Trial Outcomes & Findings for Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Inflammatory Breast Cancer (NCT NCT00558103)
NCT ID: NCT00558103
Last Updated: 2013-02-04
Results Overview
RECIST-based response assessment was done at Weeks (Wks) 4 and 8 and every 8 weeks thereafter. Cutaneous disease assessment was done at Wk 4 and every 4 weeks thereafter. OR was evaluated when the skin and RECIST assessments coincided. Per RECIST, CR is the disappearance of all target and non-target lesions; PR is at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. Cutaneous disease contained non-measurable and measurable skin disease, which was assessed by skin assessment tools.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
163 participants
Primary outcome timeframe
Baseline until disease progression/recurrence was documented, assessed for up to 66 weeks
Results posted on
2013-02-04
Participant Flow
This study consisted of an initial randomized treatment phase; participants were randomized to receive lapatinib, pazopanib, or combination therapy. Participants who received pazopanib monotherapy in this initial phase and experienced disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
Enrollment in Cohort 1 was halted after 76 participants had been randomized based on safety data from Study VEG20007 (NCT00347919). The protocol was amended (Amendment 2) to change the combination therapy dose (Cohort 2); in addition, an open-label pazopanib arm (pazopanib 800 milligrams) was added (Cohort 2).
Participant milestones
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Open-label Lapatinib 1500 mg
Participants who received pazopanib 800 mg in the randomized treatment phase were given the option to receive oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) QD.
|
|---|---|---|---|---|---|---|
|
Randomized Treatment Phase
STARTED
|
38
|
38
|
36
|
13
|
38
|
0
|
|
Randomized Treatment Phase
COMPLETED
|
33
|
34
|
33
|
11
|
33
|
0
|
|
Randomized Treatment Phase
NOT COMPLETED
|
5
|
4
|
3
|
2
|
5
|
0
|
|
Monotherapy Extension Phase
STARTED
|
0
|
0
|
0
|
0
|
0
|
9
|
|
Monotherapy Extension Phase
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Monotherapy Extension Phase
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
9
|
Reasons for withdrawal
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Open-label Lapatinib 1500 mg
Participants who received pazopanib 800 mg in the randomized treatment phase were given the option to receive oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) QD.
|
|---|---|---|---|---|---|---|
|
Randomized Treatment Phase
Lost to Follow-up
|
2
|
2
|
2
|
1
|
3
|
0
|
|
Randomized Treatment Phase
Withdrawal by Subject
|
2
|
2
|
0
|
0
|
1
|
0
|
|
Randomized Treatment Phase
Disease Progression
|
1
|
0
|
1
|
0
|
0
|
0
|
|
Randomized Treatment Phase
Adverse Event
|
0
|
0
|
0
|
1
|
1
|
0
|
|
Monotherapy Extension Phase
Protocol Violation
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Monotherapy Extension Phase
Disease Progression
|
0
|
0
|
0
|
0
|
0
|
8
|
Baseline Characteristics
Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Inflammatory Breast Cancer
Baseline characteristics by cohort
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
n=38 Participants
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
n=38 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
n=36 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
n=13 Participants
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
n=38 Participants
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Total
n=163 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age Continuous
Years
|
51.9 Years
STANDARD_DEVIATION 9.00 • n=5 Participants
|
52.4 Years
STANDARD_DEVIATION 12.84 • n=7 Participants
|
53.0 Years
STANDARD_DEVIATION 10.39 • n=5 Participants
|
54.7 Years
STANDARD_DEVIATION 12.26 • n=4 Participants
|
53.9 Years
STANDARD_DEVIATION 12.65 • n=21 Participants
|
53.0 Years
STANDARD_DEVIATION 11.31 • n=8 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
38 Participants
n=21 Participants
|
163 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
2 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
3 participants
n=21 Participants
|
10 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Central/South Asian Heritage
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
2 participants
n=21 Participants
|
8 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Japanese/East Asian /South East Asian Heritage
|
9 participants
n=5 Participants
|
6 participants
n=7 Participants
|
11 participants
n=5 Participants
|
5 participants
n=4 Participants
|
14 participants
n=21 Participants
|
45 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
24 participants
n=5 Participants
|
27 participants
n=7 Participants
|
21 participants
n=5 Participants
|
6 participants
n=4 Participants
|
19 participants
n=21 Participants
|
97 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native and Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
1 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline until disease progression/recurrence was documented, assessed for up to 66 weeksPopulation: Modified Intent-to-Treat (mITT) Population: all randomized participants who received at least one dose of study treatment. The mITT1 Population was used for cohort 1; the mITT2 Population used for cohort 2.
