Trial Outcomes & Findings for Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy (NCT NCT00753688)

Last Updated: 2013-08-22

Results Overview

PFS was defined as the time interval between the date of randomization and the earliest date of either disease progression or death due to any cause. The diagnosis of progression was based on tumor measurements, according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria, by independent radiologic assessment. The Kaplan-Meier method was used for PFS estimates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

369 participants

Primary outcome timeframe

From the date of randomization until the date of the first documented radiological progression or date of death from any cause, whichever came first (assessed for an average of 10 months)

Results posted on

2013-08-22

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Overall Study STARTED	123	246
Overall Study Ongoing - in Follow-up	15	31
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	123	246

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Overall Study Death	102	203
Overall Study Missing	4	9
Overall Study Participant Withdrew Consent	2	2
Overall Study Ongoing - in Follow-up	15	31
Overall Study Adverse Event	0	1

Baseline Characteristics

Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=123 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=246 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Total n=369 Participants Total of all reporting groups
Age Continuous	51.7 Years STANDARD_DEVIATION 13.77 • n=5 Participants	54.0 Years STANDARD_DEVIATION 14.92 • n=7 Participants	53.2 Years STANDARD_DEVIATION 14.57 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	147 Participants n=7 Participants	216 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	99 Participants n=7 Participants	153 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	7 participants n=5 Participants	24 participants n=7 Participants	31 participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	16 participants n=5 Participants	31 participants n=7 Participants	47 participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	89 participants n=5 Participants	174 participants n=7 Participants	263 participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 participants n=5 Participants	9 participants n=7 Participants	11 participants n=5 Participants
Number of participants in the indicated soft tissue sarcoma (STS) subgroups at Baseline Leiomyosarcoma	49 participants n=5 Participants	109 participants n=7 Participants	158 participants n=5 Participants
Number of participants in the indicated soft tissue sarcoma (STS) subgroups at Baseline Synovial sarcoma	13 participants n=5 Participants	25 participants n=7 Participants	38 participants n=5 Participants
Number of participants in the indicated soft tissue sarcoma (STS) subgroups at Baseline Other STS histologies	61 participants n=5 Participants	112 participants n=7 Participants	173 participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization until the date of the first documented radiological progression or date of death from any cause, whichever came first (assessed for an average of 10 months)

Population: Intent-to-Treat (ITT) Population: all randomized participants analyzed in the treatment arm they were allocated by randomization.

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=246 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Progression-free Survival (PFS)	7.0 weeks Interval 4.4 to 8.1	20.0 weeks Interval 17.9 to 21.3

SECONDARY outcome

Timeframe: From the date of randomization until 215 deaths (assessed for an average of 12 months)

Population: ITT Population

OS was defined as the time from the date of randomization to the date of death due to any cause. The length of this interval was calculated as the date of death minus the date of randomization plus 1 day. Participants who were alive at the time of analysis were censored at the date of last follow-up. The interim OS analysis was conducted when 215 (77 percent \[%\]) of the 279 required death events had occurred in the study. The Kaplan-Meier method was used for OS estimates.

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=246 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Overall Survival (OS)	10.7 months Interval 9.0 to 13.1	12.6 months Interval 10.9 to 14.9

SECONDARY outcome

Timeframe: From the start of treatment until disease progression (assessed for an average of 10 months)

Population: ITT Population

Overall response is defined as the number of participants who had a complete response (CR) or a partial response (PR). According to RECIST, Version 1.0: CR, disappearance of all lesions; PR, a \>=30% decrease in the sum of the longest dimensions (LD) of the target lesions (TLs) taking as a reference the baseline sum LD; Progressive disease (PD), a \>=20% increase in the sum of the LD of TLs, or the appearance of \>=1 new lesion; Stable Disease (SD), neither PR nor PD, persistence of \>=1 non-TL. Participants with no follow-up radiological disease assessment were categorized as not evaluable (NE).

