Study to Determine the Maximum Tolerated Dose of BIBW 2992 (Afatinib) When Combined With Cisplatin/Paclitaxel or Cisplatin/5-FU in Patients With Advanced Solid Tumours
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT00716417
Collaborator
(none)
47
3
2
15.7
Study Details
Study Description
Brief Summary
Study to determine the maximum tolerated dose of BIBW 2992 when combined with backbone chemotherapies consisting in cisplatin plus paclitaxel or cisplatin plus 5 FU.
The overall safety, the pharmacokinetics and the anti-tumour efficacy will also be assessed.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
47 participants
Allocation:
Non-Randomized
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib Open Label Study to Assess the Safety, Tolerability and Pharmacokinetics of Continuous Dosing With BIBW 2992 Combined With Two Different Regimens of Backbone Chemotherapy: Cisplatin Combined With 5 Fluorouracil and Cisplatin Combined With Paclitaxel in Patients With Advanced Solid Tumors.
Study Start Date
:
Jul 1, 2008
Actual Primary Completion Date
:
Jul 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A. BIBW 2992-cisplatin-paclitaxel daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-paclitaxel |
Drug: BIBW 2992
low to high dose, daily
|
| Experimental: B. BIBW 2992-cisplatin-5FU daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-5FU |
Drug: BIBW 2992
In each arm, BIBW 2992 dose will be escalated to determine MTD. Starting dose will be 20mg daily followed by 40 mg (with the option of an intermediary dose of 30 mg) then 50mg daily. Dose escalation will stop at 50 mg. No intra patient dose escalation.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) [21 days]
Number of participants with DLT in the first cycle (21 days) for the determination of the MTD.
- Maximum Tolerated Dose (MTD) for Regimen A and Regimen B [21 days]
The MTD was determined using a standard 3 +3 dose escalation cohort design. The sample size and the number of patients who receive each dose in this design depends on the frequency of DLT at each dose level in cycle 1.
Secondary Outcome Measures
- Number of Patients With Objective Response [Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days)]
Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.0. Objective response is defined as complete response (CR) and partial response (PR).
- Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss) [0.05hours (h) before administration and 1h, 2h, 2h 55 minutes (min), 4h, 4h 30min, 5h, 6h, 8h, 10h, 24h, 48h, 216h, 480h after administration]
Cmax,ss represents the maximum concentration of afatinib in plasma at steady state
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
Patients with histologically or cytologically confirmed diagnosis of non resectable and / or metastatic cancer, preferably squamous cell carcinomas of head and neck, oesophagus, lung or cervix
-
Indication for a standard treatment with either cisplatin plus paclitaxel or cisplatin plus 5 FU as judged by the investigator
-
Age 18 years or older.
-
Life expectancy of at least three (3) months.
-
Written informed consent that is consistent with ICH-GCP guidelines.
-
Eastern Cooperative Oncology Group (ECOG) performance score less or equal 2.
-
Patients must have recovered from any therapy-related toxicity from previous chemo-, hormone-, immuno-, or radiotherapies.
-
Patients recovered from previous surgery.
Exclusion criteria:
-
Active infectious disease.
-
Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea.
-
Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
-
Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks and no requirement for steroids or anti-epileptic therapy.
-
Cardiac left ventricular function with resting ejection fraction less than 50%
-
Absolute neutrophil count (ANC) less than 1500 / mm3.
-
Platelets count less than 100 000/mm3.
-
Bilirubin more than 1.5 x upper limit of institutional norm.
-
Aspartate amino transferase (AST) or alanine amino transferase (ALT) more than 3 x upper limit of institutional norm.
-
Serum creatinine more than 1.5 x upper limit of institutional norm.
-
Women and men sexually active and unwilling to use a medically acceptable method of contraception.
-
Pregnancy or breast-feeding.
-
Treatment with other investigational drugs; chemotherapy, immunotherapy, or radiotherapy or participation in another clinical study with anti-cancer therapy within the past 4 weeks before start of therapy or concomitantly with this study.
-
Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (2 weeks for trastuzumab).
