Trial Outcomes & Findings for Pazopanib In Combination With Lapatinib In Adult Patients With Relapsed Malignant Glioma (NCT NCT00350727)
NCT ID: NCT00350727
Last Updated: 2013-04-19
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
75 participants
Primary outcome timeframe
Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Results posted on
2013-04-19
Participant Flow
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.
Participant milestones
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
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.
|
Phase II: Biomarker Positive
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).
|
Phase II: Biomarker Negative
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.
|
|---|---|---|---|
|
Phase I: Dose Escalation
STARTED
|
34
|
0
|
0
|
|
Phase I: Dose Escalation
COMPLETED
|
0
|
0
|
0
|
|
Phase I: Dose Escalation
NOT COMPLETED
|
34
|
0
|
0
|
|
Phase II
STARTED
|
0
|
19
|
22
|
|
Phase II
COMPLETED
|
0
|
0
|
0
|
|
Phase II
NOT COMPLETED
|
0
|
19
|
22
|
Reasons for withdrawal
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
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.
|
Phase II: Biomarker Positive
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).
|
Phase II: Biomarker Negative
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.
|
|---|---|---|---|
|
Phase I: Dose Escalation
Adverse Event
|
4
|
0
|
0
|
|
Phase I: Dose Escalation
Lack of Efficacy
|
25
|
0
|
0
|
|
Phase I: Dose Escalation
Death
|
1
|
0
|
0
|
|
Phase I: Dose Escalation
Physician Decision
|
1
|
0
|
0
|
|
Phase I: Dose Escalation
Transition to Extension Phase
|
3
|
0
|
0
|
|
Phase II
Disease Progression
|
0
|
15
|
16
|
|
Phase II
Clinical Deterioration
|
0
|
1
|
0
|
|
Phase II
Withdrawal by Subject
|
0
|
2
|
1
|
|
Phase II
Adverse Event
|
0
|
1
|
1
|
|
Phase II
Death
|
0
|
0
|
2
|
|
Phase II
Sponsor Terminated Study
|
0
|
0
|
1
|
|
Phase II
Enrolled in Rollover Study
|
0
|
0
|
1
|
Baseline Characteristics
Pazopanib In Combination With Lapatinib In Adult Patients With Relapsed Malignant Glioma
Baseline characteristics by cohort
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=34 Participants
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.
|
Phase II: Biomarker Positive
n=19 Participants
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).
|
Phase II: Biomarker Negative
n=22 Participants
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
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
20-29 years old
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Age, Customized
30-39 years old
|
8 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
11 participants
n=4 Participants
|
|
Age, Customized
40-49 years old
|
11 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
23 participants
n=4 Participants
|
|
Age, Customized
50-59 years old
|
10 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
23 participants
n=4 Participants
|
|
Age, Customized
60-69 years old
|
3 participants
n=5 Participants
|
7 participants
n=7 Participants
|
2 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Age, Customized
>=70 years old
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
54 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian/European Heritage
|
34 participants
n=5 Participants
|
19 participants
n=7 Participants
|
21 participants
n=5 Participants
|
74 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)Population: 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.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=33 Participants
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.
|
Phase II: Biomarker Positive
n=19 Participants
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).
|
Phase II: Biomarker Negative
n=22 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
BL, 90-<140 mmHg; shift to post-BL, 90-<140 mmgHg
|
21 participants
|
12 participants
|
11 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
BL, 90-<140 mmHg; shift to post-BL, 140-<170 mmHg
|
12 participants
|
3 participants
|
8 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
BL, 90-<140 mmHg; shift to post-BL, >=170 mmHg
|
0 participants
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
BL, 140-<170 mmHg; shift to post-BL, 90-<140 mmHg
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
BL, 140-<170 mmHg; shift to post-BL, 140-<170 mmHg
|
0 participants
|
2 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
BL, 140-<170 mmHg; shift to post-BL, >=170 mmHg
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
BL, >=170 mmHg; shift to post-BL, 140-<170 mmHg
|
0 participants
|
1 participants
|
1 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)Population: 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.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=33 Participants
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.
|
Phase II: Biomarker Positive
n=19 Participants
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).
|
Phase II: Biomarker Negative
n=22 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
BL, 50-<90 mmHg; shift to post-BL, 50-<90 mmHg
|
23 participants
|
13 participants
|
9 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
BL, 50-<90 mmHg; shift to post-BL, 90-<110 mmHg
|
9 participants
|
4 participants
|
10 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
BL, 90-<110 mmHg; shift to post-BL, 50-<90 mmHg
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
BL, 90-<110 mmHg; shift to post-BL, 90-<110 mmHg
|
1 participants
|
0 participants
|
2 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
BL, 90-<110 mmHg; shift to post-BL, >=110 mmHg
|
0 participants
|
1 participants
|
1 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)Population: 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.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=33 Participants
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.
|
Phase II: Biomarker Positive
n=19 Participants
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).
