Study to Evaluate Motesanib With or Without Carboplatin/Paclitaxel or Panitumumab in the Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00094835
Collaborator
(none)
51
3
25.9
Study Details
Study Description
Brief Summary
The purpose of this trial is: - To characterize the safety profile of motesanib when used in combination with carboplatin/paclitaxel (CP), with panitumumab or with CP and panitumumab in patients with advanced non-small cell lung cancer (NSCLC). - To establish the pharmacokinetic (PK) profile of motesanib when it is used in combination with CP, with panitumumab, or with CP and panitumumab. - To compare the paclitaxel and motesanib PK profiles when the medications are administered 30 minutes (min) or approximately 48 hours (hrs) apart. - To characterize the panitumumab and paclitaxel exposure in the combination regimens of motesanib with CP, motesanib with panitumumab, or motesanib with CP and panitumumab. - To describe the objective response rate (ORR) in each dose cohort. - To measure the immunogenicity of panitumumab in patients administered motesanib with panitumumab and motesanib with CP and panitumumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This was a multicenter, open-label, dose-finding clinical trial examining the safety and PK of once or twice daily motesanib administered with CP or with CP and panitumumab in chemotherapy naïve patients, and with panitumumab in patients with no more than one prior chemotherapy regimen for NSCLC.
Participants were enrolled into the Panitumumab + Paclitaxel + Carboplatin + Motesanib once a safe and tolerable dose of AMG 706 was established in the other treatment arms.
Study Design
Study Type:
Interventional
Actual Enrollment
:
51 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 and Pharmacokinetics (PK) of AMG 706 With Carboplatin/Paclitaxel, AMG 706 With Panitumumab and AMG 706 With Panitumumab and Carboplatin/Paclitaxel in the Treatment of Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC)
Study Start Date
:
Jan 1, 2005
Actual Primary Completion Date
:
Mar 1, 2007
Actual Study Completion Date
:
Mar 1, 2007
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Paclitaxel + Carboplatin + Motesanib Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort and up to 125 mg once daily was used in subsequent cohorts. A cycle was defined as the 3 weeks plus the time to recover from toxicity, if encountered. |
Drug: Motesanib diphosphate
Dose-finding with an initial dose of 50 mg once daily and up to 125 mg once daily. 75 mg twice daily was also to be tested.
Other Names:
Drug: Paclitaxel
Paclitaxel 200 mg/m^2 administered by IV infusion over 3 hours.
Drug: Carboplatin
Carboplatin was administered IV over approximately 30 minutes. Carboplatin was dosed using the glomerular filtration rate (GFR) and Calvert formula to AUC/time curve of 6 mg/mL×min.
|
| Experimental: Panitumumab + Motesanib Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort, up to 125 mg once daily was used in subsequent cohorts. |
Biological: Panitumumab
9.0 mg/kg on Day 1 of each 21-day cycle administered by intravenous infusion over approximately 60 minutes.
Other Names:
Drug: Motesanib diphosphate
Dose-finding with an initial dose of 50 mg once daily and up to 125 mg once daily. 75 mg twice daily was also to be tested.
Other Names:
|
| Experimental: Panitumumab + Paclitaxel + Carboplatin + Motesanib Chemotherapy naïve participants received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants were enrolled in this arm once a safe and tolerable dose of motesanib was established. |
Biological: Panitumumab
9.0 mg/kg on Day 1 of each 21-day cycle administered by intravenous infusion over approximately 60 minutes.
Other Names:
Drug: Motesanib diphosphate
Dose-finding with an initial dose of 50 mg once daily and up to 125 mg once daily. 75 mg twice daily was also to be tested.
Other Names:
Drug: Paclitaxel
Paclitaxel 200 mg/m^2 administered by IV infusion over 3 hours.
Drug: Carboplatin
Carboplatin was administered IV over approximately 30 minutes. Carboplatin was dosed using the glomerular filtration rate (GFR) and Calvert formula to AUC/time curve of 6 mg/mL×min.
|
Outcome Measures
Primary Outcome Measures
- Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1 [Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.]