RECIST-based response assessment was done at Weeks (Wks) 4 and 8 and every 8 weeks thereafter. Cutaneous disease assessment was done at Wk 4 and every 4 weeks thereafter. OR was evaluated when the skin and RECIST assessments coincided. Per RECIST, CR is the disappearance of all target and non-target lesions; PR is at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. Cutaneous disease contained non-measurable and measurable skin disease, which was assessed by skin assessment tools.
Outcome measures
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
n=38 Participants
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
n=38 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
n=36 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
n=13 Participants
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
n=38 Participants
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
|---|---|---|---|---|---|
|
Number of Participants With Overall Response (OR), Defined as Those Participants Achieving Complete Response (CR) or Partial Response (PR), Assessed Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 and Cutaneous Lesions
|
11 participants
|
17 participants
|
17 participants
|
4 participants
|
22 participants
|
SECONDARY outcome
Timeframe: From the date of the first documented evidence of CR or PR until the date of the first documented disease progression or death, assessed for up to 62 weeksPopulation: mITT1 and mITT2 Populations. Only participants who achieved a response of CR or PR during the study were analyzed. For participants who did not progress or die, duration of response was censored on the date of the last adequate assessment.
RECIST-based response assessment was done at Wks 4 and 8 and every 8 weeks thereafter. Cutaneous disease assessment was done at Wk 4 and every 4 weeks thereafter. OR was evaluated when the skin and RECIST assessments coincided. Per RECIST, PD is \>=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment started or the appearance of \>=1 new lesion and/or unequivocal progression of existing non-target lesions. Cutaneous disease contained non-measurable and measurable skin disease, which was assessed by skin assessment tools.
Outcome measures
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
n=11 Participants
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
n=17 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
n=17 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
n=4 Participants
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
n=22 Participants
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
|---|---|---|---|---|---|
|
Median Duration of Response,Defined as the First Documented Evidence of CR or PR Until the First Documentation of Disease Progression
|
16.9 weeks
Interval 12.4 to 21.0
|
13.0 weeks
Interval 9.1 to 28.1
|
13.6 weeks
Interval 10.0 to 19.9
|
31.2 weeks
Interval 3.4 to 33.1
|
12.7 weeks
Interval 8.0 to 16.1
|
SECONDARY outcome
Timeframe: From the date of the randomization until the earliest date of disease progression or death due to any cause, assessed for up to 66 weeksPopulation: mITT1 and mITT2 Populations
RECIST-based response assessment was done at Wks 4 and 8 and every 8 weeks thereafter. Cutaneous disease assessment was done at Wk 4 and every 4 weeks thereafter. OR was evaluated when the skin and RECIST assessments coincided. Per RECIST, PD is \>=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment started or the appearance of \>=1 new lesion and/or unequivocal progression of existing non-target lesions. Cutaneous disease contained non-measurable and measurable skin disease, which was assessed by skin assessment tools.
Outcome measures
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
n=38 Participants
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
n=38 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
n=36 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
n=13 Participants
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
n=38 Participants
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
|---|---|---|---|---|---|
|
Progression-free Survival, Defined as the Interval Between the Date of Randomization and the Earliest Date of Disease Progression (PD) or Death Due to Any Cause (Defined by an Investigator Review of Lesions Based on RECIST and Cutaneous Disease)
|
16.1 weeks
Interval 12.0 to 21.1
|
14.3 weeks
Interval 8.6 to 20.1
|
16.0 weeks
Interval 12.4 to 16.3
|
11.4 weeks
Interval 6.6 to 33.6
|
16.0 weeks
Interval 12.4 to 17.9
|
SECONDARY outcome
Timeframe: From the date of randomization until the date of death due to any cause, assessed for up to 163 weeksPopulation: mITT1 and mITT2 Populations
Overall survival is defined as the time from randomization until death due to any cause. For participants who did not die, time to death was censored at the time of last contact.