|
Phase II: Biomarker Negative
n=22 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
BL, 44-100 bpm; shift to post-BL, 44-100 bpm
|
31 participants
|
14 participants
|
19 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
BL, 44-100 bpm; shift to post-BL, 101-120 bpm
|
0 participants
|
3 participants
|
2 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
BL, 101-120 bpm; shift to post-BL, 101-120 bpm
|
2 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
BL, 101-120 bpm; shift to post-BL, >120 bpm
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
BL, >120 bpm; shift to post-BL, 44-100 bpm
|
0 participants
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
BL, missing; shift to post-BL, 44-100 bpm
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=21 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin
|
-5.9 grams per liter (g/L)
Standard Deviation 9.57
|
-6.7 grams per liter (g/L)
Standard Deviation 9.95
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Alkaline phosphatase, n=19, 21
|
18.6 International Units per Liter (IU/L)
Standard Deviation 54.02
|
33.9 International Units per Liter (IU/L)
Standard Deviation 109.99
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Alanine aminotransferase, n=19, 22
|
56.1 International Units per Liter (IU/L)
Standard Deviation 131.99
|
132.7 International Units per Liter (IU/L)
Standard Deviation 393.89
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Aspartate aminotransferase, n=19, 22
|
36.4 International Units per Liter (IU/L)
Standard Deviation 88.50
|
52.7 International Units per Liter (IU/L)
Standard Deviation 178.02
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Lactate dehydrogenase, n=18, 19
|
291.50 International Units per Liter (IU/L)
Standard Deviation 443.725
|
171.63 International Units per Liter (IU/L)
Standard Deviation 606.986
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=19 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase
Amylase
|
22.72 Units per liter (U/L)
Standard Deviation 28.060
|
20.05 Units per liter (U/L)
Standard Deviation 30.288
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase
Lipase
|
131.4 Units per liter (U/L)
Standard Deviation 318.13
|
120.5 Units per liter (U/L)
Standard Deviation 163.51
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=21 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine
Total bilirubin
|
6.174 micromoles per liter (µmol/l)
Standard Deviation 7.2714
|
23.562 micromoles per liter (µmol/l)
Standard Deviation 71.1671
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine
Creatinine
|
6.93 micromoles per liter (µmol/l)
Standard Deviation 10.444
|
9.59 micromoles per liter (µmol/l)
Standard Deviation 14.852
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=21 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Calcium, n=19, 21
|
0.004 millimoles per liter (mmol/l)
Standard Deviation 0.1257
|
0.019 millimoles per liter (mmol/l)
Standard Deviation 0.0952
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Glucose, n=19, 21
|
0.082 millimoles per liter (mmol/l)
Standard Deviation 4.1342
|
1.850 millimoles per liter (mmol/l)
Standard Deviation 2.7180
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Potassium, n=19, 21
|
0.17 millimoles per liter (mmol/l)
Standard Deviation 0.471
|
0.30 millimoles per liter (mmol/l)
Standard Deviation 0.264
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Magnesium, n=19, 19
|
0.022 millimoles per liter (mmol/l)
Standard Deviation 0.0676
|
0.040 millimoles per liter (mmol/l)
Standard Deviation 0.0853
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Sodium, n=19, 21
|
1.7 millimoles per liter (mmol/l)
Standard Deviation 2.96
|
1.3 millimoles per liter (mmol/l)
Standard Deviation 1.85
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Urea, n=19, 21
|
0.770 millimoles per liter (mmol/l)
Standard Deviation 1.6840
|
1.071 millimoles per liter (mmol/l)
Standard Deviation 2.1736
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Inorganic phosphorus, n=19, 20
|
0.090 millimoles per liter (mmol/l)
Standard Deviation 0.2352
|
0.076 millimoles per liter (mmol/l)
Standard Deviation 0.2048
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=16 Participants
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.
|
Phase II: Biomarker Positive
n=13 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine)
Thyroxine, n=16, 13
|
-8.052 picomoles per liter (pmol/l)
Standard Deviation 30.2175
|
10.806 picomoles per liter (pmol/l)
Standard Deviation 40.5626
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine)
Free T3, n=4, 4
|
0.420 picomoles per liter (pmol/l)
Standard Deviation 0.5010
|
-2.442 picomoles per liter (pmol/l)
Standard Deviation 2.3525
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=18 Participants
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.
|
Phase II: Biomarker Positive
n=20 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone
|
1.37 milliunits per liter (mU/L)
Standard Deviation 2.106
|
2.59 milliunits per liter (mU/L)
Standard Deviation 4.377
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=13 Participants
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.
