 4/39 (10.3%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Oesophageal candidiasis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Pharyngitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Sepsis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Urinary tract infection | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 3/11 (27.3%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Influenza | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Candidiasis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Cellulitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Lung infection | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Oral herpes | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Bacterial sepsis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Clostridium difficile colitis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Peritonitis bacterial | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Fungal skin infection | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||
| Contusion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Excoriation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Fall | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Seroma | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Sunburn | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Thermal burn | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Anaphylactic transfusion reaction | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Investigations | ||||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 9/39 (23.1%) | 1/11 (9.1%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/7 (14.3%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/4 (0%) | 9/39 (23.1%) | 2/11 (18.2%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Activated partial thromboplastin time prolonged | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Blood cholesterol increased | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 2/7 (28.6%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 2/11 (18.2%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Lymphocyte count decreased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| International normalised ratio increased | 0/3 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Weight decreased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 2/7 (28.6%) | 1/4 (25%) | 4/39 (10.3%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 4/20 (20%) | |||||||||||||
| Blood bilirubin increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Blood thyroid stimulating hormone increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Neutrophil count increased | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Occult blood positive | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Platelet count decreased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Prothrombin time prolonged | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| White blood cell count decreased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Lacrimation increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 1/11 (9.1%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Weight increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 6/39 (15.4%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Blood creatinine increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Blood creatinine phosphokinase increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Blood glucose decreased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Troponin increased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Neutrophil count decreased | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||
| Decreased appetite | 1/3 (33.3%) | 3/6 (50%) | 1/6 (16.7%) | 4/6 (66.7%) | 2/7 (28.6%) | 3/6 (50%) | 4/7 (57.1%) | 0/4 (0%) | 9/39 (23.1%) | 3/11 (27.3%) | 5/9 (55.6%) | 4/8 (50%) | 9/20 (45%) | |||||||||||||
| Hypophosphataemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 11/39 (28.2%) | 1/11 (9.1%) | 1/9 (11.1%) | 0/8 (0%) | 4/20 (20%) | |||||||||||||
| Dehydration | 1/3 (33.3%) | 3/6 (50%) | 1/6 (16.7%) | 2/6 (33.3%) | 1/7 (14.3%) | 0/6 (0%) | 2/7 (28.6%) | 0/4 (0%) | 3/39 (7.7%) | 1/11 (9.1%) | 1/9 (11.1%) | 1/8 (12.5%) | 2/20 (10%) | |||||||||||||
| Hyperglycaemia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypertriglyceridaemia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypokalaemia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 3/39 (7.7%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Abnormal loss of weight | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypercalcaemia | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hyponatraemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 2/8 (25%) | 1/20 (5%) | |||||||||||||
| Tumour lysis syndrome | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypomagnesaemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Fluid retention | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypercholesterolaemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypoalbuminaemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Hypoglycaemia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Malnutrition | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||
| Back pain | 2/3 (66.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 2/6 (33.3%) | 1/7 (14.3%) | 1/4 (25%) | 7/39 (17.9%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 4/20 (20%) | |||||||||||||
| Musculoskeletal pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 2/7 (28.6%) | 0/6 (0%) | 1/7 (14.3%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 4/20 (20%) | |||||||||||||
| Arthralgia | 1/3 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 24/39 (61.5%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 4/20 (20%) | |||||||||||||
| Myalgia | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Muscle spasms | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 4/39 (10.3%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Musculoskeletal chest pain | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Pain in extremity | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 11/39 (28.2%) | 0/11 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 2/20 (10%) | |||||||||||||
| Bone pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Bunion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Muscular weakness | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Joint swelling | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 7/39 (17.9%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Joint stiffness | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Arthritis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Fibromyalgia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Groin pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Muscle twitching | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Pain in jaw | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||
| Tumour pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Melanocytic naevus | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Tumour associated fever | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||
| Dysgeusia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 1/4 (25%) | 15/39 (38.5%) | 2/11 (18.2%) | 1/9 (11.1%) | 2/8 (25%) | 2/20 (10%) | |||||||||||||
| Headache | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 3/6 (50%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 13/39 (33.3%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 5/20 (25%) | |||||||||||||
| Cognitive disorder | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 7/39 (17.9%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Dizziness | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 2/6 (33.3%) | 1/7 (14.3%) | 1/6 (16.7%) | 2/7 (28.6%) | 1/4 (25%) | 11/39 (28.2%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Aphasia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Balance disorder | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Memory impairment | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Burning sensation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypoaesthesia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Hypogeusia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Lethargy | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Neuropathy peripheral | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 5/39 (12.8%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Paraesthesia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 4/39 (10.3%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Parosmia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Sedation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Syncope | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Tremor | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Amnesia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 4/39 (10.3%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Somnolence | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Disturbance in attention | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Migraine | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Cerebrovascular accident | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Mental impairment | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Presyncope | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||
