Study Evaluating HKI-272 in Tumors
Sponsor
Puma Biotechnology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00146172
Collaborator
(none)
73
5
8
38
14.6
0.4
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability as well as find the maximum tolerated dose (MTD) for HKI-272. In addition, this study will examine the effects of the study drug on your tumor, and how your body uses and eliminates HKI-272.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
73 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
This trial was an open-label, phase 1, ascending single and multiple oral dose study of HKI-272 administered to subjects with erbB-2- or erbB-1-positive tumors. Each subject participated in only 1 dose group and received a single dose of test article, followed by a 1-week observation period, and then received the test article administered once daily by mouth for up to 6 months (6 cycles). Daily dose administration could continue beyond 6 cycles at the same dose level if HKI-272 was well tolerated and there was no evidence of progressive disease.This trial was an open-label, phase 1, ascending single and multiple oral dose study of HKI-272 administered to subjects with erbB-2- or erbB-1-positive tumors. Each subject participated in only 1 dose group and received a single dose of test article, followed by a 1-week observation period, and then received the test article administered once daily by mouth for up to 6 months (6 cycles). Daily dose administration could continue beyond 6 cycles at the same dose level if HKI-272 was well tolerated and there was no evidence of progressive disease.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Ascending Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HKI-272 Administered Orally to Subjects With HER-2/NEU or HER-1/EGFR-Positive Tumors
Actual Study Start Date
:
Nov 1, 2003
Actual Primary Completion Date
:
Jan 1, 2007
Actual Study Completion Date
:
Jan 1, 2007
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Neratinib 40 mg
|
Drug: neratinib
HKI-272
|
| Experimental: Neratinib 80 mg
|
Drug: neratinib
HKI-272
|
| Experimental: Neratinib 120 mg
|
Drug: neratinib
HKI-272
|
| Experimental: Neratinib 180 mg
|
Drug: neratinib
HKI-272
|
| Experimental: Neratinib 240 mg
|
Drug: neratinib
HKI-272
|
| Experimental: Neratinib 320 mg
|
Drug: neratinib
HKI-272
|
| Experimental: Neratinib 400 mg
|
Drug: neratinib
HKI-272
|
| Experimental: Neratinib 320 mg MTD
|
Drug: neratinib
HKI-272
|
Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicity (DLT) [From first dose date to day 14]
DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration.
- Maximum Tolerated Dose (MTD) [From first dose date to day 14]
If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD.
Secondary Outcome Measures
- Number of Participants With Best Overall Response [From first dose date to progression or last tumor assessment, up to 39 weeks.]
Best Overall response by tumor type, evaluable population per Response Evaluation Criteria In Solid Tumors Criteria v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in sum of the longest diameter (LD) of target lesions in reference to baseline sum of LD of target lesions; Progressive Disease (PD), >=20% increase in sum of LD of target lesions, taking as reference the smallest sum of recorded LD of target lesions since treatment started or appearance of 1 or more new lesions; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD of target lesions since the treatment start. The best overall response was the best response recorded from start of treatment until PD/recurrence. In general, the subject's best response assignment depended on achievement of both measurement and confirmation criteria.
- Duration of Response [From start date of response to first PD, up to 39 weeks.]
Duration of response of responders (PR+) by Kaplan-Meier estimate
- Progression Free Survival [From first dose date to progression or death, up to 39 weeks.]
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Objective Response Rate [From first dose date to progression/death or last assessment, up to 39 weeks]
Patients with PR or higher responses, evaluable population
- Clinical Benefit Rate [From first dose date to progression/death or last assessment, up to 39 weeks.]
Patients with PR or higher responses or SD>=24 weeks, evaluable population
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Her2/neu or Her1/EGFR positive cancer
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
-
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
Exclusion Criteria:
-
Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent of greater than 300 mg/m^2
-
Patients with significant cardiac risk factors
-
Active central nervous system metastasis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | H. Lee Moffitt Cancer Center & Research Institute | Tampa | Florida | United States | 33612 |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 3 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 4 | The Cleveland Clinic Foundation Taussig Cancer Center | Cleveland | Ohio | United States | 44195 |
| 5 | The Sarah Cannon Cancer Center | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Puma Biotechnology, Inc.
Investigators
- Study Director: Puma, Biotechnology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT00146172
Other Study ID Numbers:
- 3144A1-102
First Posted:
Sep 5, 2005
Last Update Posted:
Sep 17, 2018
Last Verified:
Aug 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Puma Biotechnology, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg | Neratinib MTD |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Neratinb 40 mg qd | Neratinib 80 mg qd | Neratinib 120 mg qd | Neratinib 180 mg qd | Neratinib 240 mg qd | Neratinib 320 mg qd | Neratinib 400 mg qd | Neratinib maximum tolerated dose (320 mg). |
| Period Title: Overall Study | ||||||||
| STARTED | 3 | 4 | 4 | 6 | 3 | 7 | 6 | 40 |
| Received Drug | 3 | 4 | 4 | 6 | 3 | 7 | 6 | 39 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 4 | 4 | 6 | 3 | 7 | 6 | 40 |
Baseline Characteristics
| Arm/Group Title | Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg | Neratinib MTD | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Neratinb 40 mg qd | Neratinib 80 mg qd | Neratinib 120 mg qd | Neratinib 180 mg qd | Neratinib 240 mg qd | Neratinib 320 mg qd | Neratinib 400 mg qd | Neratinib maximum tolerated dose (320 mg) from part 2. | Total of all reporting groups |
| Overall Participants | 3 | 4 | 4 | 6 | 3 | 7 | 6 | 39 | 72 |
| Age (Count of Participants) | |||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
3
100%
|
4
100%
|
2
50%
|
5
83.3%
|
3
100%
|
3
42.9%
|
6
100%
|
28
71.8%
|
54
75%
|
| >=65 years |
0
0%
|
0
0%
|
2
50%
|
1
16.7%
|
0
0%
|
4
57.1%
|
0
0%
|
11
28.2%
|
18
25%
|
| Age (years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [years] |
51.33
(12.50)
|
54.00
(7.66)
|
56.25
(20.43)
|
60.67
(15.31)
|
57.00
(8.89)
|
63.71
(15.70)
|
51.33
(8.91)
|
58.18
(11.05)
|
57.68
(12.06)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
2
66.7%
|
4
100%
|
3
75%
|
6
100%
|
2
66.7%
|
5
71.4%
|
4
66.7%
|
26
66.7%
|
52
72.2%
|
| Male |
1
33.3%
|
0
0%
|
1
25%
|
0
0%
|
1
33.3%
|
2
28.6%
|
2
33.3%
|
13
33.3%
|
20
27.8%
|
Outcome Measures
| Title | Dose Limiting Toxicity (DLT) |
|---|---|
| Description | DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration. |
| Time Frame | From first dose date to day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the dosing groups 40 mg through 400 mg, excluding the selection of MTD. |
| Arm/Group Title | Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Neratinb 40 mg qd | Neratinib 80 mg qd | Neratinib 120 mg qd | Neratinib 180 mg qd | Neratinib 240 mg qd | Neratinib 320 mg qd. | Neratinib 400 mg qd |
| Measure Participants | 3 | 4 | 4 | 6 | 3 | 7 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
4
66.7%
|
| Title | Number of Participants With Best Overall Response |
|---|---|
| Description | Best Overall response by tumor type, evaluable population per Response Evaluation Criteria In Solid Tumors Criteria v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in sum of the longest diameter (LD) of target lesions in reference to baseline sum of LD of target lesions; Progressive Disease (PD), >=20% increase in sum of LD of target lesions, taking as reference the smallest sum of recorded LD of target lesions since treatment started or appearance of 1 or more new lesions; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD of target lesions since the treatment start. The best overall response was the best response recorded from start of treatment until PD/recurrence. In general, the subject's best response assignment depended on achievement of both measurement and confirmation criteria. |
| Time Frame | From first dose date to progression or last tumor assessment, up to 39 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who had received at least 14 days of continuous dose administration of test article and who had undergone at least 1 follow-up tumor assessment, evaluable population |
| Arm/Group Title | Breast Cancer Cohort | Lung Cancer Cohort | All Subjects |
|---|---|---|---|
| Arm/Group Description | Subjects with Breast Cancer | Subjects with Lung Cancer | Subjects with Cancer |
| Measure Participants | 25 | 14 | 60 |
| Partial Response |
8
266.7%
|
0
0%
|
8
200%
|
| Stable Disease >=24 weeks |
1
33.3%
|
6
150%
|
7
175%
|
| Stable Disease >=16 weeks |
1
33.3%
|
0
0%
|
4
100%
|
| Stable Disease >=8 weeks |
4
133.3%
|
2
50%
|
9
225%
|
| Progressive Disease |
11
366.7%
|
6
150%
|
32
800%
|
| Title | Duration of Response |
|---|---|
| Description | Duration of response of responders (PR+) by Kaplan-Meier estimate |
| Time Frame | From start date of response to first PD, up to 39 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects responses classified as complete response or partial response in evaluable population |
| Arm/Group Title | Breast Cancer | Lung Cancer | All Subjects |
|---|---|---|---|
| Arm/Group Description | Subjects with Breast Cancer | Subjects with Lung Cancer | Subjects with Cancer |
| Measure Participants | 8 | 0 | 8 |
| Median (95% Confidence Interval) [months] |
4.8
|
4.8
|
| Title | Progression Free Survival |
|---|---|
| Description | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Time Frame | From first dose date to progression or death, up to 39 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who were assigned to treatment, received at least 14 days of continuous dose administration of test article, and who had undergone at least 1 follow-up tumor assessment, evaluable population |
| Arm/Group Title | Breast Cancer | Lung Cancer | All Subjects |
|---|---|---|---|
| Arm/Group Description | Subjects with Breast Cancer | Subjects with Lung Cancer | Subjects with Cancer |
| Measure Participants | 25 | 14 | 60 |
| Median (95% Confidence Interval) [months] |
3.6
|
3.5
|
1.9
|
| Title | Objective Response Rate |
|---|---|
| Description | Patients with PR or higher responses, evaluable population |
| Time Frame | From first dose date to progression/death or last assessment, up to 39 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Breast, Lung and other solid tumors included in the efficacy evaluable population |
| Arm/Group Title | Breast Cancer | Lung Cancer | All Solid Tumors |
|---|---|---|---|
| Arm/Group Description | Subjects with breast cancer in all doses of neratinib | Subjects with Lung cancer in all doses of Neratinib | Subjects with solid tumors in all doses of Neratinib |
| Measure Participants | 25 | 14 | 60 |
| Number (95% Confidence Interval) [percentage of participants] |
32.0
1066.7%
|
0
0%
|
13.3
332.5%
|
| Title | Clinical Benefit Rate |
|---|---|
| Description | Patients with PR or higher responses or SD>=24 weeks, evaluable population |
| Time Frame | From first dose date to progression/death or last assessment, up to 39 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Breast, Lung and other solid tumors included in the efficacy evaluable population |
| Arm/Group Title | Breast Cancer | Lung Cancer | All Solid Tumors |
|---|---|---|---|
| Arm/Group Description | Subjects with breast cancer in all doses of neratinib | Subjects with Lung cancer in all doses of Neratinib | Subjects with solid tumors in all doses of Neratinib |
| Measure Participants | 25 | 14 | 60 |
| Number (95% Confidence Interval) [percentage of participants] |
36.0
1200%
|
42.9
1072.5%
|
25.0
625%
|
| Title | Maximum Tolerated Dose (MTD) |
|---|---|
| Description | If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD. |
| Time Frame | From first dose date to day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients receiving neratinib in the dose escalation part of the study. |
| Arm/Group Title | Neratinib 320 mg |
|---|---|
| Arm/Group Description | Neratinib 320 mg qd |
| Measure Participants | 33 |
| Number [mg] |
320
|
Adverse Events
| Time Frame | From first dose through 28 days after last dose, up to 39 weeks. | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||
| Arm/Group Title | Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg | Neratinib MTD | ||||||||
| Arm/Group Description | Neratinb 40 mg qd | Neratinib 80 mg qd | Neratinib 120 mg qd | Neratinib 180 mg qd | Neratinib 240 mg qd | Neratinib 320 mg qd | Neratinib 400 mg qd | Neratinib maximum tolerated dose (320 mg). | ||||||||
All Cause Mortality |
||||||||||||||||
| Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg | Neratinib MTD | |||||||||
| 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg | Neratinib MTD | |||||||||
| 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%) | 1/4 (25%) | 1/4 (25%) | 2/6 (33.3%) | 0/3 (0%) | 4/7 (57.1%) | 2/6 (33.3%) | 14/39 (35.9%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Cardiac disorders | ||||||||||||||||
| Cardio-respiratory arrest | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Tachycardia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Eye disorders | ||||||||||||||||
| Papilloedema | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Photophobia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Vitreous haemorrhage | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal distension | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Abdominal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Ascites | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Diarrhoea | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Nausea | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Small intestinal obstruction | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Vomiting | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| General disorders | ||||||||||||||||
| Asthenia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Chest pain | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Pyrexia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Infections and infestations | ||||||||||||||||
| Cellulitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Pharyngitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Pneumonia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Viral infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Hip fracture | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Investigations | ||||||||||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Aspartate aminotransferase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Decreased appetite | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Dehydration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Back pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Pain in extremity | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Breast cancer | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Breast cancer metastatic | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Colon cancer metastatic | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Glioblastoma | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Lung neoplasm malignant | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Metastatic squamous cell carcinoma | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Neoplasm malignant | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Non-small cell lung cancer | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Ovarian cancer | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Ovarian cancer metastatic | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Nervous system disorders | ||||||||||||||||
| Convulsion | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Peripheral motor neuropathy | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Speech disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Psychiatric disorders | ||||||||||||||||
| Anxiety | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Confusional state | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Dyspnoea | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 5 |
| Pleural effusion | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Pneumonitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Pneumothorax | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Respiratory arrest | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Erythema | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Pruritus | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Urticaria | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg | Neratinib MTD | |||||||||
| 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%) | 4/4 (100%) | 4/4 (100%) | 6/6 (100%) | 3/3 (100%) | 7/7 (100%) | 6/6 (100%) | 39/39 (100%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 4 | 2/7 (28.6%) | 10 | 0/6 (0%) | 0 | 5/39 (12.8%) | 20 |
| Leukopenia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/6 (33.3%) | 3 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 4 |
| Lymphopenia | 0/3 (0%) | 0 | 2/4 (50%) | 3 | 1/4 (25%) | 6 | 2/6 (33.3%) | 9 | 1/3 (33.3%) | 3 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Thrombocytopenia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| Arrhythmia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Bundle branch block left | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Palpitations | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Sinus tachycardia | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Supraventricular tachycardia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Tachycardia | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Eye disorders | ||||||||||||||||
| Cataract | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/39 (5.1%) | 2 |
| Corneal opacity | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Diplopia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Dry eye | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Photophobia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Photopsia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Retinal artery occlusion | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Vision blurred | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal distension | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 3 |
| Abdominal pain | 2/3 (66.7%) | 3 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 4/7 (57.1%) | 6 | 1/6 (16.7%) | 1 | 8/39 (20.5%) | 17 |
| Abdominal pain lower | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Abdominal pain upper | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 2 | 1/6 (16.7%) | 1 | 3/39 (7.7%) | 4 |
| Constipation | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 2/4 (50%) | 4 | 1/6 (16.7%) | 3 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 4 | 5/39 (12.8%) | 7 |
| Diarrhoea | 1/3 (33.3%) | 3 | 2/4 (50%) | 5 | 3/4 (75%) | 13 | 6/6 (100%) | 26 | 3/3 (100%) | 19 | 7/7 (100%) | 26 | 5/6 (83.3%) | 35 | 36/39 (92.3%) | 189 |
| Dry mouth | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 4/39 (10.3%) | 5 |
| Dyspepsia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 2/3 (66.7%) | 4 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 3/39 (7.7%) | 5 |
| Dysphagia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 3/39 (7.7%) | 6 |
| Faecal incontinence | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Flatulence | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 4/39 (10.3%) | 5 |
| Gastritis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Gastrooesophageal reflux disease | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Gingival bleeding | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 3 | 0/39 (0%) | 0 |
| Haematochezia | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Haemorrhoids | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Mouth haemorrhage | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Nausea | 2/3 (66.7%) | 2 | 3/4 (75%) | 4 | 4/4 (100%) | 12 | 3/6 (50%) | 11 | 3/3 (100%) | 7 | 5/7 (71.4%) | 16 | 6/6 (100%) | 16 | 21/39 (53.8%) | 47 |
| Oesophageal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/39 (0%) | 0 |
| Oesophagitis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Toothache | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Vomiting | 1/3 (33.3%) | 3 | 1/4 (25%) | 3 | 2/4 (50%) | 6 | 2/6 (33.3%) | 5 | 2/3 (66.7%) | 11 | 3/7 (42.9%) | 8 | 6/6 (100%) | 12 | 19/39 (48.7%) | 43 |
| General disorders | ||||||||||||||||
| Asthenia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 2 | 1/6 (16.7%) | 1 | 2/39 (5.1%) | 7 |
| Axillary pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Chest discomfort | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 4 | 1/39 (2.6%) | 1 |
| Chest pain | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 1/39 (2.6%) | 1 |
| Chills | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/4 (50%) | 7 | 2/6 (33.3%) | 2 | 1/3 (33.3%) | 1 | 2/7 (28.6%) | 3 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Early satiety | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Face oedema | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/39 (2.6%) | 2 |
| Fatigue | 3/3 (100%) | 7 | 3/4 (75%) | 4 | 3/4 (75%) | 6 | 4/6 (66.7%) | 5 | 2/3 (66.7%) | 3 | 6/7 (85.7%) | 13 | 5/6 (83.3%) | 11 | 19/39 (48.7%) | 47 |
| General physical health deterioration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Local swelling | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Localised oedema | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Malaise | 1/3 (33.3%) | 3 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 4 |
| Mucosal inflammation | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Oedema | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Oedema peripheral | 2/3 (66.7%) | 5 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 4/39 (10.3%) | 9 |
| Pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Performance status decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Pyrexia | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/7 (14.3%) | 3 | 1/6 (16.7%) | 3 | 3/39 (7.7%) | 4 |
| Infections and infestations | ||||||||||||||||
| Bronchitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 3 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Herpes zoster | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Nail bed infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Nasopharyngitis | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Pharyngitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Tinea infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Upper respiratory tract infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 3 | 2/39 (5.1%) | 4 |
| Urinary tract infection | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 2/6 (33.3%) | 2 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 8 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Excoriation | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Fall | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Thermal burn | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Investigations | ||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Alanine aminotransferase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/6 (33.3%) | 11 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 6/39 (15.4%) | 15 |
| Aspartate aminotransferase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 3/6 (50%) | 8 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 6/39 (15.4%) | 9 |
| Blood alkaline phosphatase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/6 (33.3%) | 2 | 1/3 (33.3%) | 1 | 2/7 (28.6%) | 2 | 1/6 (16.7%) | 1 | 7/39 (17.9%) | 9 |
| Blood chloride decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 6 |
| Blood creatinine increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Blood phosphorus increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Blood thyroid stimulating hormone increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Blood triglycerides increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Blood urea increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Electrocardiogram QT prolonged | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Electrocardiogram ST-T segment abnormal | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Electrocardiogram T wave abnormal | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Haemoglobin decreased | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 2/6 (33.3%) | 3 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Weight decreased | 1/3 (33.3%) | 3 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 2/7 (28.6%) | 4 | 2/6 (33.3%) | 3 | 7/39 (17.9%) | 16 |
| Weight increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/39 (2.6%) | 4 |
| White blood cell count decreased | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| White blood cells urine positive | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Decreased appetite | 1/3 (33.3%) | 1 | 3/4 (75%) | 3 | 0/4 (0%) | 0 | 1/6 (16.7%) | 5 | 3/3 (100%) | 4 | 5/7 (71.4%) | 7 | 3/6 (50%) | 3 | 17/39 (43.6%) | 36 |
| Dehydration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 6/39 (15.4%) | 7 |
| Hypercalcaemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 2/3 (66.7%) | 5 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Hyperglycaemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 5 |
| Hyperkalaemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Hypernatraemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Hypertriglyceridaemia | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Hyperuricaemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 4 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Hypoalbuminaemia | 0/3 (0%) | 0 | 1/4 (25%) | 4 | 1/4 (25%) | 4 | 1/6 (16.7%) | 3 | 2/3 (66.7%) | 2 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Hypocalcaemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Hypoglycaemia | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Hypokalaemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 3/39 (7.7%) | 6 |
| Hypomagnesaemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 6 |
| Hyponatraemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Iron deficiency | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 2 | 1/6 (16.7%) | 4 | 6/39 (15.4%) | 24 |
| Back pain | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 2/6 (33.3%) | 3 | 0/3 (0%) | 0 | 2/7 (28.6%) | 4 | 0/6 (0%) | 0 | 3/39 (7.7%) | 7 |
| Bone pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Flank pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 5 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Muscle spasms | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 3 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 1/39 (2.6%) | 3 |
| Muscle tightness | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Muscular weakness | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 5 |
| Musculoskeletal chest pain | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 4 | 2/39 (5.1%) | 3 |
| Musculoskeletal discomfort | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Musculoskeletal pain | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 4 |
| Myalgia | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Osteoarthritis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Pain in extremity | 2/3 (66.7%) | 4 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 2/39 (5.1%) | 12 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Metastases to bone | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Tumour associated fever | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||
| Amnesia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 5 |
| Aphasia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Ataxia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 4 |
| Disturbance in attention | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/39 (0%) | 0 |
| Dizziness | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 6/39 (15.4%) | 13 |
| Dysgeusia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Headache | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 2/3 (66.7%) | 3 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 9/39 (23.1%) | 19 |
| Hypoaesthesia | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Memory impairment | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Migraine | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 4 | 1/6 (16.7%) | 1 | 1/39 (2.6%) | 1 |
| Neuropathy peripheral | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Somnolence | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Speech disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 4 |
| Psychiatric disorders | ||||||||||||||||
| Anxiety | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 1/6 (16.7%) | 1 | 1/39 (2.6%) | 2 |
| Confusional state | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Depression | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Insomnia | 1/3 (33.3%) | 2 | 2/4 (50%) | 3 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 1/3 (33.3%) | 2 | 1/7 (14.3%) | 3 | 1/6 (16.7%) | 1 | 3/39 (7.7%) | 4 |
| Mental status changes | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Mood swings | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Sleep disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||
| Nocturia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Pollakiuria | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/39 (5.1%) | 6 |
| Renal failure | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Breast swelling | 1/3 (33.3%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Menorrhagia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/39 (0%) | 0 |
| Penile swelling | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Scrotal swelling | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Vulvovaginal dryness | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Cough | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 1/3 (33.3%) | 2 | 0/7 (0%) | 0 | 2/6 (33.3%) | 6 | 9/39 (23.1%) | 15 |
| Dry throat | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Dysphonia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 1/39 (2.6%) | 2 |
| Dyspnoea | 2/3 (66.7%) | 6 | 2/4 (50%) | 2 | 2/4 (50%) | 5 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 2/7 (28.6%) | 6 | 2/6 (33.3%) | 8 | 10/39 (25.6%) | 14 |
| Dyspnoea exertional | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 3 | 0/39 (0%) | 0 |
| Epistaxis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Hiccups | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
| Lung infiltration | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Nasal congestion | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 1/6 (16.7%) | 2 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 5 |
| Pleural effusion | 2/3 (66.7%) | 3 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Pleurisy | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Pneumonitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/39 (0%) | 0 |
| Productive cough | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Pulmonary congestion | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Rhinorrhoea | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Sputum discoloured | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Throat irritation | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Upper-airway cough syndrome | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/39 (2.6%) | 2 |
| Wheezing | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/39 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Alopecia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/39 (0%) | 0 |
| Dermatitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Dermatitis acneiform | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 3 |
| Dermatitis contact | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Dry skin | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Erythema | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 4 |
| Hyperhidrosis | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Pruritus | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/39 (7.7%) | 3 |
| Rash | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 3/7 (42.9%) | 4 | 2/6 (33.3%) | 7 | 3/39 (7.7%) | 10 |
| Rash erythematous | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 2 | 1/6 (16.7%) | 2 | 1/39 (2.6%) | 2 |
| Rash papular | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Skin exfoliation | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Skin hyperpigmentation | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Skin mass | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Skin ulcer | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/39 (0%) | 0 |
| Vascular disorders | ||||||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/39 (2.6%) | 2 |
| Hot flush | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 2 | 0/6 (0%) | 0 | 1/39 (2.6%) | 1 |
| Orthostatic hypotension | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/39 (5.1%) | 2 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Senior Director, Clinical Operations |
|---|---|
| Organization | Puma Biotechnology, Inc. |
| Phone | +1 (424) 248-6500 |
| clinicaltrials@pumabiotechnology.com |
Responsible Party:
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT00146172
Other Study ID Numbers:
- 3144A1-102
First Posted:
Sep 5, 2005
Last Update Posted:
Sep 17, 2018
Last Verified:
Aug 1, 2018