Outcome measures
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
n=38 Participants
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
n=38 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
n=36 Participants
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
n=13 Participants
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
n=38 Participants
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
|---|---|---|---|---|---|
|
Overall Survival
|
14.7 months
Interval 12.1 to 16.5
|
16.2 months
Interval 12.7 to 21.1
|
15.9 months
Interval 13.4 to
Due to an insufficient number of events, the upper limit of the confidence interval could not be calculated.
|
NA months
Interval 9.8 to
Due to an insufficient number of events, the median and the upper limit of the confidence interval could not be calculated.
|
NA months
Interval 12.4 to
Due to an insufficient number of events, the median and the upper limit of the confidence interval could not be calculated.
|
Adverse Events
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
Serious events: 6 serious events
Other events: 31 other events
Deaths: 0 deaths
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
Serious events: 14 serious events
Other events: 37 other events
Deaths: 0 deaths
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
Serious events: 4 serious events
Other events: 34 other events
Deaths: 0 deaths
Cohort 2: Pazopanib 800 mg
Serious events: 4 serious events
Other events: 13 other events
Deaths: 0 deaths
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
Serious events: 9 serious events
Other events: 35 other events
Deaths: 0 deaths
Open-label Lapatinib 1500 mg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
n=38 participants at risk
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
n=38 participants at risk
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
n=36 participants at risk
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
n=13 participants at risk
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
n=38 participants at risk
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Open-label Lapatinib 1500 mg
n=9 participants at risk
Participants who received pazopanib 800 mg in the randomized treatment phase were given the option to receive oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) QD.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
2.6%
1/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Nausea
|
2.6%
1/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/38
|
2.6%
1/38
|
2.8%
1/36
|
0.00%
0/13
|
7.9%
3/38
|
0.00%
0/9
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Investigations
Liver function test abnormal
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Infections and infestations
Empyema
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Infections and infestations
Sepsis
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Infections and infestations
Upper respiratory tract infection
|
2.6%
1/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Infections and infestations
Pneumonia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
2.6%
1/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnea
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.6%
1/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
General disorders
Sudden death
|
2.6%
1/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
General disorders
Fatigue
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
7.7%
1/13
|
2.6%
1/38
|
0.00%
0/9
|
|
General disorders
Asthenia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Hepatobiliary disorders
Cholestatic liver injury
|
2.6%
1/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Nervous system disorders
Headache
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Vascular disorders
Hypertension
|
0.00%
0/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Nervous system disorders
Subarachnoid hemorrhage
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Skin hemorrhage
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Eye injury
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to peritoneum
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
Other adverse events
| Measure |
Cohort 1: Lapatinib 1500 mg + Pazopanib Placebo
n=38 participants at risk
Participants received oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) once daily (QD).
|
Cohort 1: Lapatinib 1500 mg + Pazopanib 800 mg
n=38 participants at risk
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with pazopanib 800 mg (2 x 400 mg tablets) QD.
|
Cohort 2: Lapatinib 1500 mg + Pazopanib Placebo
n=36 participants at risk
Participants received oral lapatinib 1500 mg (6 x 250 mg tablets) in combination with placebo (matching to pazopanib; 2 tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Cohort 2: Pazopanib 800 mg
n=13 participants at risk
Participants received oral pazopanib 800 mg (4 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death. Participants who received pazopanib monotherapy and experienced unequivocal disease progression were given the option to receive lapatinib monotherapy in an open-label extension phase.
|
Cohort 2: Lapatinib 1000 mg + Pazopanib 400 mg
n=38 participants at risk
Participants received oral lapatinib 1000 mg (4 x 250 mg tablets) and 2 x 250 mg placebo tablets in combination with pazopanib 400 mg (2 x 200 mg tablets) QD. The study treatment continued until participants experienced disease progression, unacceptable toxicity, or death.
|
Open-label Lapatinib 1500 mg
n=9 participants at risk
Participants who received pazopanib 800 mg in the randomized treatment phase were given the option to receive oral lapatinib 1500 milligrams (mg) (6 x 250 mg tablets) QD.