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=246 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator CR, Independent radiologist assessed	0 participants	0 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator PR, Independent radiologist assessed	0 participants	11 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator SD, Independent radiologist assessed	33 participants	134 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator PD, Independent radiologist assessed	76 participants	66 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator NE, Independent radiologist assessed	14 participants	35 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator CR, Investigator assessed	0 participants	0 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator PR, Investigator assessed	0 participants	23 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator SD, Investigator assessed	36 participants	138 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator PD, Investigator assessed	83 participants	70 participants
Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator NE, Investigator assessed	4 participants	15 participants

SECONDARY outcome

Timeframe: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)

Population: ITT Population. Only participants who achieved a confirmed CR or PR, as determined independently by the Independent Radiologist and the Investigator, were analyzed. Only results for the pazopanib arm are given because there was no response in the placebo arm.

Time to response was defined as the time from the date of randomization until the date of first documented evidence of CR or PR (whichever status was recorded first). The Kaplan-Meier method was used for time to response estimates.

Outcome measures

Outcome measures
Measure	Placebo Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=23 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Time to Response Assessed by an Independent Radiologist and the Investigator Independent radiologist assessed, n=0, 11	—	8.4 weeks Interval 4.7 to 19.1
Time to Response Assessed by an Independent Radiologist and the Investigator Investigator assessed, n=0, 23	—	8.1 weeks Interval 4.6 to 11.7

SECONDARY outcome

Timeframe: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months)

Duration of response was defined as the time from the date of the first documented evidence of CR or PR until the date of either the first documented sign of PD or death due to any cause. Participants who neither died nor progressed were censored at the date of the last adequate radiologic assessment. The Kaplan-Meier method was used for duration of response estimates.

Outcome measures

Outcome measures
Measure	Placebo Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=23 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Duration of Response Assessed by the Independent Radiologist and the Investigator Independent radiologist assessed, n=0, 11	—	38.9 weeks Interval 16.7 to 40.0
Duration of Response Assessed by the Independent Radiologist and the Investigator Investigator assessed, n=0, 23	—	32.1 weeks Interval 22.6 to 44.0

SECONDARY outcome

Timeframe: From the date of randomization until the date of the first documented progression or the date of death from any cause, whichever came first (assessed for an average of 10 months)

Population: ITT Population. The "n"s in the category titles represent the number of participants in each treatment arm with the indicated STS.

PFS was defined as the time interval between the date of randomization and the earliest date of either disease progression or death due to any cause. Participants were analyzed for PFS in histology subgroups of STS (as per the World Health Organization \[WHO\] classification, 2008): leiomyosarcoma (malignant cancer of smooth muscle), synovial sarcoma (cancer near the joints of the arm or leg), and other STS (without the tumor type of leiomyosarcoma or synovial sarcoma), based on independent review.The Kaplan-Meier method was used for PFS estimates.

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=246 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS) Leiomyosarcoma, n=49, 109	8.1 weeks Interval 7.6 to 9.3	20.1 weeks Interval 13.3 to 23.1
PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS) Synovial sarcoma, n=13, 25	4.1 weeks Interval 3.7 to 8.9	17.9 weeks Interval 8.9 to 27.1
PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS) Other STS, n=61, 112	4.3 weeks Interval 4.0 to 7.9	20.1 weeks Interval 13.0 to 27.1

SECONDARY outcome

Timeframe: Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104

Population: Safety Population: all participants who had started their allocated treatment (at least one dose of the study drug). Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Change from baseline in on-therapy SBP and DBP was calculated as the values at the indicated time points (Day 8 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104) minus the value at baseline.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104