| Insomnia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 7/39 (17.9%) | 4/11 (36.4%) | 2/9 (22.2%) | 2/8 (25%) | 2/20 (10%) | |||||||||||||
| Anxiety | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 5/39 (12.8%) | 1/11 (9.1%) | 1/9 (11.1%) | 0/8 (0%) | 3/20 (15%) | |||||||||||||
| Depression | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 2/6 (33.3%) | 0/7 (0%) | 1/4 (25%) | 5/39 (12.8%) | 1/11 (9.1%) | 2/9 (22.2%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Agitation | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Confusional state | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 1/4 (25%) | 3/39 (7.7%) | 1/11 (9.1%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Disorientation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Distractibility | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Impulsive behaviour | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Mental status changes | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Abnormal dreams | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hallucination | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Mood altered | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Sleep talking | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||
| Haematuria | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 5/39 (12.8%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hydronephrosis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Micturition urgency | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Nocturia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Pollakiuria | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Dysuria | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Proteinuria | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 2/8 (25%) | 0/20 (0%) | |||||||||||||
| Urinary incontinence | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||||||
| Breast mass | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Genital haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Pelvic pain | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Vaginal haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Menstruation irregular | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||
| Dyspnoea | 0/3 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 2/7 (28.6%) | 1/6 (16.7%) | 2/7 (28.6%) | 1/4 (25%) | 2/39 (5.1%) | 0/11 (0%) | 2/9 (22.2%) | 3/8 (37.5%) | 7/20 (35%) | |||||||||||||
| Cough | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 1/4 (25%) | 8/39 (20.5%) | 1/11 (9.1%) | 3/9 (33.3%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Dysphonia | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 2/9 (22.2%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Epistaxis | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Haemoptysis | 1/3 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Oropharyngeal pain | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Aspiration | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Bronchial obstruction | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hiccups | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Nasal congestion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 6/39 (15.4%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Paranasal sinus hypersecretion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Sinus congestion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Tachypnoea | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Pleural effusion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Hypoxia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Productive cough | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 2/11 (18.2%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Dyspnoea exertional | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Wheezing | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Acute respiratory failure | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Apnoea | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Interstitial lung disease | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Nasal septum ulceration | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Rhinorrhoea | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||
| Hair colour changes | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/7 (28.6%) | 2/6 (33.3%) | 3/7 (42.9%) | 1/4 (25%) | 28/39 (71.8%) | 4/11 (36.4%) | 0/9 (0%) | 1/8 (12.5%) | 10/20 (50%) | |||||||||||||
| Periorbital oedema | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/4 (25%) | 15/39 (38.5%) | 1/11 (9.1%) | 1/9 (11.1%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Pruritus | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/4 (0%) | 14/39 (35.9%) | 0/11 (0%) | 0/9 (0%) | 2/8 (25%) | 4/20 (20%) | |||||||||||||
| Rash | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/4 (0%) | 11/39 (28.2%) | 2/11 (18.2%) | 0/9 (0%) | 2/8 (25%) | 1/20 (5%) | |||||||||||||
| Rash maculo-papular | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 8/39 (20.5%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Skin hypopigmentation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 7/39 (17.9%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Photosensitivity reaction | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 2/20 (10%) | |||||||||||||
| Dry skin | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 5/39 (12.8%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Dermatitis acneiform | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 4/39 (10.3%) | 0/11 (0%) | 1/9 (11.1%) | 2/8 (25%) | 0/20 (0%) | |||||||||||||
| Night sweats | 0/3 (0%) | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Alopecia | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Erythema | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 9/39 (23.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Blister | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Ecchymosis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Erythema multiforme | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Increased tendency to bruise | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Onychoclasis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Pain of skin | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Petechiae | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Rash erythematous | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Rash generalised | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Urticaria | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Hair growth abnormal | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/20 (5%) | |||||||||||||
| Hyperhidrosis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Rash macular | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Skin depigmentation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Acne | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 3/39 (7.7%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Blood blister | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Dermatitis atopic | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Skin lesion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Hyperkeratosis | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Palmar erythema | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Rosacea | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/20 (0%) | |||||||||||||
| Skin hyperpigmentation | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hair texture abnormal | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||
| Hypertension | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 8/39 (20.5%) | 1/11 (9.1%) | 1/9 (11.1%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hypotension | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 1/39 (2.6%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Flushing | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 4/39 (10.3%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
| Hot flush | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 2/39 (5.1%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 1/20 (5%) | |||||||||||||
| Pallor | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 0/4 (0%) | 0/39 (0%) | 1/11 (9.1%) | 0/9 (0%) | 0/8 (0%) | 2/20 (10%) | |||||||||||||
| Superior vena caval occlusion | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/7 (0%) | 1/4 (25%) | 0/39 (0%) | 0/11 (0%) | 0/9 (0%) | 0/8 (0%) | 0/20 (0%) | |||||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Daiichi Sankyo Inc. |
| Phone | 908-992-6400 |
| CTRinfo@dsi.com |
Responsible Party:
Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier:
NCT01004861
Other Study ID Numbers:
- PLX108-01
First Posted:
Oct 30, 2009
Last Update Posted:
Jan 4, 2022
Last Verified:
Dec 1, 2021