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Trial record 33 of 125 for:    lapatinib | Recruiting, Active, not recruiting, Completed Studies | Phase 2

Pazopanib In Combination With Lapatinib In Adult Patients With Relapsed Malignant Glioma (VEG102857)

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ClinicalTrials.gov Identifier: NCT00350727
Recruitment Status : Completed
First Posted : July 11, 2006
Results First Posted : June 20, 2011
Last Update Posted : April 19, 2013
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioma
Interventions Drug: pazopanib
Drug: lapatinib
Enrollment 75
Recruitment Details Phase I and Phase II had two separate participant populations. Enrollment in Phase II was not dependent on the number of participants completing Phase I.
Pre-assignment Details  
Arm/Group Title Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort. All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN). All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Period Title: Phase I: Dose Escalation
Started 34 0 0
Completed 0 0 0
Not Completed 34 0 0
Reason Not Completed
Adverse Event             4             0             0
Lack of Efficacy             25             0             0
Death             1             0             0
Physician Decision             1             0             0
Transition to Extension Phase             3             0             0
Period Title: Phase II
Started 0 19 22
Completed 0 0 0
Not Completed 0 19 22
Reason Not Completed
Disease Progression             0             15             16
Clinical Deterioration             0             1             0
Withdrawal by Subject             0             2             1
Adverse Event             0             1             1
Death             0             0             2
Sponsor Terminated Study             0             0             1
Enrolled in Rollover Study             0             0             1
Arm/Group Title Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative Total
Hide Arm/Group Description Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort. All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN). All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN. Total of all reporting groups
Overall Number of Baseline Participants 34 19 22 75
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants 19 participants 22 participants 75 participants
20-29 years old 1 0 2 3
30-39 years old 8 0 3 11
40-49 years old 11 6 6 23
50-59 years old 10 5 8 23
60-69 years old 3 7 2 12
>=70 years old 1 1 1 3
[1]
Measure Description: Number of participants falling into the indicated age groups.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 19 participants 22 participants 75 participants
Female
11
  32.4%
5
  26.3%
5
  22.7%
21
  28.0%
Male
23
  67.6%
14
  73.7%
17
  77.3%
54
  72.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants 19 participants 22 participants 75 participants
African American/African Heritage 0 0 1 1
White/Caucasian/European Heritage 34 19 21 74
1.Primary Outcome
Title Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
Hide Description Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Time Frame Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population (all participants who were given any dose of study medication) for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.
Arm/Group Title Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort.
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 33 19 22
Measure Type: Number
Unit of Measure: participants
BL, 90-<140 mmHg; shift to post-BL, 90-<140 mmgHg 21 12 11
BL, 90-<140 mmHg; shift to post-BL, 140-<170 mmHg 12 3 8
BL, 90-<140 mmHg; shift to post-BL, >=170 mmHg 0 0 1
BL, 140-<170 mmHg; shift to post-BL, 90-<140 mmHg 0 1 0
BL, 140-<170 mmHg; shift to post-BL, 140-<170 mmHg 0 2 1
BL, 140-<170 mmHg; shift to post-BL, >=170 mmHg 0 0 0
BL, >=170 mmHg; shift to post-BL, 140-<170 mmHg 0 1 1
2.Primary Outcome
Title Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
Hide Description Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Time Frame Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.
Arm/Group Title Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort.
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 33 19 22
Measure Type: Number
Unit of Measure: participants
BL, 50-<90 mmHg; shift to post-BL, 50-<90 mmHg 23 13 9
BL, 50-<90 mmHg; shift to post-BL, 90-<110 mmHg 9 4 10
BL, 90-<110 mmHg; shift to post-BL, 50-<90 mmHg 0 1 0
BL, 90-<110 mmHg; shift to post-BL, 90-<110 mmHg 1 0 2
BL, 90-<110 mmHg; shift to post-BL, >=110 mmHg 0 1 1
3.Primary Outcome
Title Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
Hide Description Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. bpm, beats per minute.
Time Frame Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.
Arm/Group Title Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort.
