SELECT-2: Assess Efficacy and Safety of AZD6244 in Combination With Docetaxel in Patients Receiving Second Line Non Small Cell Lung Cancer Treatment.
Sponsor
AstraZeneca (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01750281
Collaborator
(none)
212
51
3
120.4
4.2
0
Study Details
Study Description
Brief Summary
The purpose of this study is to treat patients with locally advanced or metastatic NSCLC with a combination therapy of selumetinib and two different doses of docetaxel 75mg/m2 or 60 mg/m2 vs placebo and compare how well each dose affects how their cancer responds. It will also help us to understand the tolerability profile of the different dosing regimens in these patients
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination with Docetaxel, Compared with Placebo in Combination with Docetaxel, in Patients receiving second line treatment for Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV)
Study Design
Study Type:
Interventional
Actual Enrollment
:
212 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, Compared With Placebo in Combination With Docetaxel, in Patients Receiving Second Line Treatment for Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV)
Actual Study Start Date
:
Dec 18, 2012
Actual Primary Completion Date
:
Jan 27, 2016
Anticipated Study Completion Date
:
Dec 30, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2 Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle. |
Drug: Selumetinib 75 mg
Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.
Drug: Docetaxel 75 mg/m2
Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
|
| Experimental: Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2 Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 60 mg/m2 intravenously administered on day 1 of each 21 day cycle. |
Drug: Selumetinib 75 mg
Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.
Drug: Docetaxel 60 mg/m2
Docetaxel 60 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
|
| Experimental: Placebo twice daily + Docetaxel 75 mg/m2 Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle. |
Drug: Docetaxel 75 mg/m2
Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
Drug: Placebo
Three placebo capsules will be administered orally uninterrupted twice daily.
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [Baseline and then every 6 weeks after randomization until objective disease progression, up to 29 months (at the time of the analysis)]
Median time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours (RECIST v1.1): >= 20% increase in the sum of diameters of Target Lesions (TL) and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of Non TLs or a new lesion.
Secondary Outcome Measures
- Overall Survival (OS) [Following progression, survival status was collected every 8 weeks until death, withdrawal of consent, or end of study, whichever occurred first, up to 29 months (at the time of the analysis)]
The time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Provision of signed, written and dated informed consent prior to any study specific procedures
-
Male or female, aged 18 years or older
-
Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
-
Prospective confirmation of KRAS mutation negative status as determined via an AZ approved laboratory
-
Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
Exclusion Criteria:
-
Mixed small cell and non-small cell lung cancer histology
-
Received >1 prior anti-cancer drug regimen for advanced or metastatic NSCLC. Patients who develop disease progression while on switch maintenance therapy (maintenance using an agent not in the first-line regimen) will not be eligible.
-
Other concomitant anti-cancer therapy agents except steroids
-
Prior treatment with a MEK (Mitogen-Activated Protein Kinase) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable)
-
The last radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Santa Monica | California | United States | 90904 |
| 2 | Research Site | Aurora | Colorado | United States | 80045 |
| 3 | Research Site | Hollywood | Florida | United States | 33028 |
| 4 | Research Site | Marrero | Louisiana | United States | 70072 |
| 5 | Research Site | Boston | Massachusetts | United States | 02215 |
| 6 | Research Site | Mineola | New York | United States | 11501 |
| 7 | Research Site | New York | New York | United States | 10032 |
| 8 | Research Site | Philadelphia | Pennsylvania | United States | 19107 |
| 9 | Research Site | Barretos | Brazil | 14784-400 | |
| 10 | Research Site | Ijui | Brazil | 98700-000 | |
| 11 | Research Site | Porto Alegre | Brazil | 90035-003 | |
| 12 | Research Site | Porto Alegre | Brazil | 90619-900 | |
| 13 | Research Site | Porto Alegre | Brazil | 91350-200 | |
| 14 | Research Site | Sao Paulo | Brazil | 01221-020 | |
| 15 | Research Site | Sao Paulo | Brazil | 01246-000 | |
| 16 | Research Site | São José do Rio Preto | Brazil | 15090-000 | |
| 17 | Research Site | São Paulo | Brazil | 04039-002 | |
| 18 | Research Site | Plovdiv | Bulgaria | 4000 | |
| 19 | Research Site | Plovdiv | Bulgaria | 4004 | |
| 20 | Research Site | Sofia | Bulgaria | 1233 | |
| 21 | Research Site | Sofia | Bulgaria | 1303 | |
| 22 | Research Site | Sofia | Bulgaria | 1756 | |
| 23 | Research Site | Varna | Bulgaria | 9010 | |
| 24 | Research Site | Vratza | Bulgaria | 3000 | |
| 25 | Research Site | Brest Cedex | France | 29609 | |
| 26 | Research Site | Caen | France | F-14033 | |
| 27 | Research Site | Clermont Ferrand | France | 63003 | |
| 28 | Research Site | Lille | France | 59000 | |
| 29 | Research Site | Pierre Benite Cedex | France | 69310 | |
| 30 | Research Site | Villejuif | France | 94805 | |
| 31 | Research Site | Essen | Germany | 45122 | |
| 32 | Research Site | Esslingen | Germany | 73730 | |
| 33 | Research Site | Großhansdorf | Germany | 22927 | |