The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
- Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1 [Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.]
The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
- Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1 [Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.]
The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
- Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1 [Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.]
Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
- Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1 [Cycle 1, Day 3, 24 hours post-dose]
The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
- Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2 [Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.]
The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
- Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2 [Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.]
The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
- Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2 [Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.]
The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
- Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2 [Cycle 2, Day 1 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.]
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
- Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2 [Cycle 2, Day 1, 24 hours post-dose]
The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
Secondary Outcome Measures
- Percentage of Participants With an Overall Objective Response [After 9 weeks of treatment (at the end of Cycle 3)]
Confirmed objective tumor response defined as a complete response (CR) or partial response (PR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Tumor response was evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI). Responding disease (CR or PR) was confirmed no less than 4 weeks after the criteria for response were first met. A complete response defined as the disappearance of all target lesions and all non-target lesions, no new lesions and normalization of tumor marker level. Partial response defined as either the disappearance of all target lesions and the persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diamer (LD) of target lesions, taking as reference the baseline sum LD and no new lesions and/or unequivocal progression of existing non-target lesions.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of unresectable stage IIIB or IV non-small cell lung cancer (NSCLC)
-
No more than one prior chemotherapy
-
Adequate hematologic, renal and hepatic function
-
Measurable disease or evaluable disease on CAT scan or MRI
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Able to fast for 10 hrs twice during the study - Able to tolerate oral medications
-
Life expectancy of at least 3 months
Exclusion Criteria:
-
Symptomatic or untreated central nervous system metastases requiring current treatment
-
History of arterial thrombosis within 1 year prior to enrollment
-
Anticoagulant therapy, except for warfarin of less than 2mg per day
-
Symptomatic peripheral neuropathy
-
History of pulmonary hemorrhage or hemoptysis
-
Myocardial infarction within 1 year before enrollment
-
Uncontrolled hypertension [diastolic greater than 85 mmHg; systolic greater than 145 mmHg]
-
History of other cancer, unless treated with no known active disease for longer than 3 years
-
Previous treatment with AMG 706 or panitumumab, previous treatment with inhibitors of VEGF or EGF
-
No antibody treatment for 6 weeks prior to enrollment
-
Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive
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
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00094835
Other Study ID Numbers:
- 20040153
- NCT00107224
First Posted:
Oct 27, 2004
Last Update Posted:
Mar 24, 2016
Last Verified:
Feb 1, 2016
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled from 18 January 2005 through 25 September 2006 |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Period Title: Overall Study | |||||||
| STARTED | 9 | 11 | 7 | 5 | 7 | 6 | 6 |
| Treated With Motesanib | 6 | 11 | 6 | 4 | 7 | 5 | 6 |
| COMPLETED | 5 | 8 | 4 | 4 | 3 | 3 | 4 |
| NOT COMPLETED | 4 | 3 | 3 | 1 | 4 | 3 | 2 |
Baseline Characteristics
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Total of all reporting groups |
| Overall Participants | 6 | 11 | 6 | 4 | 7 | 5 | 6 | 45 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
67.8
(7.8)
|
55.7
(12.7)
|
64.5
(6.1)
|
57.5
(9.9)
|
64.0
(9.6)
|
51.6
(14.6)
|
59.0
(5.5)
|
59.9
(10.8)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
0
0%
|
4
36.4%
|
3
50%
|
0
0%
|
5
71.4%
|
1
20%
|
3
50%
|
16
35.6%
|
| Male |
6
100%
|
7
63.6%
|
3
50%
|
4
100%
|
2
28.6%
|
4
80%
|
3
50%
|
29
64.4%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||||||
| White or Caucasian |
6
100%
|
11
100%
|
5
83.3%
|
4
100%
|
6
85.7%
|
4
80%
|
5
83.3%
|
41
91.1%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
2
4.4%
|
| Black or African American |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
2
4.4%
|
Outcome Measures
| Title | Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1 |
|---|---|
| Description | The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose. |