|
Phase II: Biomarker Positive
n=8 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3
|
-0.181 nanomoles per liter (nmol/l)
Standard Deviation 0.6521
|
-0.104 nanomoles per liter (nmol/l)
Standard Deviation 0.3516
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin
|
-4.6 grams per liter (g/L)
Standard Deviation 11.25
|
-8.0 grams per liter (g/L)
Standard Deviation 16.75
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit
|
-0.016 percent
Standard Deviation 0.0320
|
-0.027 percent
Standard Deviation 0.0452
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Lymphocytes, n=16, 19
|
-0.26 giga (10^9) per liter (GI/L)
Standard Deviation 0.556
|
-0.21 giga (10^9) per liter (GI/L)
Standard Deviation 0.573
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Total Neutrophils, n=16, 18
|
-2.87 giga (10^9) per liter (GI/L)
Standard Deviation 3.021
|
-4.72 giga (10^9) per liter (GI/L)
Standard Deviation 5.067
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Platelet count, n=19, 22
|
-58.7 giga (10^9) per liter (GI/L)
Standard Deviation 53.98
|
-55.7 giga (10^9) per liter (GI/L)
Standard Deviation 59.79
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
White blood cells, n=19, 22
|
-2.63 giga (10^9) per liter (GI/L)
Standard Deviation 2.934
|
-4.06 giga (10^9) per liter (GI/L)
Standard Deviation 6.026
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time)
|
0.030 ratio
Standard Deviation 0.0663
|
0.042 ratio
Standard Deviation 0.1094
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 878 days for Phase II)Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time
Partial thromboplastin time
|
2.10 seconds (sec)
Standard Deviation 1.985
|
2.62 seconds (sec)
Standard Deviation 3.175
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time
Prothrombin time
|
0.0 seconds (sec)
Standard Deviation 0.57
|
0.2 seconds (sec)
Standard Deviation 1.19
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin
|
-4.25 grams per liter (g/L)
Standard Deviation 4.573
|
-6.17 grams per liter (g/L)
Standard Deviation 5.707
|
-3.80 grams per liter (g/L)
Standard Deviation 1.924
|
-5.17 grams per liter (g/L)
Standard Deviation 3.545
|
-13.66 grams per liter (g/L)
Standard Deviation 16.959
|
-7.17 grams per liter (g/L)
Standard Deviation 4.215
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Alkaline phosphatase
|
9.8 International Units per Liter (IU/L)
Standard Deviation 11.47
|
22.8 International Units per Liter (IU/L)
Standard Deviation 39.55
|
31.2 International Units per Liter (IU/L)
Standard Deviation 53.60
|
15.8 International Units per Liter (IU/L)
Standard Deviation 22.66
|
22.0 International Units per Liter (IU/L)
Standard Deviation 28.54
|
22.0 International Units per Liter (IU/L)
Standard Deviation 47.15
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Alanine aminotransferase
|
36.8 International Units per Liter (IU/L)
Standard Deviation 66.35
|
139.5 International Units per Liter (IU/L)
Standard Deviation 204.81
|
47.0 International Units per Liter (IU/L)
Standard Deviation 48.09
|
33.2 International Units per Liter (IU/L)
Standard Deviation 25.25
|
4.8 International Units per Liter (IU/L)
Standard Deviation 7.19
|
47.7 International Units per Liter (IU/L)
Standard Deviation 56.43
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Aspartate aminotransferase
|
15.0 International Units per Liter (IU/L)
Standard Deviation 31.72
|
49.3 International Units per Liter (IU/L)
Standard Deviation 71.63
|
13.8 International Units per Liter (IU/L)
Standard Deviation 15.71
|
8.8 International Units per Liter (IU/L)
Standard Deviation 7.03
|
13.5 International Units per Liter (IU/L)
Standard Deviation 16.20
|
19.3 International Units per Liter (IU/L)
Standard Deviation 18.47
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Lactate dehydrogenase
|
148.0 International Units per Liter (IU/L)
Standard Deviation 96.42
|
127.0 International Units per Liter (IU/L)
Standard Deviation 144.60
|
46.0 International Units per Liter (IU/L)
Standard Deviation 35.86
|
321.2 International Units per Liter (IU/L)
Standard Deviation 534.42
|
124.7 International Units per Liter (IU/L)
Standard Deviation 136.46
|
116.8 International Units per Liter (IU/L)
Standard Deviation 59.26
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase
Amylase
|
24.3 Units per liter (U/L)
Standard Deviation 36.42
|
24.4 Units per liter (U/L)
Standard Deviation 17.04
|
27.3 Units per liter (U/L)
Standard Deviation 66.4
|
31.0 Units per liter (U/L)
Standard Deviation 38.96
|
44.4 Units per liter (U/L)
Standard Deviation 52.52
|
23.3 Units per liter (U/L)
Standard Deviation 39.38
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase
Lipase
|
147.0 Units per liter (U/L)
Standard Deviation 292.02
|
23.3 Units per liter (U/L)
Standard Deviation 44.98
|
33.0 Units per liter (U/L)