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 33 19 22
Measure Type: Number
Unit of Measure: participants
BL, 44-100 bpm; shift to post-BL, 44-100 bpm 31 14 19
BL, 44-100 bpm; shift to post-BL, 101-120 bpm 0 3 2
BL, 101-120 bpm; shift to post-BL, 101-120 bpm 2 0 0
BL, 101-120 bpm; shift to post-BL, >120 bpm 0 1 0
BL, >120 bpm; shift to post-BL, 44-100 bpm 0 0 1
BL, missing; shift to post-BL, 44-100 bpm 0 1 0
4.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 21
Mean (Standard Deviation)
Unit of Measure: grams per liter (g/L)
-5.9  (9.57) -6.7  (9.95)
5.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Mean (Standard Deviation)
Unit of Measure: International Units per Liter (IU/L)
Alkaline phosphatase, n=19, 21 18.6  (54.02) 33.9  (109.99)
Alanine aminotransferase, n=19, 22 56.1  (131.99) 132.7  (393.89)
Aspartate aminotransferase, n=19, 22 36.4  (88.50) 52.7  (178.02)
Lactate dehydrogenase, n=18, 19 291.50  (443.725) 171.63  (606.986)
6.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: Units per liter (U/L)
Amylase 22.72  (28.060) 20.05  (30.288)
Lipase 131.4  (318.13) 120.5  (163.51)
7.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 21
Mean (Standard Deviation)
Unit of Measure: micromoles per liter (µmol/l)
Total bilirubin 6.174  (7.2714) 23.562  (71.1671)
Creatinine 6.93  (10.444) 9.59  (14.852)
8.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 21
Mean (Standard Deviation)
Unit of Measure: millimoles per liter (mmol/l)
Calcium, n=19, 21 0.004  (0.1257) 0.019  (0.0952)
Glucose, n=19, 21 0.082  (4.1342) 1.850  (2.7180)
Potassium, n=19, 21 0.17  (0.471) 0.30  (0.264)
Magnesium, n=19, 19 0.022  (0.0676) 0.040  (0.0853)
Sodium, n=19, 21 1.7  (2.96) 1.3  (1.85)
Urea, n=19, 21 0.770  (1.6840) 1.071  (2.1736)
Inorganic phosphorus, n=19, 20 0.090  (0.2352) 0.076  (0.2048)
9.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine)
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 16 13
Mean (Standard Deviation)
Unit of Measure: picomoles per liter (pmol/l)
Thyroxine, n=16, 13 -8.052  (30.2175) 10.806  (40.5626)
Free T3, n=4, 4 0.420  (0.5010) -2.442  (2.3525)
10.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 18 20
Mean (Standard Deviation)
Unit of Measure: milliunits per liter (mU/L)
1.37  (2.106) 2.59  (4.377)
11.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 13 8
Mean (Standard Deviation)
Unit of Measure: nanomoles per liter (nmol/l)
-0.181  (0.6521) -0.104  (0.3516)
12.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Mean (Standard Deviation)
Unit of Measure: grams per liter (g/L)
-4.6  (11.25) -8.0  (16.75)
13.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Mean (Standard Deviation)
Unit of Measure: percent
-0.016  (0.0320) -0.027  (0.0452)
14.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Mean (Standard Deviation)
Unit of Measure: giga (10^9) per liter (GI/L)
Lymphocytes, n=16, 19 -0.26  (0.556) -0.21  (0.573)
Total Neutrophils, n=16, 18 -2.87  (3.021) -4.72  (5.067)
Platelet count, n=19, 22 -58.7  (53.98) -55.7  (59.79)
White blood cells, n=19, 22 -2.63  (2.934) -4.06  (6.026)
15.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time)
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Mean (Standard Deviation)