| Time Frame | Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic (PK) population consisted of all consented patients who received motesanib and had evaluable pharmacokinetic data and did not have significant protocol deviations that affected the data or key-dosing information that was missing. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 4 | 9 | 6 | 4 | 6 | 3 | 3 |
| Median (Full Range) [hours] |
0.75
|
1.0
|
0.75
|
1.5
|
1.0
|
0.58
|
1.0
|
| Title | Percentage of Participants With an Overall Objective Response |
|---|---|
| Description | Confirmed objective tumor response defined as a complete response (CR) or partial response (PR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Tumor response was evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI). Responding disease (CR or PR) was confirmed no less than 4 weeks after the criteria for response were first met. A complete response defined as the disappearance of all target lesions and all non-target lesions, no new lesions and normalization of tumor marker level. Partial response defined as either the disappearance of all target lesions and the persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diamer (LD) of target lesions, taking as reference the baseline sum LD and no new lesions and/or unequivocal progression of existing non-target lesions. |
| Time Frame | After 9 weeks of treatment (at the end of Cycle 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy analysis set, composed of all enrolled participants who received at least one dose of motesanib in treatment arms 1-3 or at least one dose of motesanib with one dose of panitumumab in treatmnt arms 4-7. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 6 | 11 | 6 | 4 | 7 | 5 | 6 |
| Number [Percentage of participants] |
33
550%
|
18
163.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
17
283.3%
|
| Title | Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1 |
|---|---|
| Description | The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose. |
| Time Frame | Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 4 | 9 | 6 | 4 | 6 | 3 | 3 |
| Mean (Standard Deviation) [ng/mL] |
158
(55)
|
525
(250)
|
448
(112)
|
328
(214)
|
444
(130)
|
198
(55)
|
360
(243)
|
| Title | Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1 |
|---|---|
| Description | The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose. |
| Time Frame | Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for the Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD treatment group for which the sample size was smaller than 3. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID |
|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 3 | 7 | 6 | 4 | 4 | 3 |
| Mean (Standard Deviation) [hours] |
7.34
(2.07)
|
5.33
(1.05)
|
5.77
(1.45)
|
6.47
(2.31)
|
7.57
(2.60)
|
8.28
(2.62)
|
| Title | Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1 |
|---|---|
| Description | Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose. |
| Time Frame | Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for the Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD treatment group for which the sample size was smaller than 3. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID |
|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 3 | 7 | 5 | 4 | 4 | 3 |
| Mean (Standard Deviation) [μg*hr/mL] |
0.971
(0.300)
|
3.21
(1.12)
|
2.91
(1.01)
|
1.74
(0.63)
|
3.23
(1.83)
|
2.04
(1.06)
|
| Title | Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1 |
|---|---|
| Description | The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose). |
| Time Frame | Cycle 1, Day 3, 24 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for the Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD treatment group for which the sample size was smaller than 3. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID |
|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 3 | 9 | 5 | 4 | 4 | 3 |
| Mean (Standard Deviation) [ng/mL] |
9.12
(4.17)
|
26.5
(16.8)
|
56.7
(27.4)
|
14.0
(11.7)
|
32.5
(21.5)
|
56.8
(21.1)
|
| Title | Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2 |
|---|---|
| Description | The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose. |
| Time Frame | Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 4 | 9 | 6 | 4 | 6 | 3 | 3 |
| Median (Full Range) [hours] |
1.5
|
1.0
|
0.63
|
1.0
|
0.75
|
1.0
|
2.0
|
| Title | Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2 |
|---|---|
| Description | The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose. |
| Time Frame | Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 4 | 9 | 6 | 4 | 6 | 3 | 3 |
| Mean (Standard Deviation) [ng/mL] |
148
(25)
|
748
(701)
|
390
(319)
|
265
(190)
|
672
(336)
|
242
(153)
|
651
(605)
|
| Title | Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2 |
|---|---|
| Description | The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose. |
| Time Frame | Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for three treatment groups for which the sample size was smaller than 3. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD |
|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 5 | 5 | 3 | 3 |
| Mean (Standard Deviation) [hours] |
6.41
(2.08)
|
6.36
(1.70)
|
7.08
(0.35)
|
4.90
(1.21)
|
| Title | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2 |
|---|---|
| Description | Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose. |