Population: Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Change from baseline in on-therapy heart rate was calculated as the value at the indicated time points (Day 8 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104) minus the value at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=113 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=225 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Change From Baseline in Heart Rate Week 72, n=1, 8	14.0 beats per minute Standard Deviation 0	2.6 beats per minute Standard Deviation 12.60
Change From Baseline in Heart Rate Day 8, n=113, 225	1.6 beats per minute Standard Deviation 12.61	-4.4 beats per minute Standard Deviation 11.24
Change From Baseline in Heart Rate Week 4, n=98, 208	3.1 beats per minute Standard Deviation 13.06	-2.7 beats per minute Standard Deviation 13.51
Change From Baseline in Heart Rate Week 8, n=66, 171	2.1 beats per minute Standard Deviation 15.03	-1.6 beats per minute Standard Deviation 14.31
Change From Baseline in Heart Rate Week 12, n=29, 103	1.1 beats per minute Standard Deviation 17.32	-2.4 beats per minute Standard Deviation 11.67
Change From Baseline in Heart Rate Week 16, n=31, 127	6.0 beats per minute Standard Deviation 16.78	-3.7 beats per minute Standard Deviation 12.76
Change From Baseline in Heart Rate Week 20, n=12, 57	0.6 beats per minute Standard Deviation 22.95	-3.4 beats per minute Standard Deviation 11.71
Change From Baseline in Heart Rate Week 24, n=21, 94	4.5 beats per minute Standard Deviation 18.14	-5.0 beats per minute Standard Deviation 12.83
Change From Baseline in Heart Rate Week 28, n=7, 37	-1.1 beats per minute Standard Deviation 27.99	-3.8 beats per minute Standard Deviation 13.68
Change From Baseline in Heart Rate Week 32, n=12, 72	-1.7 beats per minute Standard Deviation 18.38	-2.7 beats per minute Standard Deviation 12.63
Change From Baseline in Heart Rate Week 36, n=5, 24	-11.8 beats per minute Standard Deviation 32.57	0.9 beats per minute Standard Deviation 13.37
Change From Baseline in Heart Rate Week 40, n=5, 58	-8.2 beats per minute Standard Deviation 30.19	-2.4 beats per minute Standard Deviation 12.84
Change From Baseline in Heart Rate Week 44, n=3, 15	7.0 beats per minute Standard Deviation 16.09	-0.9 beats per minute Standard Deviation 14.02
Change From Baseline in Heart Rate Week 48, n=3, 33	9.0 beats per minute Standard Deviation 18.00	1.9 beats per minute Standard Deviation 14.38
Change From Baseline in Heart Rate Week 52, n=1, 5	-8.0 beats per minute Standard Deviation 0	-3.4 beats per minute Standard Deviation 16.96
Change From Baseline in Heart Rate Week 56, n=1, 24	31.0 beats per minute Standard Deviation 0	-0.4 beats per minute Standard Deviation 15.14
Change From Baseline in Heart Rate Week 60, n=0, 6	0 beats per minute Standard Deviation 0	4.3 beats per minute Standard Deviation 15.13
Change From Baseline in Heart Rate Week 64, n=1, 13	36.0 beats per minute Standard Deviation 0	-1.5 beats per minute Standard Deviation 13.56
Change From Baseline in Heart Rate Week 68, n=0, 2	0 beats per minute Standard Deviation 0	9.5 beats per minute Standard Deviation 0.71
Change From Baseline in Heart Rate Week 76, n=0, 1	0 beats per minute Standard Deviation 0	5.0 beats per minute Standard Deviation 0
Change From Baseline in Heart Rate Week 80, n=1, 5	24.0 beats per minute Standard Deviation 0	2.8 beats per minute Standard Deviation 16.08
Change From Baseline in Heart Rate Week 88, n=1, 3	9.0 beats per minute Standard Deviation 0	-3.0 beats per minute Standard Deviation 10.58
Change From Baseline in Heart Rate Week 96, n=1, 2	17.0 beats per minute Standard Deviation 0	-5.0 beats per minute Standard Deviation 4.24
Change From Baseline in Heart Rate Week 104, n=1, 1	30.0 beats per minute Standard Deviation 0	1.0 beats per minute Standard Deviation 0

SECONDARY outcome

Timeframe: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)

Population: Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Shifts in hematology values by grade were summarized based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE Version 3.0). Grade refers to the severity of the AE. The CTCAE Version 3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline. Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 (severe AE) and 4 (life-threatening or disabling AE) at any point in the study after baseline are reported.