Standard Deviation 56.79
|
151.8 Units per liter (U/L)
Standard Deviation 230.63
|
67.3 Units per liter (U/L)
Standard Deviation 101.83
|
7.8 Units per liter (U/L)
Standard Deviation 21.09
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine
Creatinine
|
4.420 micromoles per liter (µmol/l)
Standard Deviation 15.3113
|
8.367 micromoles per liter (µmol/l)
Standard Deviation 11.3656
|
7.336 micromoles per liter (µmol/l)
Standard Deviation 6.6049
|
6.893 micromoles per liter (µmol/l)
Standard Deviation 6.6297
|
9.727 micromoles per liter (µmol/l)
Standard Deviation 9.7448
|
12.005 micromoles per liter (µmol/l)
Standard Deviation 19.3179
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine
Total bilirubin
|
-0.000 micromoles per liter (µmol/l)
Standard Deviation 4.6307
|
2.613 micromoles per liter (µmol/l)
Standard Deviation 2.5162
|
3.368 micromoles per liter (µmol/l)
Standard Deviation 2.1520
|
6.130 micromoles per liter (µmol/l)
Standard Deviation 6.0799
|
4.135 micromoles per liter (µmol/l)
Standard Deviation 3.8089
|
6.398 micromoles per liter (µmol/l)
Standard Deviation 3.8952
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Calcium
|
-0.062 millimoles per liter (mmol/l)
Standard Deviation 0.0250
|
-0.045 millimoles per liter (mmol/l)
Standard Deviation 0.1173
|
0.036 millimoles per liter (mmol/l)
Standard Deviation 0.0572
|
0.061 millimoles per liter (mmol/l)
Standard Deviation 0.0874
|
0.047 millimoles per liter (mmol/l)
Standard Deviation 0.1155
|
-0.014 millimoles per liter (mmol/l)
Standard Deviation 0.1166
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Glucose
|
0.56 millimoles per liter (mmol/l)
Standard Deviation 1.385
|
3.35 millimoles per liter (mmol/l)
Standard Deviation 6.653
|
1.20 millimoles per liter (mmol/l)
Standard Deviation 1.114
|
1.02 millimoles per liter (mmol/l)
Standard Deviation 2.654
|
1.55 millimoles per liter (mmol/l)
Standard Deviation 0.589
|
0.65 millimoles per liter (mmol/l)
Standard Deviation 0.934
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Potassium
|
0.075 millimoles per liter (mmol/l)
Standard Deviation 0.4992
|
0.400 millimoles per liter (mmol/l)
Standard Deviation 0.3033
|
0.420 millimoles per liter (mmol/l)
Standard Deviation 0.3033
|
0.500 millimoles per liter (mmol/l)
Standard Deviation 0.2608
|
0.600 millimoles per liter (mmol/l)
Standard Deviation 0.5967
|
0.183 millimoles per liter (mmol/l)
Standard Deviation 0.2229
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Magnesium
|
0.069 millimoles per liter (mmol/l)
Standard Deviation 0.0237
|
-0.019 millimoles per liter (mmol/l)
Standard Deviation 0.0573
|
0.058 millimoles per liter (mmol/l)
Standard Deviation 0.0463
|
0.051 millimoles per liter (mmol/l)
Standard Deviation 0.0510
|
0.043 millimoles per liter (mmol/l)
Standard Deviation 0.0615
|
0.056 millimoles per liter (mmol/l)
Standard Deviation 0.0920
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Sodium
|
-1.000 millimoles per liter (mmol/l)
Standard Deviation 1.8257
|
0.500 millimoles per liter (mmol/l)
Standard Deviation 2.0736
|
1.800 millimoles per liter (mmol/l)
Standard Deviation 1.6432
|
1.333 millimoles per liter (mmol/l)
Standard Deviation 2.0656
|
1.500 millimoles per liter (mmol/l)
Standard Deviation 4.5497
|
0.000 millimoles per liter (mmol/l)
Standard Deviation 0.6325
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Urea
|
1.9 millimoles per liter (mmol/l)
Standard Deviation 0.18
|
0.6 millimoles per liter (mmol/l)
Standard Deviation 1.18
|
0.8 millimoles per liter (mmol/l)
Standard Deviation 1.74
|
1.1 millimoles per liter (mmol/l)
Standard Deviation 1.27
|
0.9 millimoles per liter (mmol/l)
Standard Deviation 1.20
|
1.7 millimoles per liter (mmol/l)
Standard Deviation 1.72
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Inorganic phosphorus
|
0.02 millimoles per liter (mmol/l)
Standard Deviation 0.168
|
0.11 millimoles per liter (mmol/l)
Standard Deviation 0.186
|
0.41 millimoles per liter (mmol/l)
Standard Deviation 0.553
|
0.16 millimoles per liter (mmol/l)
Standard Deviation 0.164
|
0.01 millimoles per liter (mmol/l)
Standard Deviation 0.129
|
0.25 millimoles per liter (mmol/l)
Standard Deviation 0.185
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine
|
-0.740 picomoles per liter (pmol/l)
Standard Deviation 2.8496
|
-1.498 picomoles per liter (pmol/l)
Standard Deviation 1.8681
|
1.105 picomoles per liter (pmol/l)
Standard Deviation 3.6173
|
1.879 picomoles per liter (pmol/l)
Standard Deviation 2.8191
|
0.377 picomoles per liter (pmol/l)
Standard Deviation 3.9731
|
-0.781 picomoles per liter (pmol/l)
Standard Deviation 1.0040
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: 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.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
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.