| Time Frame | Cycle 2, Day 1 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for two treatment groups for which the sample size was smaller than 3. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 5 | 5 | 3 | 5 | 3 |
| Mean (Standard Deviation) [μg*hr/mL] |
4.50
(2.62)
|
3.11
(2.38)
|
1.26
(0.61)
|
3.92
(2.65)
|
3.16
(1.20)
|
| Title | Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2 |
|---|---|
| Description | The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose). |
| Time Frame | Cycle 2, Day 1, 24 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for two treatment groups for which the sample size was smaller than 3. |
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. |
| Measure Participants | 5 | 5 | 3 | 5 | 3 |
| Mean (Standard Deviation) [ng/mL] |
43.4
(44.8)
|
45.4
(35.9)
|
10.4
(5.3)
|
61.1
(72.6)
|
45.1
(37.9)
|
Adverse Events
| Time Frame | First dose through 30 days after last dose; maximum time on treatment was 322 days. | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in any treatment arm. | |||||||||||||
| Arm/Group Title | Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD | |||||||
| Arm/Group Description | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. | |||||||
All Cause Mortality |
||||||||||||||
| Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD | ||||||||
| 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) | |||||||
Serious Adverse Events |
||||||||||||||
| Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD | ||||||||
| 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 | 5/6 (83.3%) | 2/11 (18.2%) | 3/6 (50%) | 0/4 (0%) | 1/7 (14.3%) | 4/5 (80%) | 2/6 (33.3%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Febrile neutropenia | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pancytopenia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Cardiac disorders | ||||||||||||||
| Atrial fibrillation | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Endocrine disorders | ||||||||||||||
| Adrenal insufficiency | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal pain | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 1/6 (16.7%) | |||||||
| Diarrhoea | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Gastrointestinal haemorrhage | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Nausea | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 1/6 (16.7%) | |||||||
| Pancreatitis | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Vomiting | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| General disorders | ||||||||||||||
| Fatigue | 1/6 (16.7%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Non-cardiac chest pain | 1/6 (16.7%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pyrexia | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hepatobiliary disorders | ||||||||||||||
| Cholecystitis | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 2/5 (40%) | 0/6 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Pneumonia | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Staphylococcal sepsis | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Urinary tract infection | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Femur fracture | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Anorexia | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Dehydration | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypovolaemia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Metastases to central nervous system | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Non-small cell lung cancer | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Cognitive disorder | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Encephalopathy | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Vocal cord paralysis | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Confusional state | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Mental status changes | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Renal failure acute | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Cough | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Dyspnoea | 2/6 (33.3%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Dyspnoea exacerbated | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypoxia | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Interstitial lung disease | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pulmonary embolism | 2/6 (33.3%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Rash | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Hypotension | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Orthostatic hypotension | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
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| Paclitaxel/Carboplatin + Motesanib 50 mg QD | Paclitaxel/Carboplatin + Motesanib 125 mg QD | Paclitaxel/Carboplatin + Motesanib 75 mg BID | Panitumumab + Motesanib 50 mg QD | Panitumumab + Motesanib 125 mg QD | Panitumumab + Motesanib 75 mg BID | Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD | ||||||||
| 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 | 6/6 (100%) | 11/11 (100%) | 6/6 (100%) | 4/4 (100%) | 7/7 (100%) | 5/5 (100%) | 6/6 (100%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 2/5 (40%) | 1/6 (16.7%) | |||||||
| Leukopenia | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Neutropenia | 0/6 (0%) | 2/11 (18.2%) | 1/6 (16.7%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Thrombocytopenia | 1/6 (16.7%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Cardiac disorders | ||||||||||||||