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=239 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Hemoglobin, Any Increase, n=123, 239	28 participants	65 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Hemoglobin, Increase to Grade 3, n=123, 239	1 participants	11 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Hemoglobin, Increase to Grade 4, n=123, 239	1 participants	4 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Lymphocytes, Any Increase, n=123, 238	44 participants	102 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Lymphocytes, Increase to Grade 3, n=123, 238	11 participants	23 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Lymphocytes, Increase to Grade 4, n=123, 238	2 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Neutrophils, Any Increase, n=123, 239	8 participants	79 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Neutrophils, Increase to Grade 3, n=123, 239	0 participants	10 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Neutrophils, Increase to Grade 4, n=123, 239	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Platelets, Any Increase, n=123, 239	7 participants	86 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Platelets, Increase to Grade 3, n=123, 239	0 participants	7 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count Platelets, Increase to Grade 4, n=123, 239	0 participants	2 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count White Blood Cells, Any Increase, n=123, 239	18 participants	106 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count White Blood Cells, Increase to Grade 3, n=123, 239	0 participants	3 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count White Blood Cells, Increase to Grade , n=123, 239	0 participants	0 participants

SECONDARY outcome

Timeframe: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)

Population: Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Shifts in clinical chemistry values by grade were summarized based on the NCI CTCAE Version 3.0. Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 and 4 at any point in the study after baseline are reported. alkaline phosphatase, ALKP; alanine aminotransferase, ALT; aspartate aminotransferase, AST. Hyper/hypoglycemia refers to high/low glucose; hyper/hypokalemia refers to high/low potassium; hyper/hyponatremia refers to high/low sodium.

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=239 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin ALKP, Any Increase, n=123, 237	28 participants	77 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin ALKP, Increase to Grade 3, n=123, 237	1 participants	7 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin ALKP, Increase to Grade 4, n=123, 237	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin ALT, Any Increase, n=123, 237	22 participants	110 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin ALT, Increase to Grade 3, n=123, 237	3 participants	18 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin ALT, Increase to Grade 4, n=123, 237	1 participants	5 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin AST, Any Increase, n=123, 239	27 participants	122 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin AST, Increase to Grade 3, n=123, 239	2 participants	13 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin AST, Increase to Grade 4, n=123, 239	0 participants	6 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Albumin, Any Increase, n=123, 239	26 participants	81 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Albumin, Increase to Grade 3, n=123, 239	0 participants	2 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Albumin, Increase to Grade 4, n=123, 239	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Creatinine, Any Increase, n=123, 239	9 participants	28 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Creatinine, Increase to Grade 3, n=123, 239	0 participants	1 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Creatinine, Increase to Grade 4, n=123, 239	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyperglycemia, Any Increase, n=122, 238	43 participants	106 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyperglycemia, Increase to Grade 3, n=122, 238	2 participants	1 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyperglycemia, Increase to Grade 4, n=122, 238	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyperkalemia, Any Increase, n=123, 238	13 participants	37 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyperkalemia, Increase to Grade 3, n=123, 238	0 participants	3 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyperkalemia, Increase to Grade 4, n=123, 238	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypernatremia, Any Increase, n=123, 238	3 participants	10 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypernatremia, Increase to Grade 3, n=123, 238	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypernatremia, Increase to Grade 4, n=123, 238	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypoglycemia, Any Increase, n=122, 238	4 participants	21 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypoglycemia, Increase to Grade 3, n=122, 238	0 participants	1 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypoglycemia, Increase to Grade 4, n=122, 238	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypokalemia, Any Increase, n=123, 238	11 participants	32 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypokalemia, Increase to Grade 3, n=123, 238	1 participants	6 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hypokalemia, Increase to Grade 4, n=123, 238	0 participants	1 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyponatremia, Any Increase, n=123, 238	25 participants	74 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyponatremia, Increase to Grade 3, n=123, 238	4 participants	9 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Hyponatremia, Increase to Grade 4, n=123, 238	0 participants	0 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Total Bilirubin, Any Increase, n=122, 237	9 participants	68 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Total Bilirubin, Increase to Grade 3, n=122, 237	2 participants	3 participants
Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin Total Bilirubin, Increase to Grade 4, n=122, 237	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (within 14 days of the first dose of study drug) and any time post-baseline until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)

Population: Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function (based on the institutional lower limit of normal \[LLN\]). LVEF was assessed at BL, Week 12, and every second scheduled visit thereafter until study drug discontinuation and end of treatment or as clinically indicated by using multi-gated acquisition scan (MUGA) or echocardiogram (ECHO). Absolute change from BL was calculated as the on-study value minus the baseline value (LVEF is calculated as a percentage).

