Safety of AMG 706 Plus Panitumumab Plus Gemcitabine-Cisplatin in the Treatment of Patients With Advanced Cancer
Sponsor
Amgen (Industry)
Overall Status
Terminated
CT.gov ID
NCT00101907
Collaborator
(none)
41
6
40
Study Details
Study Description
Brief Summary
The purpose of this study is to characterize the safety and tolerability of AMG 706 plus panitumumab when administered with gemcitabine and cisplatin chemotherapy. This is a Phase 1b clinical study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
41 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Dose-Finding Study to Evaluate the Safety of AMG 706 Plus Panitumumab Plus Gemcitabine-Cisplatin in the Treatment of Subjects With Advanced Cancer
Study Start Date
:
Dec 1, 2004
Actual Primary Completion Date
:
Jun 1, 2007
Actual Study Completion Date
:
Apr 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Panitumumab + Gem/Cis Panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle. |
Biological: Panitumumab
Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.
Other Names:
Drug: Gemcitabine
Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.
Other Names:
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
|
| Experimental: 50 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle. |
Drug: AMG 706
AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1.
Biological: Panitumumab
Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.
Other Names:
Drug: Gemcitabine
Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.
Other Names:
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
|
| Experimental: 75 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle. |
Drug: AMG 706
AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1.
Biological: Panitumumab
Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.
Other Names:
Drug: Gemcitabine
Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.
Other Names:
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
|
| Experimental: 100 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle. |
Drug: AMG 706
AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1.
Biological: Panitumumab
Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.
Other Names:
Drug: Gemcitabine
Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.
Other Names:
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
|
| Experimental: 125 mg QD AMG 706 + panitumumab + Gem/Cis AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle. |
Drug: AMG 706
AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1.
Biological: Panitumumab
Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.
Other Names:
Drug: Gemcitabine
Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.
Other Names:
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
|
| Experimental: 75 mg BID AMG 706 + panitumumab + Gem/Cis AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle. |
Drug: AMG 706
AMG 706 will be provided as 25-mg and 100-mg tablets and will be continuously self-administered orally once or twice daily based on cohort assignment starting on day 1 of Cycle 1.
Biological: Panitumumab
Panitumumab will be administered by intravenous (IV) infusion at a dose of 9 mg/kg on Day 1 of each 3-week cycle.
Other Names:
Drug: Gemcitabine
Gemcitabine will be administered intravenously on Day 1 and Day 8 of each 21-day cycle at a dose of 1250 mg/m^2.
Other Names:
Drug: Cisplatin
Cisplatin will be administered intravenously on Day 1 of each 3-week cycle at a dose of 75 mg/m^2.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Participant Incidence of Adverse Events [From the first dose of any study treatment until 30 days after the last dose of study treatment, up to a maximum of 509 days.]
The number of participants who experienced at least one treatment-emergent adverse event. Additional details regarding specfic adverse events are provided in the Adverse Event section of this posting.
Secondary Outcome Measures
- Number of Participants With an Objective Tumor Response [From enrollment until date of last follow-up visit. The median follow-up time was 24 weeks, with a range of 3 to 73 weeks.]
The number of participants with a confirmed objective tumor response, defined as a complete response (CR) or partial response (PR) throughout based on modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Any CR or PR was to be confirmed 4 to 6 weeks after the initial CR or PR.
- Tmax [Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.]
Time after dosing when maximum plasma concentration was observed for AMG 706
- Cmax [Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.]
The maximum observed plasma concentration after AMG 706 dosing
- AUC0-24 [Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.]
Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC0-24) with AMG 706. AUC0-24 was estimated using the linear/log trapezoidal method. For the BID cohort, AUC0 24 was estimated as 2 times the AUC from time 0 to 12 hours post the first daily dose (AUC0-12) using the linear/log trapezoidal method.
- AUC0-inf [Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose.]
Area under the concentration-time curve from time 0 to infinite time (AUC0-inf) postdose with AMG 706. AUC0-inf was estimated using the linear/log trapezoidal method. AUC0-inf was not calculated for the BID cohort.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
For complete inclusion and exclusion, please refer to the investigator.