| Atrial fibrillation | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Conduction disorder | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Sinus tachycardia | 1/6 (16.7%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Tachycardia | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Deafness | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 2/6 (33.3%) | |||||||
| Ear discomfort | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Eye disorders | ||||||||||||||
| Conjunctivitis | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Diplopia | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Dry eye | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Vision blurred | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 2/6 (33.3%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal discomfort | 1/6 (16.7%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Abdominal distension | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Abdominal pain | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 1/4 (25%) | 0/7 (0%) | 2/5 (40%) | 0/6 (0%) | |||||||
| Abdominal pain lower | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Abdominal pain upper | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Ascites | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Change of bowel habit | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Chapped lips | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Colitis | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Constipation | 2/6 (33.3%) | 2/11 (18.2%) | 1/6 (16.7%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Diarrhoea | 3/6 (50%) | 7/11 (63.6%) | 6/6 (100%) | 0/4 (0%) | 5/7 (71.4%) | 3/5 (60%) | 5/6 (83.3%) | |||||||
| Dyspepsia | 2/6 (33.3%) | 3/11 (27.3%) | 1/6 (16.7%) | 0/4 (0%) | 1/7 (14.3%) | 1/5 (20%) | 3/6 (50%) | |||||||
| Dysphagia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Flatulence | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 2/6 (33.3%) | |||||||
| Gastrointestinal pain | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Gastrooesophageal reflux disease | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Gingival pain | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Gingival ulceration | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Hyperchlorhydria | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Inguinal hernia | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Mouth ulceration | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Nausea | 4/6 (66.7%) | 6/11 (54.5%) | 5/6 (83.3%) | 1/4 (25%) | 3/7 (42.9%) | 2/5 (40%) | 4/6 (66.7%) | |||||||
| Odynophagia | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Oesophagitis | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Oral pain | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Stomatitis | 0/6 (0%) | 3/11 (27.3%) | 2/6 (33.3%) | 0/4 (0%) | 3/7 (42.9%) | 1/5 (20%) | 4/6 (66.7%) | |||||||
| Vomiting | 4/6 (66.7%) | 4/11 (36.4%) | 5/6 (83.3%) | 0/4 (0%) | 1/7 (14.3%) | 4/5 (80%) | 1/6 (16.7%) | |||||||
| General disorders | ||||||||||||||
| Adverse drug reaction | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Chest discomfort | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Chest pain | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Chills | 0/6 (0%) | 1/11 (9.1%) | 2/6 (33.3%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Early satiety | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Fatigue | 5/6 (83.3%) | 8/11 (72.7%) | 4/6 (66.7%) | 2/4 (50%) | 6/7 (85.7%) | 5/5 (100%) | 5/6 (83.3%) | |||||||
| Hypothermia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Infusion site pain | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Irritability | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Localised oedema | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Mucosal inflammation | 0/6 (0%) | 2/11 (18.2%) | 1/6 (16.7%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Non-cardiac chest pain | 2/6 (33.3%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Oedema | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Oedema peripheral | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Pain | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pyrexia | 1/6 (16.7%) | 1/11 (9.1%) | 2/6 (33.3%) | 0/4 (0%) | 0/7 (0%) | 3/5 (60%) | 1/6 (16.7%) | |||||||
| Temperature intolerance | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hepatobiliary disorders | ||||||||||||||
| Cholecystitis | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Immune system disorders | ||||||||||||||
| Hypersensitivity | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Infections and infestations | ||||||||||||||