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=140 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) Any Increase	15 participants	39 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) No Change	6 participants	14 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) 0 to <10% Decrease	15 participants	66 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) 10 to 19% Decrease	3 participants	15 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) >=20% Decrease	0 participants	6 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) >=10% Decrease and >= LLN	3 participants	8 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) >=10% Decrease and below LLN	0 participants	13 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) >=20% Decrease and >= LLN	0 participants	1 participants
Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy) >=20% Decrease and below LLN	0 participants	5 participants

Adverse Events

Placebo

Serious events: 29 serious events

Other events: 108 other events

Deaths: 0 deaths

Pazopanib

Serious events: 99 serious events

Other events: 232 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	Placebo n=120 Participants Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	Pazopanib n=235 Participants Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 8, n=120, 235	-0.6 Millimeters of mercury Standard Deviation 13.37	10.3 Millimeters of mercury Standard Deviation 15.96
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 4, n=106, 224	-0.2 Millimeters of mercury Standard Deviation 12.83	10.9 Millimeters of mercury Standard Deviation 19.47
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 8, n=71, 180	0.0 Millimeters of mercury Standard Deviation 13.60	7.2 Millimeters of mercury Standard Deviation 17.46
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 12, n=31, 115	-3.1 Millimeters of mercury Standard Deviation 15.82	4.9 Millimeters of mercury Standard Deviation 18.21
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 16, n=35, 136	-0.6 Millimeters of mercury Standard Deviation 15.91	4.9 Millimeters of mercury Standard Deviation 18.49
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 20, n=14, 66	-2.6 Millimeters of mercury Standard Deviation 14.89	3.9 Millimeters of mercury Standard Deviation 19.84
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 24, n=22, 107	-3.8 Millimeters of mercury Standard Deviation 16.71	2.7 Millimeters of mercury Standard Deviation 20.24
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 28, n=9, 41	0.2 Millimeters of mercury Standard Deviation 22.82	0.9 Millimeters of mercury Standard Deviation 15.70
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 32, n=12, 76	2.8 Millimeters of mercury Standard Deviation 12.50	3.2 Millimeters of mercury Standard Deviation 18.89
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 36, n=5, 24	3.6 Millimeters of mercury Standard Deviation 10.71	1.9 Millimeters of mercury Standard Deviation 17.71
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 40, n=5, 62	6.8 Millimeters of mercury Standard Deviation 15.47	3.2 Millimeters of mercury Standard Deviation 19.75
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 44, n=3, 16	6.0 Millimeters of mercury Standard Deviation 19.31	1.2 Millimeters of mercury Standard Deviation 19.45
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 48, n=3, 37	-1.7 Millimeters of mercury Standard Deviation 14.05	-1.7 Millimeters of mercury Standard Deviation 16.90
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 52, n=1, 6	-4.0 Millimeters of mercury Standard Deviation 0	9.8 Millimeters of mercury Standard Deviation 18.28
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 56, n=1, 27	16.0 Millimeters of mercury Standard Deviation 0	1.4 Millimeters of mercury Standard Deviation 20.86
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 60, n=0, 6	0 Millimeters of mercury Standard Deviation 0	7.0 Millimeters of mercury Standard Deviation 18.60
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 64, n=1, 15	20.0 Millimeters of mercury Standard Deviation 0	-3.0 Millimeters of mercury Standard Deviation 19.26
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 68, n=0, 2	0 Millimeters of mercury Standard Deviation 0	14.5 Millimeters of mercury Standard Deviation 3.54
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 72, n=1, 9	8.0 Millimeters of mercury Standard Deviation 0	-1.1 Millimeters of mercury Standard Deviation 15.83
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 76, n=0, 1	0 Millimeters of mercury Standard Deviation 0	16.0 Millimeters of mercury Standard Deviation 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 80, n=1, 5	19.0 Millimeters of mercury Standard Deviation 0	-0.9 Millimeters of mercury Standard Deviation 22.66