-
Patients unable to comply with the protocol.
-
Active alcohol or drug abuse.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1200.37.3202 Boehringer Ingelheim Investigational Site | Bruxelles | Belgium | ||
| 2 | 1200.37.3201 Boehringer Ingelheim Investigational Site | Edegem | Belgium | ||
| 3 | 1200.37.3203 Boehringer Ingelheim Investigational Site | Gent | Belgium |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00716417
Other Study ID Numbers:
- 1200.37
- 2008-002613-43
First Posted:
Jul 16, 2008
Last Update Posted:
Jun 9, 2014
Last Verified:
Aug 1, 2013
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. |
| Period Title: Overall Study | ||||||||||
| STARTED | 3 | 6 | 5 | 11 | 1 | 3 | 7 | 3 | 5 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 6 | 5 | 11 | 1 | 3 | 7 | 3 | 5 | 3 |
Baseline Characteristics
| Arm/Group Title | Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Total of all reporting groups |
| Overall Participants | 3 | 6 | 5 | 11 | 1 | 3 | 7 | 3 | 5 | 3 | 47 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||
| Mean (Standard Deviation) [years] |
56.7
(14.0)
|
61.8
(15.6)
|
61.8
(5.9)
|
58.1
(7.8)
|
54.0
(NA)
|
52.7
(9.7)
|
53.1
(16.1)
|
65.0
(8.5)
|
59.2
(14.4)
|
63.7
(9.3)
|
58.58
(11.3)
|
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
3
100%
|
3
50%
|
2
40%
|
3
27.3%
|
0
0%
|
0
0%
|
2
28.6%
|
2
66.7%
|
3
60%
|
1
33.3%
|
19
40.4%
|
| Male |
0
0%
|
3
50%
|
3
60%
|
8
72.7%
|
1
100%
|
3
100%
|
5
71.4%
|
1
33.3%
|
2
40%
|
2
66.7%
|
28
59.6%
|
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) |
|---|---|
| Description | Number of participants with DLT in the first cycle (21 days) for the determination of the MTD. |
| Time Frame | 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated Set (TS) - TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. |
| Arm/Group Title | Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. |
| Measure Participants | 3 | 6 | 5 | 11 | 1 | 3 | 7 | 3 | 5 | 3 |
| Number [Participants] |
0
0%
|
0
0%
|
2
40%
|
2
18.2%
|
1
100%
|
0
0%
|
0
0%
|
2
66.7%
|
0
0%
|
2
66.7%
|
| Title | Maximum Tolerated Dose (MTD) for Regimen A and Regimen B |
|---|---|
| Description | The MTD was determined using a standard 3 +3 dose escalation cohort design. The sample size and the number of patients who receive each dose in this design depends on the frequency of DLT at each dose level in cycle 1. |
| Time Frame | 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated Set (TS) - TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. |
| Arm/Group Title | Pac + Cis + Afatinib (Regimen A) | 5FU + Cis + Afatinib (Regimen B) |
|---|---|---|
| Arm/Group Description | Patients received continous daily dosing with Afatinib film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel and Cisplatin on day 1 of each cycle in 5 dose levels as outlined in first primary endpoint. | Patients received continous daily dosing with Afatinib film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil and Cisplatin on day 1 of each cycle in 5 dose levels as outlined in first primary endpoint. |
| Measure Participants | 26 | 21 |
| Maximum tolerated dose - Afatinib |
20
|
30
|
| Maximum tolerated dose - Cisplatin |
75
|
100
|
| Maximum tolerated dose - Pac (A) or 5-FU (B) |
175
|
750
|
| Title | Number of Patients With Objective Response |
|---|---|
| Description | Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.0. Objective response is defined as complete response (CR) and partial response (PR). |
| Time Frame | Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated Set (TS) - TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. |
| Arm/Group Title | Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. |
| Measure Participants | 3 | 6 | 5 | 11 | 1 | 3 | 7 | 3 | 5 | 3 |
| Number [Participants] |
1
33.3%
|
0
0%
|
0
0%
|
4
36.4%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss) |
|---|---|
| Description | Cmax,ss represents the maximum concentration of afatinib in plasma at steady state |
| Time Frame | 0.05hours (h) before administration and 1h, 2h, 2h 55 minutes (min), 4h, 4h 30min, 5h, 6h, 8h, 10h, 24h, 48h, 216h, 480h after administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis set includes all patients who took at least one dose of trial medication and provided at least one blood sample following drug administration. Values were excluded from descriptive statistics when a comparison with plasma concentrations in the same treatment group was impossible. |
| Arm/Group Title | Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. |
| Measure Participants | 3 | 4 | 2 | 4 | 0 | 3 | 6 | 1 | 3 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
22.1
(22.5)
|
18.0
(24.9)
|
17.7
(13.2)
|
32.1
(79.2)
|
48.9
(26.0)
|
57.0
(41.1)
|
32.7
(NA)
|
13.4
(28.9)
|
17.3
(NA)
|
Adverse Events
| Time Frame | First administration of trial medication until 28 days after last administration of trial medication | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||
| Arm/Group Title | Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 | ||||||||||