Inclusion Criteria:
-
Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form
-
Subjects with advanced cancer in whom the gemcitabine and cisplatin chemotherapy regimen is clinically indicated
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Adequate hematological function
-
Adequate renal function
-
Adequate hepatic function
-
Life expectancy of greater than or equal to 3 months as documented by the investigator
Exclusion Criteria:
-
More than 1 prior chemotherapy regimen
-
History of venous thrombosis
-
Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, or unstable angina within 1 year before study enrollment
-
History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan
-
Average systolic blood pressure of greater than 145 mm Hg or average diastolic blood pressure of greater than 85 mm Hg
-
Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions
-
Prior AMG 706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab [Erbitux®] or EMD 72000)
-
Systemic chemotherapy within 28 days before study enrollment
-
Major surgery within 28 days or minor surgery within 14 days of study enrollment
-
Central nervous system metastases (Exception: subjects with treated asymptomatic central nervous system metastases, those who have been clinically stable in the judgment of the investigator and off steroids for at least 30 days before the study enrollment are eligible)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Burris H, Stephenson J, Otterson GA, Stein M, McGreivy J, Sun YN, Ingram M, Ye Y, Schwartzberg LS. Safety and pharmacokinetics of motesanib in combination with panitumumab and gemcitabine-Cisplatin in patients with advanced cancer. J Oncol. 2011;2011:853931. doi: 10.1155/2011/853931. Epub 2011 Apr 14.
- TBD.Safety and pharmacokinetics (PK) of AMG 706 in combination with panitumumab and gemcitabine-cisplatin in patients (pts) with advanced cancer.Journal-004521;
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00101907
Other Study ID Numbers:
- 20040206
First Posted:
Jan 19, 2005
Last Update Posted:
Mar 20, 2014
Last Verified:
Feb 1, 2014
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled from 2 December 2004 through 7 March 2007. This study was designed with two parts. However, Part 2 was not conducted due to safety issues found in Part 1. Thus Part 1 is referenced as the overall study here. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis |
|---|---|---|---|---|---|---|
| Arm/Group Description | Panitumumab 9 mg/kg intravenously (IV) on Day 1 + gemcitabine (gem) 1250 mg/m^2 IV on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 IV on Day 1 of each 3-week cycle. | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. |
| Period Title: Overall Study | ||||||
| STARTED | 8 | 8 | 6 | 6 | 11 | 2 |
| COMPLETED | 6 | 7 | 5 | 5 | 6 | 2 |
| NOT COMPLETED | 2 | 1 | 1 | 1 | 5 | 0 |
Baseline Characteristics
| Arm/Group Title | Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Panitumumab 9 mg/kg on Day 1 + gemcitabine (gem) 1250 mg/m^2 on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | Total of all reporting groups |
| Overall Participants | 8 | 8 | 6 | 6 | 11 | 2 | 41 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
55.5
(12.4)
|
60.4
(13.8)
|
56.0
(13.3)
|
51.5
(13.5)
|
61.1
(8.3)
|
65.0
(17.0)
|
57.9
(12.0)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
4
50%
|
3
37.5%
|
2
33.3%
|
4
66.7%
|
5
45.5%
|
0
0%
|
18
43.9%
|
| Male |
4
50%
|
5
62.5%
|
4
66.7%
|
2
33.3%
|
6
54.5%
|
2
100%
|
23
56.1%
|
| Race/Ethnicity, Customized (Number) [Number] | |||||||
| Black or African American |
1
12.5%
|
1
12.5%
|
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
4
9.8%
|
| Hispanic or Latino |
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| White or Caucasian |
6
75%
|
7
87.5%
|
4
66.7%
|
6
100%
|
11
100%
|
2
100%
|
36
87.8%
|
Outcome Measures
| Title | Number of Participants With an Objective Tumor Response |
|---|---|
| Description | The number of participants with a confirmed objective tumor response, defined as a complete response (CR) or partial response (PR) throughout based on modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Any CR or PR was to be confirmed 4 to 6 weeks after the initial CR or PR. |
| Time Frame | From enrollment until date of last follow-up visit. The median follow-up time was 24 weeks, with a range of 3 to 73 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Analysis Set, defined as defined as patients who received at least 1 dose of AMG 706 for AMG 706 treatment groups and patients who received at least 1 dose of panitumumab for the panitumumab-only treatment group. |
| Arm/Group Title | Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis |
|---|---|---|---|---|---|---|
| Arm/Group Description | Panitumumab 9 mg/kg intravenously (IV) on Day 1 + gemcitabine (gem) 1250 mg/m^2 IV on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 IV on Day 1 of each 3-week cycle. | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. |
| Measure Participants | 8 | 8 | 6 | 6 | 11 | 2 |
| Number [participants] |
2
25%
|
0
0%
|
1
16.7%
|
4
66.7%
|
2
18.2%
|
1
50%
|
| Title | Tmax |
|---|---|
| Description | Time after dosing when maximum plasma concentration was observed for AMG 706 |
| Time Frame | Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic (PK) Analysis Set consists of patients who had dosing and PK sampling times recorded on the day of PK sample collection and no significant protocol deviations that impacted the quality of the PK data (for example, sample processing errors and/or inaccurate dosing on the day of the PK sampling). |
| Arm/Group Title | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis |
|---|---|---|---|---|---|