| Candidiasis | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Cystitis | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Escherichia bacteraemia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Eye infection | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Folliculitis | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Fungal infection | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Gastroenteritis | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Herpes simplex | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Infected cyst | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Infection | 1/6 (16.7%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Liver abscess | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Lymph gland infection | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Oral candidiasis | 0/6 (0%) | 2/11 (18.2%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Oral infection | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Paronychia | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 1/7 (14.3%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Respiratory tract infection | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Rhinitis | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Sinusitis | 3/6 (50%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Staphylococcal infection | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Subcutaneous abscess | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Tooth abscess | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Tooth infection | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Upper respiratory tract infection | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Urinary tract infection | 0/6 (0%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Incision site complication | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Investigations | ||||||||||||||
| Blood creatinine increased | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Breath sounds abnormal | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Haemoglobin decreased | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Weight decreased | 1/6 (16.7%) | 4/11 (36.4%) | 2/6 (33.3%) | 1/4 (25%) | 2/7 (28.6%) | 2/5 (40%) | 2/6 (33.3%) | |||||||
| White blood cell count decreased | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Anorexia | 0/6 (0%) | 2/11 (18.2%) | 3/6 (50%) | 1/4 (25%) | 4/7 (57.1%) | 2/5 (40%) | 1/6 (16.7%) | |||||||
| Decreased appetite | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Dehydration | 1/6 (16.7%) | 1/11 (9.1%) | 2/6 (33.3%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypercalcaemia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hyperkalaemia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypoalbuminaemia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypocalcaemia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypokalaemia | 0/6 (0%) | 4/11 (36.4%) | 3/6 (50%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Hypomagnesaemia | 1/6 (16.7%) | 5/11 (45.5%) | 5/6 (83.3%) | 2/4 (50%) | 3/7 (42.9%) | 4/5 (80%) | 2/6 (33.3%) | |||||||
| Hyponatraemia | 0/6 (0%) | 0/11 (0%) | 3/6 (50%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Hypophosphataemia | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 0/6 (0%) | 3/11 (27.3%) | 3/6 (50%) | 0/4 (0%) | 2/7 (28.6%) | 1/5 (20%) | 3/6 (50%) | |||||||
| Back pain | 1/6 (16.7%) | 0/11 (0%) | 2/6 (33.3%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Muscle spasms | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Muscular weakness | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Musculoskeletal chest pain | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Musculoskeletal pain | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Myalgia | 2/6 (33.3%) | 6/11 (54.5%) | 1/6 (16.7%) | 0/4 (0%) | 4/7 (57.1%) | 0/5 (0%) | 2/6 (33.3%) | |||||||
| Neck pain | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pain in extremity | 1/6 (16.7%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 4/6 (66.7%) | |||||||
| Shoulder pain | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Metastases to central nervous system | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Balance disorder | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Cognitive disorder | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Coordination abnormal | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Dizziness | 2/6 (33.3%) | 1/11 (9.1%) | 2/6 (33.3%) | 0/4 (0%) | 1/7 (14.3%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Dysarthria | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Dysgeusia | 0/6 (0%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/4 (0%) | 1/7 (14.3%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Headache | 1/6 (16.7%) | 4/11 (36.4%) | 3/6 (50%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Hypoaesthesia | 0/6 (0%) | 2/11 (18.2%) | 1/6 (16.7%) | 0/4 (0%) | 1/7 (14.3%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Memory impairment | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 2/5 (40%) | 0/6 (0%) | |||||||
| Mental impairment | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Neuropathy | 4/6 (66.7%) | 3/11 (27.3%) | 2/6 (33.3%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 3/6 (50%) | |||||||
| Neuropathy peripheral | 1/6 (16.7%) | 2/11 (18.2%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Paraesthesia | 1/6 (16.7%) | 3/11 (27.3%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Peripheral sensory neuropathy | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Restless legs syndrome | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Speech disorder | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Tremor | 1/6 (16.7%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Anxiety | 0/6 (0%) | 2/11 (18.2%) | 1/6 (16.7%) | 1/4 (25%) | 0/7 (0%) | 1/5 (20%) | 1/6 (16.7%) | |||||||