Unit of Measure: ratio
0.030  (0.0663) 0.042  (0.1094)
16.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Time Frame Baseline to study completion (up to 878 days for Phase II)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Mean (Standard Deviation)
Unit of Measure: seconds (sec)
Partial thromboplastin time 2.10  (1.985) 2.62  (3.175)
Prothrombin time 0.0  (0.57) 0.2  (1.19)
17.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg /Lapatinib 1500 mg Phase I: Pazopanib 800 mg /Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Mean (Standard Deviation)
Unit of Measure: grams per liter (g/L)
-4.25  (4.573) -6.17  (5.707) -3.80  (1.924) -5.17  (3.545) -13.66  (16.959) -7.17  (4.215)
18.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Mean (Standard Deviation)
Unit of Measure: International Units per Liter (IU/L)
Alkaline phosphatase 9.8  (11.47) 22.8  (39.55) 31.2  (53.60) 15.8  (22.66) 22.0  (28.54) 22.0  (47.15)
Alanine aminotransferase 36.8  (66.35) 139.5  (204.81) 47.0  (48.09) 33.2  (25.25) 4.8  (7.19) 47.7  (56.43)
Aspartate aminotransferase 15.0  (31.72) 49.3  (71.63) 13.8  (15.71) 8.8  (7.03) 13.5  (16.20) 19.3  (18.47)
Lactate dehydrogenase 148.0  (96.42) 127.0  (144.60) 46.0  (35.86) 321.2  (534.42) 124.7  (136.46) 116.8  (59.26)
19.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Mean (Standard Deviation)
Unit of Measure: Units per liter (U/L)
Amylase 24.3  (36.42) 24.4  (17.04) 27.3  (66.4) 31.0  (38.96) 44.4  (52.52) 23.3  (39.38)
Lipase 147.0  (292.02) 23.3  (44.98) 33.0  (56.79) 151.8  (230.63) 67.3  (101.83) 7.8  (21.09)
20.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Mean (Standard Deviation)
Unit of Measure: micromoles per liter (µmol/l)
Total bilirubin -0.000  (4.6307) 2.613  (2.5162) 3.368  (2.1520) 6.130  (6.0799) 4.135  (3.8089) 6.398  (3.8952)
Creatinine 4.420  (15.3113) 8.367  (11.3656) 7.336  (6.6049) 6.893  (6.6297) 9.727  (9.7448) 12.005  (19.3179)
21.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Mean (Standard Deviation)
Unit of Measure: millimoles per liter (mmol/l)
Calcium -0.062  (0.0250) -0.045  (0.1173) 0.036  (0.0572) 0.061  (0.0874) 0.047  (0.1155) -0.014  (0.1166)
Glucose 0.56  (1.385) 3.35  (6.653) 1.20  (1.114) 1.02  (2.654) 1.55  (0.589) 0.65  (0.934)
Potassium 0.075  (0.4992) 0.400  (0.3033) 0.420  (0.3033) 0.500  (0.2608) 0.600  (0.5967) 0.183  (0.2229)
Magnesium 0.069  (0.0237) -0.019  (0.0573) 0.058  (0.0463) 0.051  (0.0510) 0.043  (0.0615) 0.056  (0.0920)
Sodium -1.000  (1.8257) 0.500  (2.0736) 1.800  (1.6432) 1.333  (2.0656) 1.500  (4.5497) 0.000  (0.6325)
Urea 1.9  (0.18) 0.6  (1.18) 0.8  (1.74) 1.1  (1.27) 0.9  (1.20) 1.7  (1.72)
Inorganic phosphorus 0.02  (0.168) 0.11  (0.186) 0.41  (0.553) 0.16  (0.164) 0.01  (0.129) 0.25  (0.185)
22.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Mean (Standard Deviation)
Unit of Measure: picomoles per liter (pmol/l)
-0.740  (2.8496) -1.498  (1.8681) 1.105  (3.6173) 1.879  (2.8191) 0.377  (3.9731) -0.781  (1.0040)
23.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine)
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline. For some arms, data were not collected for either baseline or post-baseline assessments.