| Arm/Group Description | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 50mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 75mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m^2 and Cisplatin 100mg/m^2 on day 1 of each cycle. Treatment until disease progression or toxicity. | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 5/6 (83.3%) | 4/5 (80%) | 7/11 (63.6%) | 1/1 (100%) | 2/3 (66.7%) | 6/7 (85.7%) | 3/3 (100%) | 1/5 (20%) | 3/3 (100%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anaemia | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Febrile neutropenia | 0/3 (0%) | 2/6 (33.3%) | 0/5 (0%) | 0/11 (0%) | 1/1 (100%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Neutropenia | 0/3 (0%) | 2/6 (33.3%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Thrombocytopenia | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Atrial fibrillation | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal pain | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Diarrhoea | 0/3 (0%) | 2/6 (33.3%) | 3/5 (60%) | 4/11 (36.4%) | 0/1 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 3/3 (100%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Duodenal obstruction | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nausea | 0/3 (0%) | 1/6 (16.7%) | 2/5 (40%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 2/7 (28.6%) | 2/3 (66.7%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Stomatitis | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Vomiting | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 3/7 (42.9%) | 1/3 (33.3%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Asthenia | 0/3 (0%) | 0/6 (0%) | 2/5 (40%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Fatigue | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| General physical health deterioration | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Mucosal inflammation | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Pyrexia | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||
| Hepatic failure | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Brain abscess | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Erysipelas | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Sepsis | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Septic shock | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 1/1 (100%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Investigations | ||||||||||||||||||||
| Blood creatinine increased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Weight decreased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Decreased appetite | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 2/3 (66.7%) | 2/7 (28.6%) | 2/3 (66.7%) | 1/5 (20%) | 3/3 (100%) | ||||||||||
| Dehydration | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Food intolerance | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hypokalaemia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hyponatraemia | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Bone pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Muscular weakness | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Malignant neoplasm progression | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Renal cell carcinoma | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 1/1 (100%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Balance disorder | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Headache | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Psychiatric disorders | ||||||||||||||||||||
| Confusional state | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Renal failure | 1/3 (33.3%) | 0/6 (0%) | 1/5 (20%) | 3/11 (27.3%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Acute pulmonary oedema | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Acute respiratory distress syndrome | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Cough | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Dyspnoea | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 0/11 (0%) | 1/1 (100%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Dyspnoea exertional | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Pulmonary embolism | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Rash | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Orthostatic hypotension | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| Pac175 + Cis50 + Afatinib20 | Pac175 + Cis75 + Afatinib20 | Pac175 + Cis75 + Afatinib30 | Pac175 + Cis75 + Afatinib40 | Pac175 + Cis75 + Afatinib50 | Cis75 + 5FU750 + Afatinib20 | Cis75 + 5FU750 + Afatinib30 | Cis75 + 5FU750 + Afatinib40 | Cis100 + 5FU750 + Afatinib30 | Cis100 + 5FU1000 + Afatinib30 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 6/6 (100%) | 5/5 (100%) | 11/11 (100%) | 1/1 (100%) | 3/3 (100%) | 7/7 (100%) | 3/3 (100%) | 5/5 (100%) | 3/3 (100%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anaemia | 2/3 (66.7%) | 4/6 (66.7%) | 1/5 (20%) | 6/11 (54.5%) | 0/1 (0%) | 1/3 (33.3%) | 3/7 (42.9%) | 2/3 (66.7%) | 2/5 (40%) | 2/3 (66.7%) | ||||||||||
| Coagulopathy | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Febrile neutropenia | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Leukopenia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Neutropenia | 1/3 (33.3%) | 3/6 (50%) | 0/5 (0%) | 6/11 (54.5%) | 0/1 (0%) | 2/3 (66.7%) | 1/7 (14.3%) | 1/3 (33.3%) | 2/5 (40%) | 2/3 (66.7%) | ||||||||||
| Thrombocytopenia | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 2/7 (28.6%) | 1/3 (33.3%) | 1/5 (20%) | 2/3 (66.7%) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Atrial fibrillation | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Bundle branch block right | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Conduction disorder | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Tachycardia | 0/3 (0%) | 2/6 (33.3%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 2/7 (28.6%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||