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 88, n=1, 3	3.0 Millimeters of mercury Standard Deviation 0	3.9 Millimeters of mercury Standard Deviation 22.90
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 96, n=1, 2	13.0 Millimeters of mercury Standard Deviation 0	-3.0 Millimeters of mercury Standard Deviation 14.14
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 104, n=1, 1	18.0 Millimeters of mercury Standard Deviation 0	6.0 Millimeters of mercury Standard Deviation 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 8, n=120, 235	-0.2 Millimeters of mercury Standard Deviation 9.53	7.2 Millimeters of mercury Standard Deviation 10.68
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 4, n=106, 224	-0.2 Millimeters of mercury Standard Deviation 9.51	8.2 Millimeters of mercury Standard Deviation 11.37
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 8, n=71, 180	-0.3 Millimeters of mercury Standard Deviation 9.24	6.6 Millimeters of mercury Standard Deviation 12.18
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 12, n=31, 115	-0.1 Millimeters of mercury Standard Deviation 10.81	3.9 Millimeters of mercury Standard Deviation 11.31
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 16, n=35, 136	0.8 Millimeters of mercury Standard Deviation 10.46	5.3 Millimeters of mercury Standard Deviation 12.12
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 20, n=14, 66	-0.3 Millimeters of mercury Standard Deviation 8.61	4.5 Millimeters of mercury Standard Deviation 12.22
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 24, n=22, 107	-1.6 Millimeters of mercury Standard Deviation 11.78	3.7 Millimeters of mercury Standard Deviation 14.44
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 28, n=9, 41	-1.9 Millimeters of mercury Standard Deviation 12.33	3.7 Millimeters of mercury Standard Deviation 11.28
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 32, n=12, 76	-2.0 Millimeters of mercury Standard Deviation 7.30	3.9 Millimeters of mercury Standard Deviation 11.59
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 36, n=5, 24	-6.6 Millimeters of mercury Standard Deviation 9.63	4.1 Millimeters of mercury Standard Deviation 13.28
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 40, n=5, 62	3.4 Millimeters of mercury Standard Deviation 9.24	2.9 Millimeters of mercury Standard Deviation 13.34
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 44, n=3, 16	4.7 Millimeters of mercury Standard Deviation 5.03	1.7 Millimeters of mercury Standard Deviation 12.48
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 48, n=3, 37	2.0 Millimeters of mercury Standard Deviation 4.36	3.7 Millimeters of mercury Standard Deviation 12.01
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 52, n=1, 6	1.0 Millimeters of mercury Standard Deviation 0	12.0 Millimeters of mercury Standard Deviation 15.06
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 56, n=1, 27	12.0 Millimeters of mercury Standard Deviation 0	4.4 Millimeters of mercury Standard Deviation 12.28
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 60, n=0, 6	0 Millimeters of mercury Standard Deviation 0	12.7 Millimeters of mercury Standard Deviation 14.39
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 64, n=1, 15	10.0 Millimeters of mercury Standard Deviation 0	-2.2 Millimeters of mercury Standard Deviation 14.21
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 68, n=0, 2	0 Millimeters of mercury Standard Deviation 0	17.0 Millimeters of mercury Standard Deviation 25.46
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 72, n=1, 9	13.0 Millimeters of mercury Standard Deviation 0	0.8 Millimeters of mercury Standard Deviation 12.88
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 76, n=0, 1	0 Millimeters of mercury Standard Deviation 0	4.0 Millimeters of mercury Standard Deviation 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 80, n=1, 5	14.0 Millimeters of mercury Standard Deviation 0	-3.3 Millimeters of mercury Standard Deviation 15.15
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 88, n=1, 3	9.0 Millimeters of mercury Standard Deviation 0	5.2 Millimeters of mercury Standard Deviation 3.87
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 96, n=1, 2	6.0 Millimeters of mercury Standard Deviation 0	7.0 Millimeters of mercury Standard Deviation 5.66
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 104, n=1, 1	12.0 Millimeters of mercury Standard Deviation 0	12.0 Millimeters of mercury Standard Deviation 0