| Arm/Group Description | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. |
| Measure Participants | 8 | 6 | 4 | 11 | 2 |
| Median (Full Range) [hours] |
1.00
|
1.00
|
1.38
|
1.00
|
1.00
|
| Title | Cmax |
|---|---|
| Description | The maximum observed plasma concentration after AMG 706 dosing |
| Time Frame | Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. |
| Arm/Group Title | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis |
|---|---|---|---|---|---|
| Arm/Group Description | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. |
| Measure Participants | 8 | 6 | 4 | 11 | 2 |
| Mean (Standard Deviation) [ng/mL] |
152
(78)
|
186
(92)
|
278
(90)
|
458
(208)
|
268
(NA)
|
| Title | AUC0-24 |
|---|---|
| Description | Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC0-24) with AMG 706. AUC0-24 was estimated using the linear/log trapezoidal method. For the BID cohort, AUC0 24 was estimated as 2 times the AUC from time 0 to 12 hours post the first daily dose (AUC0-12) using the linear/log trapezoidal method. |
| Time Frame | Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis set; Patients with elevated AMG 706 concentrations at 24 hours were excluded from the AUC summary statistics calculations. |
| Arm/Group Title | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis |
|---|---|---|---|---|---|
| Arm/Group Description | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. |
| Measure Participants | 7 | 4 | 2 | 11 | 2 |
| Mean (Standard Deviation) [μg*hr/mL] |
1.03
(0.50)
|
1.31
(0.51)
|
2.38
(NA)
|
2.82
(1.02)
|
2.54
(NA)
|
| Title | AUC0-inf |
|---|---|
| Description | Area under the concentration-time curve from time 0 to infinite time (AUC0-inf) postdose with AMG 706. AUC0-inf was estimated using the linear/log trapezoidal method. AUC0-inf was not calculated for the BID cohort. |
| Time Frame | Day 1, pre-dose and at 1, 3, 6,12 (BID cohort only) and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Patients with elevated AMG 706 concentrations at 24 hours were excluded from the AUC summary statistics calculations. |
| Arm/Group Title | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis |
|---|---|---|---|---|---|
| Arm/Group Description | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. |
| Measure Participants | 7 | 3 | 2 | 9 | 0 |
| Mean (Standard Deviation) [μg*hr/mL] |
1.12
(0.52)
|
1.64
(0.48)
|
2.59
(NA)
|
3.05
(1.34)
|
| Title | Participant Incidence of Adverse Events |
|---|---|
| Description | The number of participants who experienced at least one treatment-emergent adverse event. Additional details regarding specfic adverse events are provided in the Adverse Event section of this posting. |
| Time Frame | From the first dose of any study treatment until 30 days after the last dose of study treatment, up to a maximum of 509 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set, composed of all participants in the AMG 706 treatment groups who received at least one dose of AMG 706 and all participants in the panitumumab-only treatment group who received at least one dose of panitumumab. |
| Arm/Group Title | Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg BID AMG 706 + Panitumumab + Gem/Cis |
|---|---|---|---|---|---|---|
| Arm/Group Description | Panitumumab 9 mg/kg intravenously (IV) on Day 1 + gemcitabine (gem) 1250 mg/m^2 IV on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 IV on Day 1 of each 3-week cycle. | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg intravenously on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. |
| Measure Participants | 8 | 8 | 6 | 6 | 11 | 2 |
| Number [Participants] |
8
100%
|
8
100%
|
6
100%
|
6
100%
|
11
100%
|
2
100%
|
Adverse Events
| Time Frame | From the first dose of any study treatment until 30 days after the last dose of study treatment, up to a maximum of 509 days. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. | |||||||||||
| Arm/Group Title | Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/CisEdit | 75 mg BID AMG 706 + Panitumumab + Gem/CisEdit | ||||||
| Arm/Group Description | Panitumumab 9 mg/kg intravenously (IV) on Day 1 + gemcitabine (gem) 1250 mg/m^2 IV on Day 1 and Day 8, and cisplatin (cis) 75 mg/m^2 IV on Day 1 of each 3-week cycle. | AMG 706 50 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 100 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 125 mg administered orally once daily (QD) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | AMG 706 75 mg administered orally twice daily (BID) + panitumumab 9 mg/kg on Day 1 + gemcitabine 1250 mg/m^2 on Day 1 and Day 8, and cisplatin 75 mg/m^2 on Day 1 of each 3-week cycle. | ||||||
All Cause Mortality |
||||||||||||
| Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/CisEdit | 75 mg BID AMG 706 + Panitumumab + Gem/CisEdit | |||||||
| 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) | ||||||
Serious Adverse Events |
||||||||||||
| Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/CisEdit | 75 mg BID AMG 706 + Panitumumab + Gem/CisEdit | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/8 (25%) | 4/8 (50%) | 3/6 (50%) | 4/6 (66.7%) | 9/11 (81.8%) | 1/2 (50%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Neutropenia | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Thrombocytopenia | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Cardiac disorders | ||||||||||||
| Angina pectoris | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Atrial fibrillation | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Cardiac failure congestive | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Cardiomyopathy | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Endocrine disorders | ||||||||||||