|
Phase II: Biomarker Positive
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine)
|
—
|
—
|
-0.07 picomoles per liter (pmol/l)
Standard Deviation 0.222
|
—
|
-0.94 picomoles per liter (pmol/l)
Standard Deviation 1.291
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone
|
-0.5068 milliunits per liter (mU/L)
Standard Deviation 1.99588
|
0.1900 milliunits per liter (mU/L)
Standard Deviation 0.38931
|
0.6543 milliunits per liter (mU/L)
Standard Deviation 0.73309
|
0.6660 milliunits per liter (mU/L)
Standard Deviation 0.70497
|
0.6080 milliunits per liter (mU/L)
Standard Deviation 11.10117
|
2.2940 milliunits per liter (mU/L)
Standard Deviation 1.25335
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: 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.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3
|
-0.071 nanomoles per liter (nmol/l)
Standard Deviation 0.1113
|
0.214 nanomoles per liter (nmol/l)
Standard Deviation 0.2851
|
—
|
0.004 nanomoles per liter (nmol/l)
Standard Deviation 0.0028
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin
|
-7.25 grams per Liter (g/L)
Standard Deviation 14.975
|
-7.83 grams per Liter (g/L)
Standard Deviation 12.999
|
-4.80 grams per Liter (g/L)
Standard Deviation 9.834
|
-3.33 grams per Liter (g/L)
Standard Deviation 13.095
|
-16.17 grams per Liter (g/L)
Standard Deviation 9.867
|
-21.02 grams per Liter (g/L)
Standard Deviation 59.642
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit
|
-0.02 percent
Standard Deviation 0.034
|
-0.02 percent
Standard Deviation 0.029
|
-0.02 percent
Standard Deviation 0.023
|
0.00 percent
Standard Deviation 0.027
|
-0.09 percent
Standard Deviation 0.103
|
0.01 percent
Standard Deviation 0.024
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Platelet count, n=4, 6, 5, 6, 6, 6
|
-12.3 giga (10^9) per liter (GI/L)
Standard Deviation 30.08
|
-74.7 giga (10^9) per liter (GI/L)
Standard Deviation 74.18
|
-65.4 giga (10^9) per liter (GI/L)
Standard Deviation 32.65
|
-25.3 giga (10^9) per liter (GI/L)
Standard Deviation 40.00
|
-35.5 giga (10^9) per liter (GI/L)
Standard Deviation 54.72
|
-61.8 giga (10^9) per liter (GI/L)
Standard Deviation 32.17
|
|
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
White blood cell count, n=4, 6, 5, 6, 6, 6
|
-0.845 giga (10^9) per liter (GI/L)
Standard Deviation 1.0849
|
-2.933 giga (10^9) per liter (GI/L)
Standard Deviation 3.6335
|
-1.950 giga (10^9) per liter (GI/L)
Standard Deviation 2.1249
|
-0.850 giga (10^9) per liter (GI/L)
Standard Deviation 0.9072
|
-1.717 giga (10^9) per liter (GI/L)
Standard Deviation 2.2355
|
-0.850 giga (10^9) per liter (GI/L)
Standard Deviation 2.4468
|
|
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Lymphocytes, n=3, 6, 4, 6, 6, 6
|
-0.377 giga (10^9) per liter (GI/L)
Standard Deviation 0.4611
|
-0.120 giga (10^9) per liter (GI/L)
Standard Deviation 0.4291
|
-0.153 giga (10^9) per liter (GI/L)
Standard Deviation 0.3083
|
-0.032 giga (10^9) per liter (GI/L)
Standard Deviation 0.2807
|
-0.218 giga (10^9) per liter (GI/L)
Standard Deviation 0.2316
|
-0.250 giga (10^9) per liter (GI/L)
Standard Deviation 0.3017
|
|
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Total Neutrophils, n=3, 6, 4, 6, 6, 6
|
-0.693 giga (10^9) per liter (GI/L)
Standard Deviation 1.0775
|
-3.000 giga (10^9) per liter (GI/L)
Standard Deviation 3.2727
|
-1.370 giga (10^9) per liter (GI/L)
Standard Deviation 1.5036
|
-0.595 giga (10^9) per liter (GI/L)
Standard Deviation 0.8783
|
-1.723 giga (10^9) per liter (GI/L)
Standard Deviation 1.7320
|
-0.617 giga (10^9) per liter (GI/L)
Standard Deviation 2.7154
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: 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.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=5 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time)
|
0.077 ratio
Standard Deviation 0.0866
|
-0.023 ratio
Standard Deviation 0.0638
|
0.056 ratio
Standard Deviation 0.0472
|
0.000 ratio
Standard Deviation 0.1097
|
0.015 ratio
Standard Deviation 0.0764
|
0.006 ratio
Standard Deviation 0.0134
|
PRIMARY outcome
Timeframe: Baseline to study completion (up to 844 days for Phase I)Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=5 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time
Partial thromboplastin time
|
1.10 seconds (sec)
Standard Deviation 1.299
|
2.88 seconds (sec)
Standard Deviation 1.986
|
2.62 seconds (sec)
Standard Deviation 5.545
|
-0.38 seconds (sec)
Standard Deviation 6.122
|
2.18 seconds (sec)
Standard Deviation 2.082
|
1.00 seconds (sec)
Standard Deviation 1.093
|
|
Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time
Prothrombin time
|
0.38 seconds (sec)
Standard Deviation 0.532
|
0.47 seconds (sec)
Standard Deviation 0.940
|
0.64 seconds (sec)
Standard Deviation 0.981
|
-0.02 seconds (sec)
Standard Deviation 0.796
|
1.07 seconds (sec)
Standard Deviation 1.722
|
0.56 seconds (sec)
Standard Deviation 0.885
|
PRIMARY outcome
Timeframe: Cycle 1 in Phase I (up to Day 28)Population: All-treated Population for Phase I
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=4 Participants
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.