Arm/Group Title Phase I: Pazopanib 200 mg /Lapatinib 1500 mg Phase I: Pazopanib 800 mg /Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 0 0 5 0 6 0
Mean (Standard Deviation)
Unit of Measure: picomoles per liter (pmol/l)
-0.07  (0.222) -0.94  (1.291)
24.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Mean (Standard Deviation)
Unit of Measure: milliunits per liter (mU/L)
-0.5068  (1.99588) 0.1900  (0.38931) 0.6543  (0.73309) 0.6660  (0.70497) 0.6080  (11.10117) 2.2940  (1.25335)
25.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline. For some arms, data were not collected for either baseline or post-baseline assessments.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 0 7 0 0
Mean (Standard Deviation)
Unit of Measure: nanomoles per liter (nmol/l)
-0.071  (0.1113) 0.214  (0.2851) 0.004  (0.0028)
26.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 6 6 6
Mean (Standard Deviation)
Unit of Measure: grams per Liter (g/L)
-7.25  (14.975) -7.83  (12.999) -4.80  (9.834) -3.33  (13.095) -16.17  (9.867) -21.02  (59.642)
27.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 6 6 6
Mean (Standard Deviation)
Unit of Measure: percent
-0.02  (0.034) -0.02  (0.029) -0.02  (0.023) 0.00  (0.027) -0.09  (0.103) 0.01  (0.024)
28.Primary Outcome
Title Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 6 6 6
Mean (Standard Deviation)
Unit of Measure: giga (10^9) per liter (GI/L)
Lymphocytes, n=3, 6, 4, 6, 6, 6 -0.377  (0.4611) -0.120  (0.4291) -0.153  (0.3083) -0.032  (0.2807) -0.218  (0.2316) -0.250  (0.3017)
Total Neutrophils, n=3, 6, 4, 6, 6, 6 -0.693  (1.0775) -3.000  (3.2727) -1.370  (1.5036) -0.595  (0.8783) -1.723  (1.7320) -0.617  (2.7154)
Platelet count, n=4, 6, 5, 6, 6, 6 -12.3  (30.08) -74.7  (74.18) -65.4  (32.65) -25.3  (40.00) -35.5  (54.72) -61.8  (32.17)
White blood cell count, n=4, 6, 5, 6, 6, 6 -0.845  (1.0849) -2.933  (3.6335) -1.950  (2.1249) -0.850  (0.9072) -1.717  (2.2355) -0.850  (2.4468)
29.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time)
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phases I and II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 6 6 5
Mean (Standard Deviation)
Unit of Measure: ratio
0.077  (0.0866) -0.023  (0.0638) 0.056  (0.0472) 0.000  (0.1097) 0.015  (0.0764) 0.006  (0.0134)
30.Primary Outcome
Title Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time
Hide Description Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Time Frame Baseline to study completion (up to 844 days for Phase I)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 6 6 5
Mean (Standard Deviation)
Unit of Measure: seconds (sec)
Partial thromboplastin time 1.10  (1.299) 2.88  (1.986) 2.62  (5.545) -0.38  (6.122) 2.18  (2.082) 1.00  (1.093)
Prothrombin time 0.38  (0.532) 0.47  (0.940) 0.64  (0.981) -0.02  (0.796) 1.07  (1.722) 0.56  (0.885)
31.Primary Outcome
Title Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose
Hide Description A dose-limiting toxicity (DLT) is defined as predefined adverse events or events that prevented participants from receiving 75% of their scheduled doses or from starting their next treatment period. The dose at which no more than 1 out of 6 participants experiences a DLT is defined as the optimally tolerated regimen. The OTR is important because it determines the highest dose combination that can be given without significant toxicity.
Time Frame Cycle 1 in Phase I (up to Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase I
Arm/Group Title Phase I: Pazopanib 200 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 1500 mg Phase I: Pazopanib 800 mg/Lapatinib 500 mg Phase I: Pazopanib 800 mg/Lapatinib 750 mg Phase I: Pazopanib 800 mg/Lapatinib 1000 mg Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Hide Arm/Group Description:
Pazopanib 200 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 1500 mg OD
Pazopanib 800 mg OD and Lapatinib 500 mg BID
Pazopanib 800 mg OD and Lapatinib 750 mg BID
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
Overall Number of Participants Analyzed 4 6 5 7 6 6
Measure Type: Number
Unit of Measure: participants
0 1 1 1 1 1
32.Primary Outcome
Title Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
Hide Description OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Time Frame Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population in Phase II who also had a response assessment
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed EGFRvIII and/or PTEN.
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Measure Type: Number
Unit of Measure: participants
Complete response 0 0
Partial response 1 2
Stable disease, >=8 weeks 7 6
Progressive disease, <8 weeks 7 8
Progressive disease 4 6
33.Primary Outcome
Title Overall Response (OR) in Phase II Based on the Investigator-assigned Response
Hide Description OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Time Frame Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II who also had a response assessment.