| Deafness | 1/3 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Deafness unilateral | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Ear pain | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Tinnitus | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 2/3 (66.7%) | 0/7 (0%) | 0/3 (0%) | 2/5 (40%) | 0/3 (0%) | ||||||||||
| Vertigo | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Eye disorders | ||||||||||||||||||||
| Cataract | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Conjunctivitis | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Dry eye | 1/3 (33.3%) | 2/6 (33.3%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Eye haemorrhage | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Eye irritation | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Eye swelling | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Visual acuity reduced | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal discomfort | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Abdominal pain | 1/3 (33.3%) | 0/6 (0%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Abdominal pain upper | 1/3 (33.3%) | 0/6 (0%) | 2/5 (40%) | 4/11 (36.4%) | 0/1 (0%) | 2/3 (66.7%) | 1/7 (14.3%) | 1/3 (33.3%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Anorectal discomfort | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Aphthous stomatitis | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Constipation | 1/3 (33.3%) | 2/6 (33.3%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 2/3 (66.7%) | 2/7 (28.6%) | 1/3 (33.3%) | 3/5 (60%) | 1/3 (33.3%) | ||||||||||
| Diarrhoea | 3/3 (100%) | 2/6 (33.3%) | 2/5 (40%) | 6/11 (54.5%) | 1/1 (100%) | 2/3 (66.7%) | 5/7 (71.4%) | 0/3 (0%) | 3/5 (60%) | 3/3 (100%) | ||||||||||
| Dry mouth | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Dyspepsia | 1/3 (33.3%) | 1/6 (16.7%) | 2/5 (40%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 2/7 (28.6%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Dysphagia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Gastric ulcer | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Gastrointestinal obstruction | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Gastrooesophageal reflux disease | 2/3 (66.7%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Haemorrhoids | 1/3 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Inguinal hernia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Lip disorder | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Lip dry | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nausea | 2/3 (66.7%) | 4/6 (66.7%) | 3/5 (60%) | 8/11 (72.7%) | 0/1 (0%) | 2/3 (66.7%) | 5/7 (71.4%) | 1/3 (33.3%) | 2/5 (40%) | 3/3 (100%) | ||||||||||
| Oral pain | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Proctalgia | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Stomatitis | 1/3 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 1/3 (33.3%) | 2/5 (40%) | 1/3 (33.3%) | ||||||||||
| Toothache | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Vomiting | 2/3 (66.7%) | 1/6 (16.7%) | 4/5 (80%) | 2/11 (18.2%) | 1/1 (100%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 3/5 (60%) | 2/3 (66.7%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Asthenia | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Catheter site pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Chest pain | 0/3 (0%) | 2/6 (33.3%) | 0/5 (0%) | 3/11 (27.3%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Fatigue | 2/3 (66.7%) | 2/6 (33.3%) | 0/5 (0%) | 10/11 (90.9%) | 0/1 (0%) | 1/3 (33.3%) | 6/7 (85.7%) | 2/3 (66.7%) | 3/5 (60%) | 2/3 (66.7%) | ||||||||||
| Feeling cold | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Influenza like illness | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Localised oedema | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Mucosal inflammation | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Oedema | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Oedema peripheral | 1/3 (33.3%) | 2/6 (33.3%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 3/5 (60%) | 0/3 (0%) | ||||||||||
| Pain | 1/3 (33.3%) | 0/6 (0%) | 2/5 (40%) | 1/11 (9.1%) | 0/1 (0%) | 1/3 (33.3%) | 2/7 (28.6%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Pyrexia | 2/3 (66.7%) | 2/6 (33.3%) | 2/5 (40%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 2/3 (66.7%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||
| Hepatic pain | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Immune system disorders | ||||||||||||||||||||
| Drug hypersensitivity | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Bronchitis | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Cystitis | 1/3 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Eye infection | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Folliculitis | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Fungal infection | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Furuncle | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Genital infection fungal | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Herpes zoster | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Infection | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Klebsiella infection | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nail infection | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nasopharyngitis | 1/3 (33.3%) | 2/6 (33.3%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 2/3 (66.7%) | ||||||||||