| Hypothyroidism | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Anal fistula | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Diarrhoea | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Nausea | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Oesophageal perforation | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Vomiting | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| General disorders | ||||||||||||
| Asthenia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Fatigue | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Pyrexia | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Sudden death | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Cholecystitis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Cholelithiasis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hepatic failure | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Catheter related infection | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Diverticulitis | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Pneumonia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Sepsis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Narcotic intoxication | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Overdose | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Dehydration | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Fluid retention | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hypercalcaemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hyperkalaemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hyponatraemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Transitional cell carcinoma | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Cerebrovascular accident | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Headache | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Syncope | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Psychiatric disorders | ||||||||||||
| Confusional state | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Pneumothorax | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Pulmonary embolism | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 1/6 (16.7%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Respiratory failure | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Arterial thrombosis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 1/2 (50%) | ||||||
| Deep vein thrombosis | 0/8 (0%) | 2/8 (25%) | 0/6 (0%) | 1/6 (16.7%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| Panitumumab + Gem/Cis | 50 mg QD AMG 706 + Panitumumab + Gem/Cis | 75 mg QD AMG 706 + Panitumumab + Gem/Cis | 100 mg QD AMG 706 + Panitumumab + Gem/Cis | 125 mg QD AMG 706 + Panitumumab + Gem/CisEdit | 75 mg BID AMG 706 + Panitumumab + Gem/CisEdit | |||||||
| 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 | 8/8 (100%) | 8/8 (100%) | 6/6 (100%) | 6/6 (100%) | 11/11 (100%) | 2/2 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 6/8 (75%) | 5/8 (62.5%) | 2/6 (33.3%) | 5/6 (83.3%) | 4/11 (36.4%) | 1/2 (50%) | ||||||
| Haemorrhagic diathesis | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hypocoagulable state | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Leukopenia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Lymphadenitis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Neutropenia | 4/8 (50%) | 5/8 (62.5%) | 4/6 (66.7%) | 5/6 (83.3%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Polycythaemia | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Thrombocytopenia | 5/8 (62.5%) | 5/8 (62.5%) | 2/6 (33.3%) | 2/6 (33.3%) | 5/11 (45.5%) | 0/2 (0%) | ||||||
| Cardiac disorders | ||||||||||||
| Atrial fibrillation | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Cardiac tamponade | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Cardiomegaly | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Cardiomyopathy | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Mitral valve incompetence | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Pericardial effusion | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Sinus bradycardia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Sinus tachycardia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Supraventricular extrasystoles | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Tachycardia | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Ear and labyrinth disorders | ||||||||||||
| Deafness | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 1/2 (50%) | ||||||
| Ear congestion | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Ear pain | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hearing impaired | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hypoacusis | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Middle ear effusion | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Tinnitus | 2/8 (25%) | 1/8 (12.5%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Endocrine disorders | ||||||||||||
| Hypothyroidism | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Eye disorders | ||||||||||||
| Conjunctivitis | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Diplopia | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Dry eye | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Erythema of eyelid | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Eye swelling | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Eyelid oedema | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Eyelids pruritus | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Lacrimation increased | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Vision blurred | 1/8 (12.5%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Visual disturbance | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal discomfort | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Abdominal distension | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Abdominal pain | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 5/11 (45.5%) | 0/2 (0%) | ||||||