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Measure Type: Number
Unit of Measure: participants
Complete response 0 0
Partial response 1 1
Stable disease, >=8 weeks 7 7
Progressive disease, <8 weeks 7 9
Progressive disease 4 5
34.Primary Outcome
Title Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Hide Description OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Time Frame Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II who also had a response assessment
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed EGFRvIII and/or PTEN.
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Measure Type: Number
Unit of Measure: participants
Complete response 0 0
Partial response 0 0
Stable disease, >=8 weeks 5 4
Progressive disease, <8 weeks 5 8
Progressive disease 4 6
Unconfirmed partial response 4 4
35.Primary Outcome
Title Progression-free Survival at 6 Months
Hide Description Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used. The participants who are still alive and whose follow-up extends to at least 6 months are considered At Risk.
Time Frame Date of the first dose of study drug to 6 months
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All-treated Population for Phase II
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Measure Type: Number
Unit of Measure: participants
Disease progression at or prior to 6 months 15 16
Death at or prior to 6 months 0 2
Censored at or prior to 6 months 4 1
At risk beyond 6 months 0 3
36.Secondary Outcome
Title Phase I: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, the Time to Maximum Observed Concentration (Tmax) and C24 of Pazopanib and Lapatinib When Administered in Combination With EIAC.
Hide Description [Not Specified]
Time Frame Completed during first cycle of treatment.
Outcome Measure Data Not Reported
37.Secondary Outcome
Title Phase II: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, Tmax, and C24 of Pazopanib and Lapatinib, as Appropriate, When Administered Together in Combination With Non-EIAC.
Hide Description [Not Specified]
Time Frame Completed during first cycle of treatment.
Outcome Measure Data Not Reported
38.Secondary Outcome
Title Phase II: Plasma Concentrations of the Circulating Biomarkers VEGF, sVEGFR-1, and sVEGFR-2.
Hide Description [Not Specified]
Time Frame Completed during first cycle of treatment.
Outcome Measure Data Not Reported
39.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used.
Time Frame Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)
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Hide Analysis Population Description
All-treated Population for Phase II
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Measure Type: Number
Unit of Measure: participants
Disease progression 15 18
Death 0 2
Censored 4 2
40.Secondary Outcome
Title Time to Disease Progression or Death Due to Any Cause
Hide Description [Not Specified]
Time Frame Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Population for Phase II
Arm/Group Title Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description:
All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Overall Number of Participants Analyzed 19 22
Median (95% Confidence Interval)
Unit of Measure: days
62
(56 to 90)
56
(45 to 113)