| Omphalitis | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Oral fungal infection | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Paronychia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Rash pustular | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Rhinitis | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Skin infection | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Urinary tract infection | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Urinary tract infection enterococcal | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Urinary tract infection fungal | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Vaginal infection | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Medication error | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Wound | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Investigations | ||||||||||||||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Aspartate aminotransferase increased | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Blood alkaline phosphatase | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Blood creatinine decreased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Blood creatinine increased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 1/1 (100%) | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 2/5 (40%) | 2/3 (66.7%) | ||||||||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Blood phosphorus decreased | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Blood urea increased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| C-reactive protein increased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Ejection fraction decreased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Electrocardiogram ST segment depression | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Electrocardiogram ST segment elevation | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Gamma-glutamyltransferase increased | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Glomerular filtration rate decreased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Platelet count decreased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Weight decreased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 3/11 (27.3%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| White blood cell count increased | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Decreased appetite | 3/3 (100%) | 3/6 (50%) | 2/5 (40%) | 4/11 (36.4%) | 0/1 (0%) | 0/3 (0%) | 2/7 (28.6%) | 1/3 (33.3%) | 3/5 (60%) | 0/3 (0%) | ||||||||||
| Dehydration | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Electrolyte imbalance | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Fluid imbalance | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Fluid retention | 0/3 (0%) | 2/6 (33.3%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Hypercalcaemia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Hyperglycaemia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Hyperkalaemia | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hypermagnesaemia | 0/3 (0%) | 0/6 (0%) | 2/5 (40%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hypocalcaemia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hypokalaemia | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 3/11 (27.3%) | 0/1 (0%) | 1/3 (33.3%) | 3/7 (42.9%) | 3/3 (100%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hypomagnesaemia | 1/3 (33.3%) | 2/6 (33.3%) | 2/5 (40%) | 6/11 (54.5%) | 0/1 (0%) | 0/3 (0%) | 2/7 (28.6%) | 0/3 (0%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Hyponatraemia | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 1/1 (100%) | 0/3 (0%) | 0/7 (0%) | 2/3 (66.7%) | 0/5 (0%) | 2/3 (66.7%) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Arthralgia | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Back pain | 2/3 (66.7%) | 2/6 (33.3%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Bone pain | 0/3 (0%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Hypercreatinaemia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Muscle spasms | 1/3 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 2/3 (66.7%) | ||||||||||
| Muscular weakness | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Musculoskeletal chest pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Musculoskeletal pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 3/11 (27.3%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Musculoskeletal stiffness | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Myalgia | 1/3 (33.3%) | 1/6 (16.7%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Neck pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Pain in extremity | 0/3 (0%) | 1/6 (16.7%) | 2/5 (40%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Pain in jaw | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Infected neoplasm | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Tumour pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Ageusia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Dizziness | 2/3 (66.7%) | 3/6 (50%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 2/5 (40%) | 2/3 (66.7%) | ||||||||||