| Confusional state | 1/6 (16.7%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Depression | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Insomnia | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 1/4 (25%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Mental status changes | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Personality change | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Bladder pain | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Haematuria | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Haemorrhage urinary tract | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Incontinence | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Micturition urgency | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Pollakiuria | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Proteinuria | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Reproductive system and breast disorders | ||||||||||||||
| Pelvic discomfort | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Allergic cough | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Cough | 1/6 (16.7%) | 3/11 (27.3%) | 2/6 (33.3%) | 1/4 (25%) | 2/7 (28.6%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Dysphonia | 2/6 (33.3%) | 3/11 (27.3%) | 1/6 (16.7%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Dyspnoea | 4/6 (66.7%) | 4/11 (36.4%) | 2/6 (33.3%) | 0/4 (0%) | 3/7 (42.9%) | 0/5 (0%) | 2/6 (33.3%) | |||||||
| Dyspnoea exacerbated | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Epistaxis | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 4/7 (57.1%) | 1/5 (20%) | 2/6 (33.3%) | |||||||
| Haemoptysis | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Hiccups | 1/6 (16.7%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypoxia | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pharyngolaryngeal pain | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Pleural rub | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pleuritic pain | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pulmonary embolism | 1/6 (16.7%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Pulmonary haemorrhage | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Rales | 0/6 (0%) | 2/11 (18.2%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Rhinitis allergic | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Rhinorrhoea | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Sinus congestion | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Acne | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Alopecia | 2/6 (33.3%) | 4/11 (36.4%) | 1/6 (16.7%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 4/6 (66.7%) | |||||||
| Dermatitis | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 1/4 (25%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Dermatitis acneiform | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 1/4 (25%) | 3/7 (42.9%) | 3/5 (60%) | 6/6 (100%) | |||||||
| Dry skin | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 3/7 (42.9%) | 1/5 (20%) | 1/6 (16.7%) | |||||||
| Erythema | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 2/4 (50%) | 2/7 (28.6%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Exfoliative rash | 0/6 (0%) | 1/11 (9.1%) | 1/6 (16.7%) | 3/4 (75%) | 3/7 (42.9%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hyperhidrosis | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Nail disorder | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Night sweats | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pain of skin | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Palmar erythema | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Pruritus | 1/6 (16.7%) | 2/11 (18.2%) | 0/6 (0%) | 0/4 (0%) | 6/7 (85.7%) | 3/5 (60%) | 3/6 (50%) | |||||||
| Rash | 0/6 (0%) | 3/11 (27.3%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 2/5 (40%) | 0/6 (0%) | |||||||
| Rash erythematous | 0/6 (0%) | 2/11 (18.2%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Rash follicular | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Rash generalised | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Rash maculo-papular | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Rash pruritic | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 1/5 (20%) | 0/6 (0%) | |||||||
| Skin fissures | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Skin lesion | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Skin ulcer | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Deep vein thrombosis | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
| Flushing | 1/6 (16.7%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hot flush | 0/6 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Hypertension | 4/6 (66.7%) | 5/11 (45.5%) | 4/6 (66.7%) | 1/4 (25%) | 4/7 (57.1%) | 3/5 (60%) | 3/6 (50%) | |||||||
| Hypotension | 3/6 (50%) | 3/11 (27.3%) | 2/6 (33.3%) | 0/4 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Orthostatic hypotension | 0/6 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Phlebitis | 0/6 (0%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/6 (0%) | |||||||
| Thrombosis | 1/6 (16.7%) | 0/11 (0%) | 0/6 (0%) | 0/4 (0%) | 0/7 (0%) | 0/5 (0%) | 1/6 (16.7%) | |||||||
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:
NCT00094835
Other Study ID Numbers:
- 20040153
- NCT00107224
First Posted:
Oct 27, 2004
Last Update Posted:
Mar 24, 2016
Last Verified:
Feb 1, 2016