|
Phase II: Biomarker Positive
n=6 Participants
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).
|
Phase II: Biomarker Negative
n=5 Participants
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
n=7 Participants
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
n=6 Participants
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
1 participants
|
1 participants
|
PRIMARY outcome
Timeframe: 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)Population: All-treated Population in Phase II who also had a response assessment
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
Complete response
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
Partial response
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
Stable disease, >=8 weeks
|
7 participants
|
6 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
Progressive disease, <8 weeks
|
7 participants
|
8 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
Progressive disease
|
4 participants
|
6 participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 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)Population: All-treated Population for Phase II who also had a response assessment.
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
Complete response
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
Partial response
|
1 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
Stable disease, >=8 weeks
|
7 participants
|
7 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
Progressive disease, <8 weeks
|
7 participants
|
9 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
Progressive disease
|
4 participants
|
5 participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 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)Population: All-treated Population for Phase II who also had a response assessment
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Progressive disease
|
4 participants
|
6 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Complete response
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Partial response
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Stable disease, >=8 weeks
|
5 participants
|
4 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Progressive disease, <8 weeks
|
5 participants
|
8 participants
|
—
|
—
|
—
|
—
|
|
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Unconfirmed partial response
|
4 participants
|
4 participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Date of the first dose of study drug to 6 monthsPopulation: All-treated Population for Phase II
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Progression-free Survival at 6 Months
Disease progression at or prior to 6 months
|
15 participants
|
16 participants
|
—
|
—
|
—
|
—
|
|
Progression-free Survival at 6 Months
Death at or prior to 6 months
|
0 participants
|
2 participants
|
—
|
—
|
—
|
—
|
|
Progression-free Survival at 6 Months
Censored at or prior to 6 months
|
4 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Progression-free Survival at 6 Months
At risk beyond 6 months
|
0 participants
|
3 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Completed during first cycle of treatment.Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Completed during first cycle of treatment.Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Completed during first cycle of treatment.Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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)Population: All-treated Population for Phase II
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.
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Progression-free Survival
Disease progression
|
15 participants
|
18 participants
|
—
|
—
|
—
|
—
|
|
Progression-free Survival
Death
|
0 participants
|
2 participants
|
—
|
—
|
—
|
—
|
|
Progression-free Survival
Censored
|
4 participants
|
2 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: All-treated Population for Phase II
Outcome measures
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=19 Participants
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.
|
Phase II: Biomarker Positive
n=22 Participants
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).
|
Phase II: Biomarker Negative
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.
|
Phase I: Pazopanib 800 mg/Lapatinib 750 mg
Pazopanib 800 mg OD and Lapatinib 750 mg BID
|
Phase I: Pazopanib 800 mg/Lapatinib 1000 mg
Pazopanib 800 mg OD and Lapatinib 1000 mg BID
|
Phase I: Pazopanib 600 mg/Lapatinib 1000 mg
Pazopanib 600 mg BID and Lapatinib 1000 mg BID
|
|---|---|---|---|---|---|---|
|
Time to Disease Progression or Death Due to Any Cause
|
62 days
Interval 56.0 to 90.0
|
56 days
Interval 45.0 to 113.0
|
—
|
—
|
—
|
—
|
Adverse Events
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
Serious events: 15 serious events
Other events: 33 other events
Deaths: 0 deaths
Phase II: Biomarker Positive
Serious events: 6 serious events
Other events: 18 other events
Deaths: 0 deaths
Phase II: Biomarker Negative
Serious events: 8 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=34 participants at risk
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.
|
Phase II: Biomarker Positive
n=19 participants at risk
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).
|
Phase II: Biomarker Negative
n=22 participants at risk
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.
|
|---|---|---|---|
|
Nervous system disorders
Convulsion
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
18.2%
4/22 • 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).
|
|
Gastrointestinal disorders
Vomiting
|
8.8%
3/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
General disorders
Fatigue
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Psychiatric disorders
Confusional state
|
5.9%
2/34 • 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).
|
5.3%
1/19 • 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).
|
0.00%
0/22 • 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).
|
|
Gastrointestinal disorders
Nausea
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
General disorders
Pyrexia
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/34 • 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).
|
10.5%
2/19 • 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).
|
0.00%
0/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Investigations
Alanine aminotransferase increased
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Investigations
Aspartate aminotransferase increased
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Nervous system disorders
Cerebral hemorrhage
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Nervous system disorders
Partial seizures
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
0.00%
0/22 • 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).