Time Frame Serious adverse events (SAEs) and non-serious AES in Phases I and II were collected from Day 1 of study treatment to study completion (up to 844 days for Phase I; up to 878 days for Phase II).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Hide Arm/Group Description Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort. All participants received pazopanib 400 mg twice daily (QD) and lapatinib 1000 mg QD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN). All participants received pazopanib 400 mg QD and lapatinib 1000 mg QD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
All-Cause Mortality
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/34 (44.12%)   6/19 (31.58%)   8/22 (36.36%) 
Blood and lymphatic system disorders       
Thrombocytopenia  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Endocrine disorders       
Hypothyroidism  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Gastrointestinal disorders       
Vomiting  1  3/34 (8.82%)  0/19 (0.00%)  0/22 (0.00%) 
Nausea  1  2/34 (5.88%)  0/19 (0.00%)  0/22 (0.00%) 
Pancreatitis  1  0/34 (0.00%)  2/19 (10.53%)  0/22 (0.00%) 
Abdominal pain  1  0/34 (0.00%)  0/19 (0.00%)  1/22 (4.55%) 
Diarrhea  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
General disorders       
Fatigue  1  2/34 (5.88%)  0/19 (0.00%)  1/22 (4.55%) 
Pyrexia  1  2/34 (5.88%)  0/19 (0.00%)  0/22 (0.00%) 
Asthenia  1  0/34 (0.00%)  0/19 (0.00%)  1/22 (4.55%) 
Infections and infestations       
Infection  1  0/34 (0.00%)  0/19 (0.00%)  1/22 (4.55%) 
Pneumonia  1  0/34 (0.00%)  0/19 (0.00%)  1/22 (4.55%) 
Lobar pneumonia  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Pneumonia streptococcal  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Injury, poisoning and procedural complications       
Brain herniation  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Femoral neck fracture  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Pubis fracture  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  1/34 (2.94%)  0/19 (0.00%)  1/22 (4.55%) 
Aspartate aminotransferase increased  1  1/34 (2.94%)  0/19 (0.00%)  1/22 (4.55%) 
Transaminases increased  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Metabolism and nutrition disorders       
Hyperglycemia  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumor hemorrhage  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Nervous system disorders       
Convulsion  1  1/34 (2.94%)  1/19 (5.26%)  4/22 (18.18%) 
Cerebral hemorrhage  1  0/34 (0.00%)  0/19 (0.00%)  1/22 (4.55%) 
Partial seizures  1  0/34 (0.00%)  0/19 (0.00%)  1/22 (4.55%) 
Speech disorder  1  0/34 (0.00%)  1/19 (5.26%)  0/22 (0.00%) 
Headache  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Hemiparesis  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Syncope  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Psychiatric disorders       
Confusional state  1  2/34 (5.88%)  1/19 (5.26%)  0/22 (0.00%) 
Mental status changes  1  0/34 (0.00%)  1/19 (5.26%)  0/22 (0.00%) 
Mood altered  1  0/34 (0.00%)  1/19 (5.26%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Pneumonitis  1  0/34 (0.00%)  1/19 (5.26%)  0/22 (0.00%) 
Aspiration  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Dyspnea  1  1/34 (2.94%)  0/19 (0.00%)  0/22 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  0/34 (0.00%)  0/19 (0.00%)  1/22 (4.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Phase II: Biomarker Positive Phase II: Biomarker Negative
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/34 (97.06%)   18/19 (94.74%)   22/22 (100.00%) 
Blood and lymphatic system disorders       
Lymphopenia  1  3/34 (8.82%)  5/19 (26.32%)  6/22 (27.27%) 