| Abdominal pain upper | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Chapped lips | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Cheilitis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Constipation | 3/8 (37.5%) | 3/8 (37.5%) | 3/6 (50%) | 3/6 (50%) | 6/11 (54.5%) | 0/2 (0%) | ||||||
| Diarrhoea | 0/8 (0%) | 2/8 (25%) | 4/6 (66.7%) | 4/6 (66.7%) | 9/11 (81.8%) | 1/2 (50%) | ||||||
| Dry mouth | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Dyspepsia | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 1/6 (16.7%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Dysphagia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Eructation | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Flatulence | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Gastritis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 1/2 (50%) | ||||||
| Gastrooesophageal reflux disease | 1/8 (12.5%) | 1/8 (12.5%) | 1/6 (16.7%) | 2/6 (33.3%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Gingival bleeding | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Gingival disorder | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Gingival pain | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Haematemesis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Haematochezia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hyperchlorhydria | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Lip dry | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Nausea | 6/8 (75%) | 6/8 (75%) | 5/6 (83.3%) | 6/6 (100%) | 10/11 (90.9%) | 1/2 (50%) | ||||||
| Rectal discharge | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Stomatitis | 1/8 (12.5%) | 1/8 (12.5%) | 2/6 (33.3%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Toothache | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Umbilical hernia | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Vomiting | 4/8 (50%) | 4/8 (50%) | 3/6 (50%) | 4/6 (66.7%) | 6/11 (54.5%) | 0/2 (0%) | ||||||
| General disorders | ||||||||||||
| Adverse drug reaction | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Application site rash | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Asthenia | 0/8 (0%) | 2/8 (25%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Catheter site discharge | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Catheter site erythema | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Catheter site pain | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Catheter site related reaction | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Chest pain | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Crepitations | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Cyst | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 1/2 (50%) | ||||||
| Early satiety | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Extravasation | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Fatigue | 5/8 (62.5%) | 7/8 (87.5%) | 3/6 (50%) | 4/6 (66.7%) | 10/11 (90.9%) | 2/2 (100%) | ||||||
| Generalised oedema | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hypothermia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Impaired healing | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Infusion site reaction | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Injection site bruising | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Injection site reaction | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Mucosal inflammation | 4/8 (50%) | 1/8 (12.5%) | 0/6 (0%) | 5/6 (83.3%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Non-cardiac chest pain | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Oedema | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Oedema peripheral | 1/8 (12.5%) | 1/8 (12.5%) | 2/6 (33.3%) | 2/6 (33.3%) | 0/11 (0%) | 1/2 (50%) | ||||||
| Pain | 1/8 (12.5%) | 1/8 (12.5%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Pyrexia | 1/8 (12.5%) | 1/8 (12.5%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Gallbladder disorder | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Jaundice | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Adenoviral conjunctivitis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Candidiasis | 2/8 (25%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Catheter related infection | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Cellulitis | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Conjunctivitis viral | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Fungal infection | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Herpes zoster | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Infected sebaceous cyst | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Localised infection | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Nail bed infection | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Nasopharyngitis | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Onychomycosis | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Oral candidiasis | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Oral fungal infection | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Otitis media | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Paronychia | 3/8 (37.5%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Pneumonia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Rash pustular | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/6 (16.7%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Respiratory tract infection | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Rhinitis | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Sinusitis | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Tinea pedis | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Tooth abscess | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Upper respiratory tract infection | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Urinary tract infection | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/6 (16.7%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Wound infection | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Muscle strain | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Thermal burn | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Investigations | ||||||||||||
| Alanine aminotransferase increased | 0/8 (0%) | 0/8 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Aspartate aminotransferase | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Aspartate aminotransferase increased | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Blood alkaline phosphatase increased | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Blood magnesium decreased | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Blood phosphorus decreased | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Blood potassium decreased | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Breath sounds abnormal | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Electrocardiogram QT prolonged | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Haemoglobin decreased | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| International normalised ratio increased | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Neutrophil count decreased | 0/8 (0%) | 0/8 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Platelet count decreased | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Platelet count increased | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Prothrombin time ratio increased | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Weight decreased | 1/8 (12.5%) | 0/8 (0%) | 3/6 (50%) | 1/6 (16.7%) | 5/11 (45.5%) | 0/2 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Anorexia | 4/8 (50%) | 4/8 (50%) | 0/6 (0%) | 4/6 (66.7%) | 6/11 (54.5%) | 0/2 (0%) | ||||||
| Appetite disorder | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Decreased appetite | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Dehydration | 3/8 (37.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Hypercalcaemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hypercreatininaemia | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hyperglycaemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Hypocalcaemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hypoglycaemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hypokalaemia | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 4/6 (66.7%) | 6/11 (54.5%) | 1/2 (50%) | ||||||
| Hypomagnesaemia | 2/8 (25%) | 3/8 (37.5%) | 3/6 (50%) | 3/6 (50%) | 6/11 (54.5%) | 2/2 (100%) | ||||||
| Hyponatraemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hypophosphataemia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/6 (16.7%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Back pain | 0/8 (0%) | 0/8 (0%) | 2/6 (33.3%) | 2/6 (33.3%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Flank pain | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Groin pain | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Muscle spasms | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Musculoskeletal chest pain | 0/8 (0%) | 0/8 (0%) | 2/6 (33.3%) | 3/6 (50%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Musculoskeletal pain | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Musculoskeletal stiffness | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Myalgia | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Neck pain | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Pain in extremity | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 1/6 (16.7%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Cancer pain | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Amnesia | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Disturbance in attention | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Dizziness | 1/8 (12.5%) | 2/8 (25%) | 2/6 (33.3%) | 3/6 (50%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Dysarthria | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Dysgeusia | 2/8 (25%) | 2/8 (25%) | 1/6 (16.7%) | 3/6 (50%) | 4/11 (36.4%) | 0/2 (0%) | ||||||
| Facial palsy | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Headache | 1/8 (12.5%) | 2/8 (25%) | 2/6 (33.3%) | 1/6 (16.7%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Hypoaesthesia | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Neuropathy peripheral | 2/8 (25%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Paraesthesia | 0/8 (0%) | 1/8 (12.5%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Sinus headache | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Syncope | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Transient ischaemic attack | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Tremor | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Psychiatric disorders | ||||||||||||
| Abnormal dreams | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Agitation | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Anxiety | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Confusional state | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Depression | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 4/11 (36.4%) | 0/2 (0%) | ||||||