| Dysgeusia | 0/3 (0%) | 2/6 (33.3%) | 2/5 (40%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Headache | 0/3 (0%) | 2/6 (33.3%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Hyperaesthesia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Neuropathy peripheral | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Neurotoxicity | 0/3 (0%) | 2/6 (33.3%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Paraesthesia | 1/3 (33.3%) | 0/6 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Peripheral motor neuropathy | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Peripheral sensory neuropathy | 2/3 (66.7%) | 2/6 (33.3%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Sensory loss | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Psychiatric disorders | ||||||||||||||||||||
| Agitation | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Anxiety | 1/3 (33.3%) | 2/6 (33.3%) | 2/5 (40%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Confusional state | 0/3 (0%) | 2/6 (33.3%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Depressed mood | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Depression | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Insomnia | 0/3 (0%) | 0/6 (0%) | 2/5 (40%) | 4/11 (36.4%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Self esteem inflated | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Dysuria | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Haematuria | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Nocturia | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Oliguria | 1/3 (33.3%) | 0/6 (0%) | 1/5 (20%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Pollakiuria | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Renal failure | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Stress urinary incontinence | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||
| Breast pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Pelvic pain | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Testicular swelling | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Vulvovaginal dryness | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Cough | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 2/5 (40%) | 1/3 (33.3%) | ||||||||||
| Dysphonia | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Dyspnoea | 0/3 (0%) | 1/6 (16.7%) | 2/5 (40%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 3/7 (42.9%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Dyspnoea exertional | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Epistaxis | 1/3 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 3/11 (27.3%) | 0/1 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 1/3 (33.3%) | 2/5 (40%) | 1/3 (33.3%) | ||||||||||
| Hiccups | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nasal discomfort | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nasal dryness | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Oropharyngeal pain | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Pharyngeal oedema | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Productive cough | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 2/3 (66.7%) | ||||||||||
| Pulmonary embolism | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Rhinorrhoea | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Sputum increased | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Acne | 0/3 (0%) | 1/6 (16.7%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 1/3 (33.3%) | 2/7 (28.6%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Alopecia | 1/3 (33.3%) | 2/6 (33.3%) | 2/5 (40%) | 4/11 (36.4%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 2/5 (40%) | 1/3 (33.3%) | ||||||||||
| Dermatitis | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Dermatitis acneiform | 2/3 (66.7%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Dry skin | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Eczema asteatotic | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Erythema | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Nail disorder | 1/3 (33.3%) | 0/6 (0%) | 1/5 (20%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Nail pitting | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Night sweats | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Pruritus | 1/3 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Pruritus generalised | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Rash | 2/3 (66.7%) | 2/6 (33.3%) | 0/5 (0%) | 5/11 (45.5%) | 0/1 (0%) | 2/3 (66.7%) | 1/7 (14.3%) | 1/3 (33.3%) | 1/5 (20%) | 1/3 (33.3%) | ||||||||||
| Skin fissures | 1/3 (33.3%) | 1/6 (16.7%) | 1/5 (20%) | 2/11 (18.2%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 1/3 (33.3%) | ||||||||||
| Skin fragility | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Skin lesion | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Flushing | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 1/5 (20%) | 0/3 (0%) | ||||||||||
| Hypertension | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 2/5 (40%) | 1/3 (33.3%) | ||||||||||
| Hypotension | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 1/11 (9.1%) | 0/1 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Orthostatic hypotension | 0/3 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
| Venous thrombosis limb | 1/3 (33.3%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/1 (0%) | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/5 (0%) | 0/3 (0%) | ||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication
Results Point of Contact
| Name/Title | Boehringer Ingelheim Call Center |
|---|---|
| Organization | Boehringer Ingelheim Pharmaceuticals |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00716417
Other Study ID Numbers:
- 1200.37
- 2008-002613-43
First Posted:
Jul 16, 2008
Last Update Posted:
Jun 9, 2014
Last Verified:
Aug 1, 2013