|
|---|---|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Scab
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.9%
3/38
|
13.2%
5/38
|
2.8%
1/36
|
0.00%
0/13
|
7.9%
3/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.3%
2/38
|
7.9%
3/38
|
2.8%
1/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/38
|
7.9%
3/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.3%
2/38
|
2.6%
1/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Nervous system disorders
Headache
|
10.5%
4/38
|
18.4%
7/38
|
11.1%
4/36
|
0.00%
0/13
|
7.9%
3/38
|
11.1%
1/9
|
|
Nervous system disorders
Dizziness
|
0.00%
0/38
|
5.3%
2/38
|
2.8%
1/36
|
7.7%
1/13
|
15.8%
6/38
|
0.00%
0/9
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Nervous system disorders
Paraesthesia
|
5.3%
2/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
15.4%
2/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
5.3%
2/38
|
18.4%
7/38
|
0.00%
0/36
|
7.7%
1/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Infections and infestations
Urinary tract infection
|
7.9%
3/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/38
|
0.00%
0/38
|
5.6%
2/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Infections and infestations
Staphylococcal skin infection
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/38
|
13.2%
5/38
|
0.00%
0/36
|
30.8%
4/13
|
18.4%
7/38
|
0.00%
0/9
|
|
Blood and lymphatic system disorders
Anemia
|
5.3%
2/38
|
5.3%
2/38
|
11.1%
4/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/38
|
5.3%
2/38
|
5.6%
2/36
|
7.7%
1/13
|
21.1%
8/38
|
11.1%
1/9
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/38
|
5.3%
2/38
|
5.6%
2/36
|
15.4%
2/13
|
10.5%
4/38
|
11.1%
1/9
|
|
Endocrine disorders
Hypothyroidism
|
2.6%
1/38
|
5.3%
2/38
|
0.00%
0/36
|
15.4%
2/13
|
10.5%
4/38
|
0.00%
0/9
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
5.3%
2/38
|
5.3%
2/38
|
5.6%
2/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.5%
4/38
|
23.7%
9/38
|
8.3%
3/36
|
15.4%
2/13
|
18.4%
7/38
|
11.1%
1/9
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Metabolism and nutrition disorders
Enzyme abnormality
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Eye disorders
Dry eye
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/38
|
0.00%
0/38
|
5.6%
2/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/38
|
0.00%
0/38
|
5.6%
2/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Investigations
Platelet count increased
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Injury, poisoning and procedural complications
Chemical eye injury
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Gastrointestinal disorders
Diarrhea
|
39.5%
15/38
|
86.8%
33/38
|
55.6%
20/36
|
46.2%
6/13
|
57.9%
22/38
|
22.2%
2/9
|
|
Gastrointestinal disorders
Nausea
|
13.2%
5/38
|
44.7%
17/38
|
16.7%
6/36
|
15.4%
2/13
|
23.7%
9/38
|
22.2%
2/9
|
|
Gastrointestinal disorders
Vomiting
|
15.8%
6/38
|
39.5%
15/38
|
5.6%
2/36
|
30.8%
4/13
|
13.2%
5/38
|
11.1%
1/9
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.3%
2/38
|
10.5%
4/38
|
5.6%
2/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Stomatitis
|
5.3%
2/38
|
10.5%
4/38
|
0.00%
0/36
|
7.7%
1/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/38
|
7.9%
3/38
|
5.6%
2/36
|
15.4%
2/13
|
18.4%
7/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Constipation
|
5.3%
2/38
|
0.00%
0/38
|
8.3%
3/36
|
7.7%
1/13
|
2.6%
1/38
|
11.1%
1/9
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/38
|
0.00%
0/38
|
5.6%
2/36
|
7.7%
1/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Investigations
Alanine aminotransferase increased
|
10.5%
4/38
|
34.2%
13/38
|
22.2%
8/36
|
15.4%
2/13
|
21.1%
8/38
|
11.1%
1/9
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
General disorders
Fatigue
|
10.5%
4/38
|
36.8%
14/38
|
16.7%
6/36
|
23.1%
3/13
|
21.1%
8/38
|
0.00%
0/9
|
|
General disorders
Asthenia
|
10.5%
4/38
|
21.1%
8/38
|
2.8%
1/36
|
0.00%
0/13
|
10.5%
4/38
|
11.1%
1/9
|
|
General disorders
Mucosal inflammation
|
0.00%
0/38
|
15.8%
6/38
|
2.8%
1/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
General disorders
Pyrexia
|
5.3%
2/38
|
7.9%
3/38
|
2.8%
1/36
|
0.00%
0/13
|
7.9%