| Insomnia | 0/8 (0%) | 3/8 (37.5%) | 2/6 (33.3%) | 2/6 (33.3%) | 4/11 (36.4%) | 0/2 (0%) | ||||||
| Libido decreased | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Mood altered | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Sleep disorder | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Dysuria | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Pollakiuria | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Proteinuria | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Renal failure | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Reproductive system and breast disorders | ||||||||||||
| Breast tenderness | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Vaginal discharge | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Vaginal haemorrhage | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Asthma | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Atelectasis | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Cough | 0/8 (0%) | 1/8 (12.5%) | 5/6 (83.3%) | 1/6 (16.7%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Dysphonia | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Dyspnoea | 1/8 (12.5%) | 2/8 (25%) | 2/6 (33.3%) | 2/6 (33.3%) | 4/11 (36.4%) | 1/2 (50%) | ||||||
| Dyspnoea exertional | 1/8 (12.5%) | 2/8 (25%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Emphysema | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Epistaxis | 1/8 (12.5%) | 2/8 (25%) | 1/6 (16.7%) | 2/6 (33.3%) | 4/11 (36.4%) | 0/2 (0%) | ||||||
| Haemoptysis | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hiccups | 1/8 (12.5%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Lung infiltration | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Nasal congestion | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Nasal ulcer | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Pharyngolaryngeal pain | 1/8 (12.5%) | 2/8 (25%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Pleural effusion | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Productive cough | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Pulmonary embolism | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Pulmonary hypertension | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Rhinorrhoea | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Sinus congestion | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Throat irritation | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Acne | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 3/11 (27.3%) | 0/2 (0%) | ||||||
| Actinic keratosis | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Alopecia | 1/8 (12.5%) | 2/8 (25%) | 2/6 (33.3%) | 5/6 (83.3%) | 3/11 (27.3%) | 1/2 (50%) | ||||||
| Dermatitis acneiform | 5/8 (62.5%) | 5/8 (62.5%) | 4/6 (66.7%) | 4/6 (66.7%) | 4/11 (36.4%) | 1/2 (50%) | ||||||
| Dermatitis contact | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Dry skin | 1/8 (12.5%) | 2/8 (25%) | 2/6 (33.3%) | 1/6 (16.7%) | 2/11 (18.2%) | 1/2 (50%) | ||||||
| Erythema | 5/8 (62.5%) | 5/8 (62.5%) | 6/6 (100%) | 5/6 (83.3%) | 3/11 (27.3%) | 1/2 (50%) | ||||||
| Exfoliative rash | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 2/11 (18.2%) | 1/2 (50%) | ||||||
| Hyperhidrosis | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Increased tendency to bruise | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Nail disorder | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Night sweats | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Onychoclasis | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Pain of skin | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Pruritus | 5/8 (62.5%) | 2/8 (25%) | 5/6 (83.3%) | 5/6 (83.3%) | 0/11 (0%) | 2/2 (100%) | ||||||
| Rash | 6/8 (75%) | 5/8 (62.5%) | 2/6 (33.3%) | 4/6 (66.7%) | 3/11 (27.3%) | 2/2 (100%) | ||||||
| Rash erythematous | 2/8 (25%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 3/11 (27.3%) | 1/2 (50%) | ||||||
| Rash macular | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Rash maculo-papular | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Rash papular | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Rash pruritic | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 2/11 (18.2%) | 0/2 (0%) | ||||||
| Skin disorder | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Skin exfoliation | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Skin fissures | 2/8 (25%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Skin irritation | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Skin ulcer | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Surgical and medical procedures | ||||||||||||
| Central venous catheterisation | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Deep vein thrombosis | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Flushing | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/2 (0%) | ||||||
| Hot flush | 1/8 (12.5%) | 0/8 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Hypertension | 1/8 (12.5%) | 3/8 (37.5%) | 4/6 (66.7%) | 2/6 (33.3%) | 5/11 (45.5%) | 1/2 (50%) | ||||||
| Hypotension | 0/8 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Jugular vein thrombosis | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Phlebitis | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
| Venous thrombosis limb | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/11 (0%) | 0/2 (0%) | ||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00101907
Other Study ID Numbers:
- 20040206
First Posted:
Jan 19, 2005
Last Update Posted:
Mar 20, 2014
Last Verified:
Feb 1, 2014