Anemia  1  3/34 (8.82%)  1/19 (5.26%)  4/22 (18.18%) 
Thrombocytopenia  1  4/34 (11.76%)  1/19 (5.26%)  2/22 (9.09%) 
Leukopenia  1  1/34 (2.94%)  1/19 (5.26%)  3/22 (13.64%) 
Neutropenia  1  4/34 (11.76%)  0/19 (0.00%)  1/22 (4.55%) 
Cardiac disorders       
Sinus bradycardia  1  0/34 (0.00%)  0/19 (0.00%)  2/22 (9.09%) 
Ear and labyrinth disorders       
Deafness unilateral  1  2/34 (5.88%)  0/19 (0.00%)  1/22 (4.55%) 
Tinnitus  1  2/34 (5.88%)  0/19 (0.00%)  1/22 (4.55%) 
Endocrine disorders       
Cushingoid  1  0/34 (0.00%)  2/19 (10.53%)  2/22 (9.09%) 
Eye disorders       
Vision blurred  1  9/34 (26.47%)  1/19 (5.26%)  5/22 (22.73%) 
Gastrointestinal disorders       
Diarrhea  1  19/34 (55.88%)  12/19 (63.16%)  14/22 (63.64%) 
Nausea  1  9/34 (26.47%)  5/19 (26.32%)  3/22 (13.64%) 
Vomiting  1  2/34 (5.88%)  2/19 (10.53%)  3/22 (13.64%) 
Constipation  1  4/34 (11.76%)  1/19 (5.26%)  4/22 (18.18%) 
Abdominal pain  1  1/34 (2.94%)  1/19 (5.26%)  2/22 (9.09%) 
Hemorrhoidal hemorrhage  1  2/34 (5.88%)  0/19 (0.00%)  0/22 (0.00%) 
Flatulence  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Oral pain  1  0/34 (0.00%)  0/19 (0.00%)  2/22 (9.09%) 
General disorders       
Fatigue  1  16/34 (47.06%)  11/19 (57.89%)  10/22 (45.45%) 
Mucosal inflammation  1  3/34 (8.82%)  1/19 (5.26%)  1/22 (4.55%) 
Edema peripheral  1  3/34 (8.82%)  1/19 (5.26%)  2/22 (9.09%) 
Pyrexia  1  0/34 (0.00%)  0/19 (0.00%)  2/22 (9.09%) 
Asthenia  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Gait disturbance  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Hepatobiliary disorders       
Hyperbilirubinaemia/blood bilirubin increased  1  1/34 (2.94%)  1/19 (5.26%)  5/22 (22.73%) 
Infections and infestations       
Urinary tract infection  1  2/34 (5.88%)  0/19 (0.00%)  1/22 (4.55%) 
Candidiasis  1  1/34 (2.94%)  1/19 (5.26%)  1/22 (4.55%) 
Injury, poisoning and procedural complications       
Contusion  1  1/34 (2.94%)  0/19 (0.00%)  3/22 (13.64%) 
Investigations       
Alanine aminotransferase increased  1  8/34 (23.53%)  2/19 (10.53%)  2/22 (9.09%) 
Lipase increased  1  3/34 (8.82%)  2/19 (10.53%)  3/22 (13.64%) 
Blood amylase increased  1  1/34 (2.94%)  3/19 (15.79%)  2/22 (9.09%) 
Blood lactate dehydrogenase increased  1  1/34 (2.94%)  1/19 (5.26%)  3/22 (13.64%) 
Aspartate aminotransferase increased  1  4/34 (11.76%)  2/19 (10.53%)  1/22 (4.55%) 
Neutrophil count decreased  1  0/34 (0.00%)  2/19 (10.53%)  2/22 (9.09%) 
Blood alkaline phosphatase increased  1  2/34 (5.88%)  1/19 (5.26%)  0/22 (0.00%) 
White blood cell count decreased  1  2/34 (5.88%)  0/19 (0.00%)  0/22 (0.00%) 
Blood urea increased  1  1/34 (2.94%)  0/19 (0.00%)  3/22 (13.64%) 
Weight decreased  1  1/34 (2.94%)  2/19 (10.53%)  1/22 (4.55%) 
Weight increased  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Metabolism and nutrition disorders       
Hyperglycemia  1  2/34 (5.88%)  3/19 (15.79%)  6/22 (27.27%) 
Hypomagnesemia  1  1/34 (2.94%)  0/19 (0.00%)  4/22 (18.18%) 
Decreased appetitie  1  3/34 (8.82%)  2/19 (10.53%)  1/22 (4.55%) 
Dehydration  1  0/34 (0.00%)  0/19 (0.00%)  3/22 (13.64%) 
Hypoalbuminaemia  1  0/34 (0.00%)  1/19 (5.26%)  2/22 (9.09%) 
Hypocalcaemia  1  1/34 (2.94%)  1/19 (5.26%)  2/22 (9.09%) 
Hypokalaemia  1  0/34 (0.00%)  1/19 (5.26%)  2/22 (9.09%) 
Hypophosphataemia  1  0/34 (0.00%)  0/19 (0.00%)  3/22 (13.64%) 
Hyperkalaemia  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Hypoglycaemia  1  0/34 (0.00%)  0/19 (0.00%)  2/22 (9.09%) 
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  5/34 (14.71%)  0/19 (0.00%)  2/22 (9.09%) 
Arthralgia  1  3/34 (8.82%)  1/19 (5.26%)  1/22 (4.55%) 
Back pain  1  2/34 (5.88%)  2/19 (10.53%)  0/22 (0.00%) 
Joint stiffness  1  2/34 (5.88%)  0/19 (0.00%)  0/22 (0.00%) 
Musculoskeletal pain  1  0/34 (0.00%)  0/19 (0.00%)  3/22 (13.64%) 
Muscle spasms  1  0/34 (0.00%)  0/19 (0.00%)  2/22 (9.09%) 
Myalgia  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Pain in extremity  1  1/34 (2.94%)  1/19 (5.26%)  1/22 (4.55%) 
Nervous system disorders       
Headache  1  9/34 (26.47%)  7/19 (36.84%)  8/22 (36.36%) 
Convulsion  1  4/34 (11.76%)  2/19 (10.53%)  4/22 (18.18%) 
Peripheral sensory neuropathy  1  4/34 (11.76%)  3/19 (15.79%)  5/22 (22.73%) 
Somnolence  1  2/34 (5.88%)  2/19 (10.53%)  3/22 (13.64%) 
Speech disorder  1  1/34 (2.94%)  1/19 (5.26%)  3/22 (13.64%) 
Amnesia  1  4/34 (11.76%)  5/19 (26.32%)  1/22 (4.55%) 
Aphasia  1  4/34 (11.76%)  0/19 (0.00%)  0/22 (0.00%) 
Dizziness  1  0/34 (0.00%)  3/19 (15.79%)  1/22 (4.55%) 
Balance disorder  1  2/34 (5.88%)  0/19 (0.00%)  0/22 (0.00%) 
Cognitive disorder  1  2/34 (5.88%)  3/19 (15.79%)  4/22 (18.18%) 
Peripheral motor neuropathy  1  2/34 (5.88%)  3/19 (15.79%)  3/22 (13.64%) 
Pyramidal tract syndrome  1  2/34 (5.88%)  2/19 (10.53%)  1/22 (4.55%) 
Ataxia  1  1/34 (2.94%)  2/19 (10.53%)  4/22 (18.18%) 
Cranial nerve disorder  1  1/34 (2.94%)  0/19 (0.00%)  3/22 (13.64%) 
Dysgeusia  1  0/34 (0.00%)  2/19 (10.53%)  1/22 (4.55%) 
Hemiparesis  1  3/34 (8.82%)  1/19 (5.26%)  1/22 (4.55%) 
Memory impairment  1  1/34 (2.94%)  0/19 (0.00%)  2/22 (9.09%) 
Partial seizures  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Tremor  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Psychiatric disorders       
Confusional state  1  0/34 (0.00%)  4/19 (21.05%)  4/22 (18.18%) 
Mood altered/mood swings  1  1/34 (2.94%)  2/19 (10.53%)  1/22 (4.55%) 
Insomnia  1  4/34 (11.76%)  3/19 (15.79%)  3/22 (13.64%) 
Depressed mood  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Renal and urinary disorders       
Pollakiuria  1  2/34 (5.88%)  0/19 (0.00%)  0/22 (0.00%) 
Urinary incontinence  1  1/34 (2.94%)  0/19 (0.00%)  2/22 (9.09%) 
Reproductive system and breast disorders       
Sexual dysfunction  1  0/34 (0.00%)  2/19 (10.53%)  2/22 (9.09%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  3/34 (8.82%)  0/19 (0.00%)  4/22 (18.18%) 
Dyspnea  1  2/34 (5.88%)  0/19 (0.00%)  1/22 (4.55%) 
Oropharyngeal pain  1  2/34 (5.88%)  0/19 (0.00%)  1/22 (4.55%) 
Epistaxis  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Skin and subcutaneous tissue disorders       
Rash  1  5/34 (14.71%)  8/19 (42.11%)  4/22 (18.18%) 
Dermatitis acneiform  1  3/34 (8.82%)  1/19 (5.26%)  5/22 (22.73%) 
Alopecia  1  1/34 (2.94%)  0/19 (0.00%)  2/22 (9.09%) 
Exfoliative rash  1  1/34 (2.94%)  0/19 (0.00%)  2/22 (9.09%) 
Hair color changes  1  0/34 (0.00%)  1/19 (5.26%)  1/22 (4.55%) 
Vascular disorders       
Hypertension  1  9/34 (26.47%)  3/19 (15.79%)  9/22 (40.91%) 
Deep vein thrombosis  1  3/34 (8.82%)  0/19 (0.00%)  0/22 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00350727     History of Changes
Obsolete Identifiers: NCT00412711
Other Study ID Numbers: VEG102857
First Submitted: July 10, 2006
First Posted: July 11, 2006
Results First Submitted: December 26, 2010
Results First Posted: June 20, 2011
Last Update Posted: April 19, 2013