3/38
|
0.00%
0/9
|
|
General disorders
Hyperthermia
|
5.3%
2/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
General disorders
Malaise
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
General disorders
Edema peripheral
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Investigations
Aspartate aminotransferase increased
|
13.2%
5/38
|
34.2%
13/38
|
22.2%
8/36
|
23.1%
3/13
|
26.3%
10/38
|
11.1%
1/9
|
|
Investigations
Weight decreased
|
2.6%
1/38
|
13.2%
5/38
|
5.6%
2/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/38
|
13.2%
5/38
|
13.9%
5/36
|
7.7%
1/13
|
15.8%
6/38
|
0.00%
0/9
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/38
|
13.2%
5/38
|
0.00%
0/36
|
15.4%
2/13
|
10.5%
4/38
|
0.00%
0/9
|
|
Investigations
Blood alkaline phosphatase increased
|
5.3%
2/38
|
7.9%
3/38
|
8.3%
3/36
|
15.4%
2/13
|
10.5%
4/38
|
0.00%
0/9
|
|
Investigations
Blood pressure increased
|
2.6%
1/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
15.4%
2/13
|
7.9%
3/38
|
0.00%
0/9
|
|
Investigations
Platelet count decreased
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
15.4%
2/13
|
7.9%
3/38
|
0.00%
0/9
|
|
Investigations
Bilirubin conjugated increased
|
0.00%
0/38
|
0.00%
0/38
|
5.6%
2/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Investigations
Blood bicarbonate decreased
|
0.00%
0/38
|
0.00%
0/38
|
8.3%
3/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
7.7%
1/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Investigations
Blood sodium decreased
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
7.7%
1/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/38
|
0.00%
0/38
|
2.8%
1/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Investigations
Hemoglobin decreased
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
7.9%
3/38
|
0.00%
0/9
|
|
Investigations
Electrocardiogram ST segment depression
|
0.00%
0/38
|
0.00%
0/38
|
5.6%
2/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.2%
5/38
|
23.7%
9/38
|
30.6%
11/36
|
0.00%
0/13
|
31.6%
12/38
|
11.1%
1/9
|
|
Skin and subcutaneous tissue disorders
Acne
|
2.6%
1/38
|
13.2%
5/38
|
8.3%
3/36
|
0.00%
0/13
|
2.6%
1/38
|
11.1%
1/9
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.5%
4/38
|
7.9%
3/38
|
0.00%
0/36
|
0.00%
0/13
|
7.9%
3/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.9%
3/38
|
7.9%
3/38
|
2.8%
1/36
|
7.7%
1/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
7.9%
3/38
|
7.9%
3/38
|
5.6%
2/36
|
15.4%
2/13
|
5.3%
2/38
|
11.1%
1/9
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
5.3%
2/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.3%
2/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Hair color changes
|
0.00%
0/38
|
5.3%
2/38
|
2.8%
1/36
|
7.7%
1/13
|
15.8%
6/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
10.5%
4/38
|
2.6%
1/38
|
11.1%
4/36
|
7.7%
1/13
|
7.9%
3/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
5.3%
2/38
|
0.00%
0/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/38
|
0.00%
0/38
|
5.6%
2/36
|
0.00%
0/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
15.4%
2/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
11.1%
1/9
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.6%
1/38
|
15.8%
6/38
|
2.8%
1/36
|
7.7%
1/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.6%
1/38
|
7.9%
3/38
|
0.00%
0/36
|
7.7%
1/13
|
2.6%
1/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.3%
2/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.6%
1/38
|
5.3%
2/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.5%
4/38
|
2.6%
1/38
|
0.00%
0/36
|
7.7%
1/13
|
5.3%
2/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Clubbing
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/38
|
0.00%
0/38
|
0.00%
0/36
|
7.7%
1/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Vascular disorders
Hypertension
|
2.6%
1/38
|
28.9%
11/38
|
2.8%
1/36
|
23.1%
3/13
|
23.7%
9/38
|
0.00%
0/9
|
|
Vascular disorders
Hot flush
|
5.3%
2/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
|
Vascular disorders
Hematoma
|
0.00%
0/38
|
5.3%
2/38
|
0.00%
0/36
|
0.00%
0/13
|
0.00%
0/38
|
0.00%
0/9
|
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