| 34 | Research Site | Karlsruhe | Germany | 76137 | |
| 35 | Research Site | Löwenstein | Germany | 74245 | |
| 36 | Research Site | Moers | Germany | 47441 | |
| 37 | Research Site | Wiesbaden | Germany | 65199 | |
| 38 | Research Site | Würzburg | Germany | 97080 | |
| 39 | Research Site | Budapest | Hungary | 1121 | |
| 40 | Research Site | Budapest | Hungary | 1122 | |
| 41 | Research Site | Edelény | Hungary | 3780 | |
| 42 | Research Site | Kaposvár | Hungary | 7400 | |
| 43 | Research Site | Miskolc | Hungary | 3529 | |
| 44 | Research Site | Nyíregyháza | Hungary | 4400 | |
| 45 | Research Site | Székesfehérvár | Hungary | 8000 | |
| 46 | Research Site | Amsterdam | Netherlands | 1066 CX | |
| 47 | Research Site | Amsterdam | Netherlands | 1081 HV | |
| 48 | Research Site | Den Bosch | Netherlands | 5223 GZ | |
| 49 | Research Site | Maastricht | Netherlands | 6202 AZ | |
| 50 | Research Site | Grudziądz | Poland | 86-300 | |
| 51 | Research Site | Olsztyn | Poland | 10-357 |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Chair: Gabriella Mariani, MD, AstraZeneca UK, MSD
- Principal Investigator: Pasi Janne, MD, Dana-Farber Cancer Institute, USA
- Principal Investigator: Jean-Charles Soria, MD, Institut de Cancerology Gustave Roussy, France
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01750281
Other Study ID Numbers:
- D1532C00064
- 2012-003622-25
First Posted:
Dec 17, 2012
Last Update Posted:
Jul 6, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Initially the study protocol allowed patients with KRASm (KRAS mutation positive), KRAS NMD (No mutation detected) and KRAS mutation status unknown. Recruitment was put on hold after the 77th patient was randomised in September 2013, to allow a protocol amendment to include only patients with centrally confirmed KRAS NMD NSCLC to be enrolled. |
|---|---|
| Pre-assignment Detail | The Protocol Section "Enrolment Number" of 466 includes 1 patient who was pre-screened twice. Of the 465 unique "pre-screened" patients, 337 gave informed consent and of these, 212 were randomised. 211 received at least 1 dose of treatment and were included in the safety analysis set. Patients received selumetinib (AZD6244; ARRY-142886) or Placebo. |
| Arm/Group Title | Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Oral placebo BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle |
| Period Title: Overall Study | |||
| STARTED | 43 | 85 | 84 |
| Received Treatment | 43 | 84 | 84 |
| Did Not Receive Treatment | 0 | 1 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 43 | 85 | 84 |
Baseline Characteristics
| Arm/Group Title | Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 | Total |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle | Total of all reporting groups |
| Overall Participants | 43 | 85 | 84 | 212 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
63.6
(7.75)
|
62.4
(8.53)
|
60.4
(9.35)
|
61.8
(8.77)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
16
37.2%
|
19
22.4%
|
26
31%
|
61
28.8%
|
| Male |
27
62.8%
|
66
77.6%
|
58
69%
|
151
71.2%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||
| Black Or African American |
0
0%
|
5
5.9%
|
5
6%
|
10
4.7%
|
| Other |
2
4.7%
|
0
0%
|
1
1.2%
|
3
1.4%
|
| White |
41
95.3%
|
80
94.1%
|
78
92.9%
|
199
93.9%
|
| KRAS Mutation Status at Baseline (Number) [Number] | ||||
| KRAS no mutation detected (NMD) |
30
69.8%
|
62
72.9%
|
54
64.3%
|
146
68.9%
|
| KRAS mutation positive |
10
23.3%
|
15
17.6%
|
19
22.6%
|
44
20.8%
|
| KRAS mutation unknown |
3
7%
|
8
9.4%
|
11
13.1%
|
22
10.4%
|
Outcome Measures
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | Median time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours (RECIST v1.1): >= 20% increase in the sum of diameters of Target Lesions (TL) and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of Non TLs or a new lesion. |
| Time Frame | Baseline and then every 6 weeks after randomization until objective disease progression, up to 29 months (at the time of the analysis) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (All randomised patients). Progression events that do not occur within 14 weeks of the last evaluable assessement are censored and therefore excluded. |
| Arm/Group Title | Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Oral placebo BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle |
| Measure Participants | 36 | 75 | 69 |
| Median (Inter-Quartile Range) [Months] |
4.3
|
3.0
|
4.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo + Docetaxel 75 mg/m^2, Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | A hazard ratio <1 favours selumetinib in combination with docetaxel | |
| Statistical Test of Hypothesis | p-Value | 0.584 |
| Comments | ||
| Method | Cox Proportional Hazards | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.12 | |
| Confidence Interval |
(2-Sided) 90% 0.80 to 1.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo + Docetaxel 75 mg/m^2, Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | A hazard ratio <1 favours selumetinib in combination with docetaxel | |
| Statistical Test of Hypothesis | p-Value | 0.690 |
| Comments | ||
| Method | Cox Proportional Hazards | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.92 | |
| Confidence Interval |
(2-Sided) 90% 0.65 to 1.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) |
|---|---|
| Description | The time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive |
| Time Frame | Following progression, survival status was collected every 8 weeks until death, withdrawal of consent, or end of study, whichever occurred first, up to 29 months (at the time of the analysis) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (All randomised patients) |
| Arm/Group Title | Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Oral placebo BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle |
| Measure Participants | 26 | 64 | 57 |
| Median (Inter-Quartile Range) [Months] |
11.5
|
5.7
|
7.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo + Docetaxel 75 mg/m^2, Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | A hazard ratio <1 favours selumetinib in combination with docetaxel | |
| Statistical Test of Hypothesis | p-Value | 0.126 |
| Comments | ||
| Method | Cox Proportional Hazards | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.43 | |
| Confidence Interval |
(2-Sided) 90% 0.97 to 2.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo + Docetaxel 75 mg/m^2, Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | A hazard ratio <1 favours selumetinib in combination with docetaxel | |
| Statistical Test of Hypothesis | p-Value | 0.485 |
| Comments | ||
| Method | Cox Proportional Hazards | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.18 | |
| Confidence Interval |
(2-Sided) 90% 0.80 to 1.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 | |||
| Arm/Group Description | Oral placebo BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle | Oral selumetinib BD and intravenous docetaxel on day 1 of every 21 day cycle | |||
All Cause Mortality |
||||||
| Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/43 (37.2%) | 40/84 (47.6%) | 38/84 (45.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Febrile neutropenia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Neutropenia | 3/43 (7%) | 3 | 1/84 (1.2%) | 1 | 4/84 (4.8%) | 4 |
| Cardiac disorders | ||||||
| Cardiac arrest | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Cardiac failure | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Cardiac failure congestive | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Cardiac tamponade | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Chronic right ventricular failure | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Left ventricular dysfunction | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Left ventricular failure | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Colitis ischaemic | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Constipation | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Diarrhoea | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Dysphagia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Glossitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Haematemesis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Ileus | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Large intestine perforation | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Nausea | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Rectal haemorrhage | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Upper gastrointestinal haemorrhage | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Vomiting | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 3 |
| General disorders | ||||||
| Asthenia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Fatigue | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Generalised oedema | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Oedema peripheral | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Performance status decreased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Pyrexia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Hepatobiliary disorders | ||||||
| Cholestasis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hepatocellular injury | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Infections and infestations | ||||||
| Cellulitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Clostridium difficile infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Erysipelas | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Gastroenteritis salmonella | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Infection | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Infective exacerbation of chronic obstructive airways disease | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Lung infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pneumonia | 1/43 (2.3%) | 1 | 10/84 (11.9%) | 13 | 4/84 (4.8%) | 4 |
| Pneumonia pseudomonal | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Pulmonary sepsis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Respiratory tract infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Sepsis | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 4/84 (4.8%) | 4 |
| Septic shock | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Chemical peritonitis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Fall | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Investigations | ||||||
| Alanine aminotransferase increased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Aspartate aminotransferase increased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Blood creatine phosphokinase MB increased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Blood creatinine increased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Blood urea increased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Glomerular filtration rate decreased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dehydration | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Hypercalcaemia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Cholesteatoma | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Nervous system disorders | ||||||
| Depressed level of consciousness | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dizziness | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Embolic stroke | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Ischaemic stroke | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Seizure | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Syncope | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Renal failure | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Chronic obstructive pulmonary disease | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Dyspnoea | 1/43 (2.3%) | 1 | 4/84 (4.8%) | 5 | 4/84 (4.8%) | 4 |
| Haemoptysis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Interstitial lung disease | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Lung disorder | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Pleural effusion | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 3/84 (3.6%) | 3 |
| Pneumonitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Pneumothorax | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Pneumothorax spontaneous | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pulmonary embolism | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Respiratory failure | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis bullous | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Swelling face | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Vascular disorders | ||||||
| Aortic thrombosis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hypotension | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Peripheral ischaemia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Thrombosis | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Placebo + Docetaxel 75 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/43 (88.4%) | 80/84 (95.2%) | 83/84 (98.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 4/43 (9.3%) | 4 | 20/84 (23.8%) | 22 | 18/84 (21.4%) | 21 |
| Eosinophilia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Febrile neutropenia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 3/84 (3.6%) | 4 |
| Leukocytosis | 1/43 (2.3%) | 1 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Leukopenia | 2/43 (4.7%) | 3 | 2/84 (2.4%) | 2 | 3/84 (3.6%) | 3 |
| Lymphadenopathy | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Neutropenia | 10/43 (23.3%) | 12 | 9/84 (10.7%) | 26 | 17/84 (20.2%) | 19 |
| Neutrophilia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Thrombocytopenia | 1/43 (2.3%) | 1 | 2/84 (2.4%) | 2 | 2/84 (2.4%) | 3 |
| Cardiac disorders | ||||||
| Arrhythmia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Atrial fibrillation | 1/43 (2.3%) | 1 | 3/84 (3.6%) | 3 | 3/84 (3.6%) | 4 |
| Atrial flutter | 2/43 (4.7%) | 2 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Atrial tachycardia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Bundle branch block left | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Cardiac failure | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Cardiac failure congestive | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Mitral valve incompetence | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nodal rhythm | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Palpitations | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Pericarditis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Right ventricular failure | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Sinus tachycardia | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Supraventricular tachycardia | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Tachycardia | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 1/84 (1.2%) | 1 |
| Ear and labyrinth disorders | ||||||
| Deafness | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Hearing impaired | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Middle ear inflammation | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Otorrhoea | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Tinnitus | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Vertigo | 1/43 (2.3%) | 1 | 2/84 (2.4%) | 2 | 1/84 (1.2%) | 1 |
| Endocrine disorders | ||||||
| Hyperthyroidism | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Eye disorders | ||||||
| Blepharitis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Chorioretinal disorder | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Conjunctival haemorrhage | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dry eye | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 3/84 (3.6%) | 3 |
| Eye discharge | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Eye disorder | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Eye irritation | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Eye oedema | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Eye pain | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Eye swelling | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Eyelid oedema | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 5 |
| Eyelid pain | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Lacrimation increased | 2/43 (4.7%) | 2 | 2/84 (2.4%) | 2 | 7/84 (8.3%) | 7 |
| Noninfective conjunctivitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Periorbital oedema | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 3/84 (3.6%) | 4 |
| Vision blurred | 0/43 (0%) | 0 | 4/84 (4.8%) | 4 | 3/84 (3.6%) | 3 |
| Visual acuity reduced | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Visual impairment | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Abdominal distension | 0/43 (0%) | 0 | 2/84 (2.4%) | 3 | 1/84 (1.2%) | 1 |
| Abdominal pain | 3/43 (7%) | 4 | 9/84 (10.7%) | 12 | 6/84 (7.1%) | 6 |
| Abdominal pain lower | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Abdominal pain upper | 4/43 (9.3%) | 5 | 3/84 (3.6%) | 3 | 8/84 (9.5%) | 9 |
| Abdominal rigidity | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Anal haemorrhage | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Aphthous ulcer | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Breath odour | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Buccal mucosal roughening | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Chapped lips | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Cheilitis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Constipation | 5/43 (11.6%) | 5 | 16/84 (19%) | 18 | 11/84 (13.1%) | 13 |
| Dental cyst | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Diarrhoea | 12/43 (27.9%) | 21 | 41/84 (48.8%) | 78 | 37/84 (44%) | 65 |
| Diarrhoea haemorrhagic | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Diverticulum | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Dry mouth | 1/43 (2.3%) | 1 | 3/84 (3.6%) | 3 | 4/84 (4.8%) | 4 |
| Dyspepsia | 4/43 (9.3%) | 10 | 6/84 (7.1%) | 6 | 4/84 (4.8%) | 4 |
| Dysphagia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 4/84 (4.8%) | 4 |
| Eructation | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Flatulence | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Gastric ulcer | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Gastritis | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Gastrooesophageal reflux disease | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 6/84 (7.1%) | 6 |
| Glossitis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Glossodynia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Haematochezia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Haemorrhoidal haemorrhage | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Haemorrhoids | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hiatus hernia | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Hyperchlorhydria | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Hypoaesthesia oral | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Intra-abdominal haematoma | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Lip erosion | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Mouth haemorrhage | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Mouth ulceration | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 4/84 (4.8%) | 4 |
| Nausea | 10/43 (23.3%) | 22 | 25/84 (29.8%) | 33 | 23/84 (27.4%) | 36 |
| Odynophagia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Oesophagitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Oral mucosal eruption | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Oral pain | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Paraesthesia oral | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Rectal haemorrhage | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Retroperitoneal haematoma | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Steatorrhoea | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Stomatitis | 5/43 (11.6%) | 7 | 11/84 (13.1%) | 11 | 23/84 (27.4%) | 33 |
| Tooth loss | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Toothache | 1/43 (2.3%) | 2 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Vomiting | 8/43 (18.6%) | 13 | 20/84 (23.8%) | 28 | 22/84 (26.2%) | 27 |
| General disorders | ||||||
| Asthenia | 2/43 (4.7%) | 2 | 12/84 (14.3%) | 12 | 13/84 (15.5%) | 14 |
| Catheter site related reaction | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Chest discomfort | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Chest pain | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Chills | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Extravasation | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Face oedema | 0/43 (0%) | 0 | 4/84 (4.8%) | 4 | 4/84 (4.8%) | 4 |
| Fatigue | 13/43 (30.2%) | 17 | 17/84 (20.2%) | 21 | 26/84 (31%) | 32 |
| General physical health deterioration | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Generalised oedema | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 3/84 (3.6%) | 3 |
| Hyperthermia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Influenza like illness | 1/43 (2.3%) | 1 | 2/84 (2.4%) | 2 | 3/84 (3.6%) | 3 |
| Malaise | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Mucosal inflammation | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 7/84 (8.3%) | 8 |
| Non-cardiac chest pain | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Oedema | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 4/84 (4.8%) | 4 |
| Oedema peripheral | 8/43 (18.6%) | 10 | 16/84 (19%) | 22 | 28/84 (33.3%) | 38 |
| Pain | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Performance status decreased | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pyrexia | 3/43 (7%) | 5 | 11/84 (13.1%) | 15 | 11/84 (13.1%) | 20 |
| Hepatobiliary disorders | ||||||
| Hepatic steatosis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Liver disorder | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Immune system disorders | ||||||
| Drug hypersensitivity | 2/43 (4.7%) | 2 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Infections and infestations | ||||||
| Angular cheilitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Bronchitis | 2/43 (4.7%) | 2 | 2/84 (2.4%) | 2 | 6/84 (7.1%) | 6 |
| Candida infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Cellulitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Clostridium colitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Conjunctivitis | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 5/84 (6%) | 5 |
| Diverticulitis | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Ear infection | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Erysipelas | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Folliculitis | 2/43 (4.7%) | 2 | 2/84 (2.4%) | 2 | 2/84 (2.4%) | 2 |
| Fungal skin infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Gastroenteritis | 0/43 (0%) | 0 | 1/84 (1.2%) | 2 | 0/84 (0%) | 0 |
| Gastrointestinal infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Gingivitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Laryngitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Lung infection | 0/43 (0%) | 0 | 4/84 (4.8%) | 4 | 2/84 (2.4%) | 2 |
| Mastitis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nasopharyngitis | 3/43 (7%) | 3 | 4/84 (4.8%) | 5 | 1/84 (1.2%) | 1 |
| Nosocomial infection | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Ophthalmic herpes zoster | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Oral candidiasis | 3/43 (7%) | 4 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Oral fungal infection | 0/43 (0%) | 0 | 4/84 (4.8%) | 5 | 1/84 (1.2%) | 2 |
| Oral infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Paronychia | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 7/84 (8.3%) | 9 |
| Peritonitis | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Pharyngitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Pneumonia | 1/43 (2.3%) | 1 | 4/84 (4.8%) | 4 | 3/84 (3.6%) | 3 |
| Rash pustular | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 5/84 (6%) | 7 |
| Respiratory tract infection | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Respiratory tract infection bacterial | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Rhinitis | 2/43 (4.7%) | 2 | 1/84 (1.2%) | 1 | 3/84 (3.6%) | 3 |
| Septic shock | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Skin infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Staphylococcal infection | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Upper respiratory tract infection | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Urinary tract infection | 2/43 (4.7%) | 2 | 5/84 (6%) | 7 | 1/84 (1.2%) | 1 |
| Viral upper respiratory tract infection | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Vulvovaginal mycotic infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Wound infection | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Animal bite | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Bone contusion | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Contusion | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 3/84 (3.6%) | 4 |
| Fall | 1/43 (2.3%) | 1 | 2/84 (2.4%) | 2 | 1/84 (1.2%) | 1 |
| Head injury | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Laceration | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Lumbar vertebral fracture | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Overdose | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Rib fracture | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Seroma | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Skin abrasion | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Spinal compression fracture | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Sunburn | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Tendon rupture | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Wound | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 0/43 (0%) | 0 | 4/84 (4.8%) | 4 | 0/84 (0%) | 0 |
| Aspartate aminotransferase increased | 0/43 (0%) | 0 | 4/84 (4.8%) | 4 | 2/84 (2.4%) | 2 |
| Blood calcium decreased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Blood creatine phosphokinase MB increased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Blood creatine phosphokinase increased | 0/43 (0%) | 0 | 3/84 (3.6%) | 11 | 5/84 (6%) | 11 |
| Blood creatinine increased | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Blood lactate dehydrogenase increased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Blood magnesium decreased | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Blood pressure systolic increased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Blood sodium decreased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Blood triglycerides increased | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Breath sounds abnormal | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| C-reactive protein increased | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Ejection fraction decreased | 2/43 (4.7%) | 2 | 4/84 (4.8%) | 4 | 2/84 (2.4%) | 2 |
| Haemoglobin decreased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hepatic enzyme abnormal | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Hepatic enzyme increased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| International normalised ratio increased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Intraocular pressure increased | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Platelet count decreased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Prothrombin time prolonged | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Weight decreased | 4/43 (9.3%) | 4 | 3/84 (3.6%) | 3 | 6/84 (7.1%) | 6 |
| Weight increased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| White blood cell count decreased | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Abnormal loss of weight | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Central obesity | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Decreased appetite | 10/43 (23.3%) | 10 | 21/84 (25%) | 21 | 18/84 (21.4%) | 20 |
| Dehydration | 1/43 (2.3%) | 1 | 4/84 (4.8%) | 4 | 4/84 (4.8%) | 4 |
| Diabetes mellitus | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Fluid overload | 0/43 (0%) | 0 | 1/84 (1.2%) | 2 | 0/84 (0%) | 0 |
| Hypercalcaemia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hyperglycaemia | 2/43 (4.7%) | 2 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Hyperkalaemia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 3 |
| Hyperphosphataemia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Hypoalbuminaemia | 2/43 (4.7%) | 3 | 3/84 (3.6%) | 3 | 2/84 (2.4%) | 3 |
| Hypocalcaemia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hypoglycaemia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Hypokalaemia | 1/43 (2.3%) | 1 | 5/84 (6%) | 5 | 2/84 (2.4%) | 2 |
| Hypomagnesaemia | 3/43 (7%) | 3 | 3/84 (3.6%) | 4 | 2/84 (2.4%) | 3 |
| Hyponatraemia | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 4/84 (4.8%) | 4 |
| Hypophagia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hypoproteinaemia | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Vitamin K deficiency | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/43 (4.7%) | 2 | 6/84 (7.1%) | 7 | 4/84 (4.8%) | 5 |
| Back pain | 4/43 (9.3%) | 4 | 3/84 (3.6%) | 3 | 7/84 (8.3%) | 7 |
| Bone pain | 2/43 (4.7%) | 2 | 0/84 (0%) | 0 | 3/84 (3.6%) | 3 |
| Joint swelling | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Limb discomfort | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Muscle spasms | 2/43 (4.7%) | 2 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Muscular weakness | 1/43 (2.3%) | 1 | 4/84 (4.8%) | 7 | 3/84 (3.6%) | 3 |
| Musculoskeletal chest pain | 4/43 (9.3%) | 4 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Musculoskeletal discomfort | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Musculoskeletal pain | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Myalgia | 5/43 (11.6%) | 5 | 6/84 (7.1%) | 6 | 9/84 (10.7%) | 10 |
| Myopathy | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Neck pain | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 4/84 (4.8%) | 4 |
| Osteitis | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Pain in extremity | 6/43 (14%) | 7 | 4/84 (4.8%) | 5 | 2/84 (2.4%) | 2 |
| Spinal pain | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 3/84 (3.6%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Oncologic complication | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Tumour pain | 0/43 (0%) | 0 | 4/84 (4.8%) | 4 | 2/84 (2.4%) | 2 |
| Nervous system disorders | ||||||
| Ageusia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Amnesia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Ataxia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Depressed level of consciousness | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Dizziness | 7/43 (16.3%) | 7 | 5/84 (6%) | 5 | 5/84 (6%) | 5 |
| Dizziness postural | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dysaesthesia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dysarthria | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dysgeusia | 3/43 (7%) | 3 | 6/84 (7.1%) | 6 | 8/84 (9.5%) | 8 |
| Head discomfort | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Headache | 5/43 (11.6%) | 5 | 6/84 (7.1%) | 6 | 3/84 (3.6%) | 3 |
| Hemiparesis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Hepatic encephalopathy | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hypoaesthesia | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hypokinesia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Hypotonia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Lethargy | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Memory impairment | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Neuropathy peripheral | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 4/84 (4.8%) | 4 |
| Paraesthesia | 0/43 (0%) | 0 | 3/84 (3.6%) | 4 | 3/84 (3.6%) | 3 |
| Peripheral motor neuropathy | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Peripheral sensory neuropathy | 2/43 (4.7%) | 2 | 4/84 (4.8%) | 4 | 4/84 (4.8%) | 4 |
| Polyneuropathy | 1/43 (2.3%) | 1 | 4/84 (4.8%) | 4 | 3/84 (3.6%) | 4 |
| Somnolence | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Syncope | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Tremor | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Vocal cord paralysis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 0/43 (0%) | 0 | 3/84 (3.6%) | 3 | 1/84 (1.2%) | 1 |
| Delirium | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Depression | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Disorientation | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Insomnia | 2/43 (4.7%) | 2 | 4/84 (4.8%) | 5 | 3/84 (3.6%) | 3 |
| Sleep disorder | 2/43 (4.7%) | 3 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Bladder pain | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Costovertebral angle tenderness | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dysuria | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 5/84 (6%) | 6 |
| Oliguria | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pollakiuria | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Proteinuria | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Renal cyst | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Renal failure | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Renal impairment | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Renal infarct | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Renal vein thrombosis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Urinary retention | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Reproductive system and breast disorders | ||||||
| Balanoposthitis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Pelvic pain | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Vulvovaginal pruritus | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Aspiration | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Atelectasis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Bronchospasm | 2/43 (4.7%) | 2 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Chronic obstructive pulmonary disease | 1/43 (2.3%) | 1 | 3/84 (3.6%) | 3 | 0/84 (0%) | 0 |
| Cough | 8/43 (18.6%) | 8 | 7/84 (8.3%) | 7 | 10/84 (11.9%) | 10 |
| Dysphonia | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 1/84 (1.2%) | 1 |
| Dyspnoea | 4/43 (9.3%) | 4 | 12/84 (14.3%) | 12 | 14/84 (16.7%) | 15 |
| Dyspnoea exertional | 2/43 (4.7%) | 2 | 3/84 (3.6%) | 3 | 4/84 (4.8%) | 4 |
| Emphysema | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Epistaxis | 2/43 (4.7%) | 3 | 6/84 (7.1%) | 6 | 8/84 (9.5%) | 9 |
| Haemoptysis | 2/43 (4.7%) | 2 | 1/84 (1.2%) | 1 | 7/84 (8.3%) | 8 |
| Hypoxia | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Lung disorder | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Lung infiltration | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nasal discomfort | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nasal dryness | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nasal inflammation | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nasal polyps | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Oropharyngeal pain | 0/43 (0%) | 0 | 3/84 (3.6%) | 3 | 5/84 (6%) | 5 |
| Pharyngeal inflammation | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pleural effusion | 1/43 (2.3%) | 1 | 3/84 (3.6%) | 3 | 3/84 (3.6%) | 3 |
| Pleuritic pain | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pneumonitis | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Pneumothorax | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Productive cough | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Pulmonary embolism | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Pulmonary haemorrhage | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Pulmonary hypertension | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Pulmonary oedema | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Rales | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Rhinitis allergic | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Rhinorrhoea | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Sinus disorder | 1/43 (2.3%) | 2 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Sputum discoloured | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Wheezing | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Alopecia | 8/43 (18.6%) | 8 | 11/84 (13.1%) | 11 | 15/84 (17.9%) | 16 |
| Dermatitis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Dermatitis acneiform | 1/43 (2.3%) | 1 | 9/84 (10.7%) | 18 | 7/84 (8.3%) | 9 |
| Dermatitis exfoliative | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Dry skin | 2/43 (4.7%) | 2 | 9/84 (10.7%) | 10 | 16/84 (19%) | 16 |
| Eczema | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Erythema | 1/43 (2.3%) | 1 | 4/84 (4.8%) | 5 | 5/84 (6%) | 6 |
| Erythema multiforme | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Hyperhidrosis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Ingrowing nail | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Intertrigo | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Madarosis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nail discolouration | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 3/84 (3.6%) | 3 |
| Nail disorder | 2/43 (4.7%) | 2 | 3/84 (3.6%) | 3 | 1/84 (1.2%) | 1 |
| Nail growth abnormal | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nail ridging | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Night sweats | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Onychalgia | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 2 |
| Onychoclasis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Onycholysis | 1/43 (2.3%) | 1 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Onychomadesis | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Palmar-plantar erythrodysaesthesia syndrome | 1/43 (2.3%) | 1 | 0/84 (0%) | 0 | 2/84 (2.4%) | 2 |
| Petechiae | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Photosensitivity reaction | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 2/84 (2.4%) | 3 |
| Pruritus | 0/43 (0%) | 0 | 4/84 (4.8%) | 5 | 4/84 (4.8%) | 4 |
| Rash | 9/43 (20.9%) | 10 | 23/84 (27.4%) | 26 | 29/84 (34.5%) | 44 |
| Rash erythematous | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Rash generalised | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Rash macular | 0/43 (0%) | 0 | 2/84 (2.4%) | 3 | 0/84 (0%) | 0 |
| Rash maculo-papular | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 3/84 (3.6%) | 3 |
| Rash papular | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Rash pruritic | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Rosacea | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Skin exfoliation | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Skin fissures | 0/43 (0%) | 0 | 2/84 (2.4%) | 2 | 0/84 (0%) | 0 |
| Skin hyperpigmentation | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Skin ulcer | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
| Swelling face | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Urticaria | 0/43 (0%) | 0 | 1/84 (1.2%) | 2 | 0/84 (0%) | 0 |
| Xeroderma | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Vascular disorders | ||||||
| Circulatory collapse | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Embolism | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Flushing | 3/43 (7%) | 3 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Hot flush | 2/43 (4.7%) | 2 | 0/84 (0%) | 0 | 0/84 (0%) | 0 |
| Hypertension | 3/43 (7%) | 4 | 2/84 (2.4%) | 2 | 10/84 (11.9%) | 11 |
| Hypotension | 2/43 (4.7%) | 2 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Lymphoedema | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 2/84 (2.4%) | 2 |
| Orthostatic hypotension | 0/43 (0%) | 0 | 0/84 (0%) | 0 | 1/84 (1.2%) | 1 |
| Peripheral coldness | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Phlebitis | 2/43 (4.7%) | 2 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Superior vena cava syndrome | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 0/84 (0%) | 0 |
| Thrombophlebitis | 0/43 (0%) | 0 | 1/84 (1.2%) | 1 | 1/84 (1.2%) | 1 |
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 | Dr Gabriella Mariani |
|---|---|
| Organization | AstraZeneca |
| Phone | +44 (0)207 6048000 |
| ClinicalTrialTransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01750281
Other Study ID Numbers:
- D1532C00064
- 2012-003622-25
First Posted:
Dec 17, 2012
Last Update Posted:
Jul 6, 2022
Last Verified:
Jun 1, 2022