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
0.00%
0/22 • 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).
|
|
Psychiatric disorders
Mood altered
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
0.00%
0/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
0.00%
0/22 • 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).
|
|
Infections and infestations
Infection
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Infections and infestations
Pneumonia
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
General disorders
Asthenia
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Gastrointestinal disorders
Diarrhea
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Nervous system disorders
Headache
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Nervous system disorders
Hemiparesis
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Nervous system disorders
Syncope
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Injury, poisoning and procedural complications
Brain herniation
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Investigations
Transaminases increased
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Endocrine disorders
Hypothyroidism
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Infections and infestations
Lobar pneumonia
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Infections and infestations
Pneumonia streptococcal
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor hemorrhage
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
Other adverse events
| Measure |
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg
n=34 participants at risk
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.
|
Phase II: Biomarker Positive
n=19 participants at risk
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).
|
Phase II: Biomarker Negative
n=22 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
55.9%
19/34 • 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).
|
63.2%
12/19 • 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).
|
63.6%
14/22 • 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).
|
|
General disorders
Fatigue
|
47.1%
16/34 • 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).
|
57.9%
11/19 • 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).
|
45.5%
10/22 • 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).
|
|
Nervous system disorders
Headache
|
26.5%
9/34 • 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).
|
36.8%
7/19 • 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).
|
36.4%
8/22 • 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).
|
|
Vascular disorders
Hypertension
|
26.5%
9/34 • 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).
|
15.8%
3/19 • 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).
|
40.9%
9/22 • 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).
|
|
Gastrointestinal disorders
Nausea
|
26.5%
9/34 • 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).
|
26.3%
5/19 • 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).
|
13.6%
3/22 • 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).
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.7%
5/34 • 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).
|
42.1%
8/19 • 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).
|
18.2%
4/22 • 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).
|
|
Eye disorders
Vision blurred
|
26.5%
9/34 • 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).
|
5.3%
1/19 • 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).
|
22.7%
5/22 • 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).
|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.8%
3/34 • 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).
|
26.3%
5/19 • 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).
|
27.3%
6/22 • 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).
|
|
Nervous system disorders
Convulsion
|
11.8%
4/34 • 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).
|
10.5%
2/19 • 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).
|
18.2%
4/22 • 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).
|
|
Investigations
Alanine aminotransferase increased
|
23.5%
8/34 • 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).
|
10.5%
2/19 • 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).
|
9.1%
2/22 • 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).
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.9%
2/34 • 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).
|
15.8%
3/19 • 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).
|
27.3%
6/22 • 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).
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/34 • 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).
|
21.1%
4/19 • 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).
|
18.2%
4/22 • 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).
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
11.8%
4/34 • 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).
|
15.8%
3/19 • 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).
|
22.7%
5/22 • 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).
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
2/34 • 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).
|
10.5%
2/19 • 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).
|
13.6%
3/22 • 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).
|
|
Gastrointestinal disorders
Constipation
|
11.8%
4/34 • 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).
|
5.3%
1/19 • 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).
|
18.2%
4/22 • 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).
|
|
Blood and lymphatic system disorders
Anemia
|
8.8%
3/34 • 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).
|
5.3%
1/19 • 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).
|
18.2%
4/22 • 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).
|
|
Investigations
Lipase increased
|
8.8%
3/34 • 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).
|
10.5%
2/19 • 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).
|
13.6%
3/22 • 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).
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
18.2%
4/22 • 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).
|
|
Nervous system disorders
Somnolence
|
5.9%
2/34 • 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).
|
10.5%
2/19 • 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).
|
13.6%
3/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.8%
3/34 • 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).
|
0.00%
0/19 • 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).
|
18.2%
4/22 • 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).
|
|
Investigations
Blood amylase increased
|
2.9%
1/34 • 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).
|
15.8%
3/19 • 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).
|
9.1%
2/22 • 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).
|
|
Hepatobiliary disorders
Hyperbilirubinaemia/blood bilirubin increased
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
22.7%
5/22 • 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).
|
|
Investigations
Blood lactate dehydrogenase increased
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
13.6%
3/22 • 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).
|
|
Nervous system disorders
Speech disorder
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
13.6%
3/22 • 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).
|
|
Gastrointestinal disorders
Abdominal pain
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
9.1%
2/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
14.7%
5/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.8%
4/34 • 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).
|
5.3%
1/19 • 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).
|
9.1%
2/22 • 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).
|
|
Investigations
Aspartate aminotransferase increased
|
11.8%
4/34 • 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).
|
10.5%
2/19 • 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).
|
4.5%
1/22 • 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).
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
13.6%
3/22 • 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).
|
|
Psychiatric disorders
Mood altered/mood swings
|
2.9%
1/34 • 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).
|
10.5%
2/19 • 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).
|
4.5%
1/22 • 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).
|
|
Psychiatric disorders
Insomnia
|
11.8%
4/34 • 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).
|
15.8%
3/19 • 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).
|
13.6%
3/22 • 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).
|
|
Nervous system disorders
Amnesia
|
11.8%
4/34 • 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).
|
26.3%
5/19 • 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).
|
4.5%
1/22 • 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).
|
|
Nervous system disorders
Aphasia
|
11.8%
4/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Blood and lymphatic system disorders
Neutropenia
|
11.8%
4/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/34 • 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).
|
10.5%
2/19 • 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).
|
9.1%
2/22 • 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).
|
|
Reproductive system and breast disorders
Sexual dysfunction
|
0.00%
0/34 • 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).
|
10.5%
2/19 • 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).
|
9.1%
2/22 • 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).
|
|
Endocrine disorders
Cushingoid
|
0.00%
0/34 • 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).
|
10.5%
2/19 • 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).
|
9.1%
2/22 • 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).
|
|
Nervous system disorders
Dizziness
|
0.00%
0/34 • 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).
|
15.8%
3/19 • 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).
|
4.5%
1/22 • 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).
|
|
General disorders
Mucosal inflammation
|
8.8%
3/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
General disorders
Edema peripheral
|
8.8%
3/34 • 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).
|
5.3%
1/19 • 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).
|
9.1%
2/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
8.8%
3/34 • 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).
|
5.3%
1/19 • 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).
|
22.7%
5/22 • 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).
|
|
Metabolism and nutrition disorders
Decreased appetitie
|
8.8%
3/34 • 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).
|
10.5%
2/19 • 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).
|
4.5%
1/22 • 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).
|
|
Vascular disorders
Deep vein thrombosis
|
8.8%
3/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.8%
3/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Nervous system disorders
Balance disorder
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Nervous system disorders
Cognitive disorder
|
5.9%
2/34 • 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).
|
15.8%
3/19 • 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).
|
18.2%
4/22 • 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).
|
|
Nervous system disorders
Peripheral motor neuropathy
|
5.9%
2/34 • 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).
|
15.8%
3/19 • 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).
|
13.6%
3/22 • 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).
|
|
Nervous system disorders
Pyramidal tract syndrome
|
5.9%
2/34 • 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).
|
10.5%
2/19 • 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).
|
4.5%
1/22 • 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).
|
|
General disorders
Pyrexia
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Investigations
Blood alkaline phosphatase increased
|
5.9%
2/34 • 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).
|
5.3%
1/19 • 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).
|
0.00%
0/22 • 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).
|
|
Investigations
White blood cell count decreased
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.9%
2/34 • 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).
|
10.5%
2/19 • 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).
|
0.00%
0/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Infections and infestations
Urinary tract infection
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Renal and urinary disorders
Pollakiuria
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
0.00%
0/22 • 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).
|
|
Ear and labyrinth disorders
Deafness unilateral
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Ear and labyrinth disorders
Tinnitus
|
5.9%
2/34 • 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).
|
0.00%
0/19 • 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).
|
4.5%
1/22 • 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).
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Nervous system disorders
Ataxia
|
2.9%
1/34 • 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).
|
10.5%
2/19 • 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).
|
18.2%
4/22 • 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).
|
|
Nervous system disorders
Cranial nerve disorder
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
13.6%
3/22 • 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).
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/34 • 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).
|
10.5%
2/19 • 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).
|
4.5%
1/22 • 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).
|
|
Nervous system disorders
Hemiparesis
|
8.8%
3/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Nervous system disorders
Memory impairment
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Nervous system disorders
Partial seizures
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Nervous system disorders
Tremor
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
General disorders
Asthenia
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
General disorders
Gait disturbance
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Skin and subcutaneous tissue disorders
Hair color changes
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
13.6%
3/22 • 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).
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
9.1%
2/22 • 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).
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
9.1%
2/22 • 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).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
9.1%
2/22 • 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).
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
13.6%
3/22 • 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).
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Investigations
Blood urea increased
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
13.6%
3/22 • 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).
|
|
Investigations
Weight decreased
|
2.9%
1/34 • 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).
|
10.5%
2/19 • 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).
|
4.5%
1/22 • 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).
|
|
Investigations
Weight increased
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
13.6%
3/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Infections and infestations
Candidiasis
|
2.9%
1/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Renal and urinary disorders
Urinary incontinence
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
9.1%
2/22 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/34 • 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).
|
5.3%
1/19 • 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).
|
4.5%
1/22 • 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).
|
|
Injury, poisoning and procedural complications
Contusion
|
2.9%
1/34 • 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).
|
0.00%
0/19 • 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).
|
13.6%
3/22 • 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).
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER