Trial Outcomes & Findings for Association Between Genetic Polymorphism of Beta-adrenergic Receptor and Effects of Bisoprolol in Korean Heart Failure Patients. (NCT NCT01104558)

NCT ID: NCT01104558

Last Updated: 2014-02-13

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

100 participants

Primary outcome timeframe

Baseline and Week 26 (or EOT)

Results posted on

2014-02-13

Participant Flow

A total of 117 participants were screened for the study, out of which 17 were screen failures and 100 participants received the study medication.

Participant milestones

Participant milestones
Measure	Bisoprolol Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Overall Study STARTED	100
Overall Study COMPLETED	83
Overall Study NOT COMPLETED	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Bisoprolol Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Overall Study Protocol Violation	6
Overall Study Missing of primary efficacy assessment	10
Overall Study Missing of genetic analysis results	1

Baseline Characteristics

Association Between Genetic Polymorphism of Beta-adrenergic Receptor and Effects of Bisoprolol in Korean Heart Failure Patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bisoprolol n=100 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Age, Continuous	56.05 years STANDARD_DEVIATION 13.43 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Population: Efficacy intention to treat (ITT) population: all enrolled participants; treated with study drug; did not violate inclusion/exclusion criteria; and received primary efficacy assessment at least once after administration. "n" signifies number of participants with particular genotype and were evaluated for this outcome at particular time point.

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or End of Treatment (EOT) Baseline: Arg389Arg (n= 53)	32.44 Percent LVEF Standard Deviation 7.84
Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or End of Treatment (EOT) Baseline: Arg389Gly (n= 25)	32.89 Percent LVEF Standard Deviation 7.70
Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or End of Treatment (EOT) Baseline: Gly389Gly (n= 5)	32.20 Percent LVEF Standard Deviation 6.83
Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or End of Treatment (EOT) Change at Week 26 or EOT: Arg389Arg (n= 53)	-8.44 Percent LVEF Standard Deviation 9.00
Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or End of Treatment (EOT) Change at Week 26 or EOT: Arg389Gly (n= 25)	-9.36 Percent LVEF Standard Deviation 7.62
Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or End of Treatment (EOT) Change at Week 26 or EOT: Gly389Gly (n= 5)	-9.20 Percent LVEF Standard Deviation 5.63

PRIMARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Population: Efficacy ITT population: all enrolled participants; treated with study drug; did not violate inclusion/exclusion criteria; and received primary efficacy assessment at least once after administration. "n" signifies number of participants with particular genotype and were evaluated for this outcome at particular time point.

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	31.31 Percent LVEF Standard Deviation 8.97
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	32.67 Percent LVEF Standard Deviation 7.55
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 28)	33.03 Percent LVEF Standard Deviation 7.35
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	-9.39 Percent LVEF Standard Deviation 8.49
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	-7.87 Percent LVEF Standard Deviation 8.94
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 28)	-9.76 Percent LVEF Standard Deviation 7.57

PRIMARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	38.00 Percent LVEF Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	33.01 Percent LVEF Standard Deviation 7.30
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 67)	32.38 Percent LVEF Standard Deviation 7.82
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	-13.00 Percent LVEF Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	-8.71 Percent LVEF Standard Deviation 5.73
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 67)	-8.71 Percent LVEF Standard Deviation 8.94

PRIMARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of G Protein-coupled Receptor Kinase 5 (GRK5)-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	33.14 Percent LVEF Standard Deviation 7.46
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of G Protein-coupled Receptor Kinase 5 (GRK5)-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	29.87 Percent LVEF Standard Deviation 9.33
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of G Protein-coupled Receptor Kinase 5 (GRK5)-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 50)	-7.69 Percent LVEF Standard Deviation 7.73
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of G Protein-coupled Receptor Kinase 5 (GRK5)-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	-10.19 Percent LVEF Standard Deviation 8.93
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of G Protein-coupled Receptor Kinase 5 (GRK5)-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	-12.47 Percent LVEF Standard Deviation 13.27
Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of G Protein-coupled Receptor Kinase 5 (GRK5)-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 50)	32.37 Percent LVEF Standard Deviation 7.81

SECONDARY outcome

Timeframe: Baseline to Week 26 (or EOT)

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Number of Participants With Hospitalization Due to Heart Failure	1 Participants

SECONDARY outcome

Timeframe: Baseline to Week 26 (or EOT)

Population: Participant analyzed included 1 participant from the efficacy ITT population who was hospitalized once due to heart failure.

Outcome measures

Outcome measures
Measure	Bisoprolol n=1 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Duration of Hospitalization Due to Heart Failure	41 Days

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Population: Efficacy ITT population. N (number of participants analyzed) signifies those participants who were evaluated for this measure. "n" signifies number of participants with particular genotype and were evaluated for this outcome at particular time point.

6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	371.70 Meter Standard Deviation 128.16
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 53)	-20.85 Meter Standard Deviation 89.52
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	-0.90 Meter Standard Deviation 93.04
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	-20.10 Meter Standard Deviation 27.35
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 53)	401.36 Meter Standard Deviation 161.88
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 24)	381.71 Meter Standard Deviation 172.47

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 27)	-27.20 Meter Standard Deviation 117.54
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	449.43 Meter Standard Deviation 109.90
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	414.73 Meter Standard Deviation 155.27
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 27)	333.19 Meter Standard Deviation 179.71
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	0.46 Meter Standard Deviation 56.91
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	-12.18 Meter Standard Deviation 73.57

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	468.00 Meter Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	12.23 Meter Standard Deviation 106.68
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 66)	-20.51 Meter Standard Deviation 83.33
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	404.63 Meter Standard Deviation 175.65
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 66)	390.22 Meter Standard Deviation 160.83
Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	-57.00 Meter Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 49)	390.68 Meter Standard Deviation 160.61
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	395.11 Meter Standard Deviation 173.68
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 49)	-13.86 Meter Standard Deviation 79.64
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	-17.61 Meter Standard Deviation 104.93
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	-6.67 Meter Standard Deviation 25.66
Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	431.67 Meter Standard Deviation 42.52

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 53)	76.47 Beats per minute (bpm) Standard Deviation 12.90
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 24)	82.25 Beats per minute (bpm) Standard Deviation 14.66
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	83.20 Beats per minute (bpm) Standard Deviation 19.52
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 53)	8.91 Beats per minute (bpm) Standard Deviation 14.80
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	11.79 Beats per minute (bpm) Standard Deviation 15.13
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	12.00 Beats per minute (bpm) Standard Deviation 22.55

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	79.21 bpm Standard Deviation 13.96
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	79.02 bpm Standard Deviation 15.06
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 27)	77.56 bpm Standard Deviation 12.61
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	13.21 bpm Standard Deviation 12.71
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	9.20 bpm Standard Deviation 13.88
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 27)	9.37 bpm Standard Deviation 18.45

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	92.00 bpm Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	76.60 bpm Standard Deviation 11.47
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 66)	78.82 bpm Standard Deviation 14.52
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	9.00 bpm Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	10.33 bpm Standard Deviation 15.77
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 66)	9.86 bpm Standard Deviation 15.37

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 49)	77.29 bpm Standard Deviation 12.29
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	80.80 bpm Standard Deviation 16.54
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	77.33 bpm Standard Deviation 13.32
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 49)	10.92 bpm Standard Deviation 13.00
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	7.83 bpm Standard Deviation 18.69
Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	15.00 bpm Standard Deviation 13.00

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 53)	92.02 bpm Standard Deviation 19.82
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 24)	90.92 bpm Standard Deviation 21.37
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	92.80 bpm Standard Deviation 25.99
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 53)	11.83 bpm Standard Deviation 17.83
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	15.88 bpm Standard Deviation 16.54
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	4.60 bpm Standard Deviation 15.79

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	87.86 bpm Standard Deviation 18.53
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	95.05 bpm Standard Deviation 21.41
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 27)	88.74 bpm Standard Deviation 19.55
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	11.21 bpm Standard Deviation 15.34
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	12.37 bpm Standard Deviation 18.83
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 27)	13.59 bpm Standard Deviation 16.57

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	90.00 bpm Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	84.40 bpm Standard Deviation 15.89
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 66)	93.44 bpm Standard Deviation 21.16
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	-3.00 bpm Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	9.73 bpm Standard Deviation 13.10
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 66)	13.45 bpm Standard Deviation 18.24

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=82 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 49)	92.41 bpm Standard Deviation 20.87
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	89.30 bpm Standard Deviation 19.18
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	105.33 bpm Standard Deviation 25.70
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 49)	14.59 bpm Standard Deviation 16.16
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	8.53 bpm Standard Deviation 19.39
Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	20.00 bpm Standard Deviation 8.54

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Systolic Blood Pressure (SBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 52)	121.81 millimeters of mercury (mmHg) Standard Deviation 19.07
Change From Baseline in Systolic Blood Pressure (SBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 24)	123.54 millimeters of mercury (mmHg) Standard Deviation 15.91
Change From Baseline in Systolic Blood Pressure (SBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	117.40 millimeters of mercury (mmHg) Standard Deviation 15.09
Change From Baseline in Systolic Blood Pressure (SBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 52)	-0.96 millimeters of mercury (mmHg) Standard Deviation 15.09
Change From Baseline in Systolic Blood Pressure (SBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	-2.75 millimeters of mercury (mmHg) Standard Deviation 16.54
Change From Baseline in Systolic Blood Pressure (SBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	-0.40 millimeters of mercury (mmHg) Standard Deviation 25.07

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	132.36 mmHg Standard Deviation 27.18
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	117.83 mmHg Standard Deviation 14.61
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 26)	123.15 mmHg Standard Deviation 14.22
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	2.50 mmHg Standard Deviation 15.62
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	-4.32 mmHg Standard Deviation 15.69
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 26)	0.92 mmHg Standard Deviation 16.43

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	130.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	115.53 mmHg Standard Deviation 11.55
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 65)	123.43 mmHg Standard Deviation 18.85
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	-13.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	-4.33 mmHg Standard Deviation 12.31
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 65)	-0.62 mmHg Standard Deviation 16.79

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 48)	118.92 mmHg Standard Deviation 13.79
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	126.53 mmHg Standard Deviation 22.61
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	127.33 mmHg Standard Deviation 16.17
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 48)	-2.25 mmHg Standard Deviation 15.86
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	-1.13 mmHg Standard Deviation 16.78
Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	8.00 mmHg Standard Deviation 9.64

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 52)	128.77 mmHg Standard Deviation 20.95
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 24)	130.25 mmHg Standard Deviation 22.55
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	128.60 mmHg Standard Deviation 14.52
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 52)	-2.92 mmHg Standard Deviation 18.24
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	-0.46 mmHg Standard Deviation 22.31
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	5.40 mmHg Standard Deviation 23.64

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	138.71 mmHg Standard Deviation 25.63
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	126.56 mmHg Standard Deviation 19.78
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 26)	128.23 mmHg Standard Deviation 19.19
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	3.29 mmHg Standard Deviation 17.79
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	-4.34 mmHg Standard Deviation 20.96
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 26)	-0.15 mmHg Standard Deviation 18.59

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	113.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	124.47 mmHg Standard Deviation 9.62
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 65)	130.54 mmHg Standard Deviation 22.69
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	-18.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	-4.93 mmHg Standard Deviation 12.61
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 65)	-0.68 mmHg Standard Deviation 21.03

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 48)	127.52 mmHg Standard Deviation 17.67
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	131.27 mmHg Standard Deviation 25.87
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	135.33 mmHg Standard Deviation 16.04
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 48)	-2.10 mmHg Standard Deviation 20.08
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	-2.37 mmHg Standard Deviation 19.51
Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	12.00 mmHg Standard Deviation 15.10

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Diastolic Blood Pressure (DBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 52)	75.69 mmHg Standard Deviation 14.70
Change From Baseline in Diastolic Blood Pressure (DBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 24)	78.17 mmHg Standard Deviation 12.33
Change From Baseline in Diastolic Blood Pressure (DBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	79.40 mmHg Standard Deviation 5.55
Change From Baseline in Diastolic Blood Pressure (DBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 52)	0.10 mmHg Standard Deviation 13.13
Change From Baseline in Diastolic Blood Pressure (DBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	0.29 mmHg Standard Deviation 15.16
Change From Baseline in Diastolic Blood Pressure (DBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	0.60 mmHg Standard Deviation 11.70

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	83.14 mmHg Standard Deviation 22.76
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	75.59 mmHg Standard Deviation 11.11
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 26)	74.85 mmHg Standard Deviation 9.79
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	4.07 mmHg Standard Deviation 18.89
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	-0.88 mmHg Standard Deviation 10.39
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 26)	-0.23 mmHg Standard Deviation 14.71

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	68.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	71.80 mmHg Standard Deviation 8.90
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 65)	77.91 mmHg Standard Deviation 14.33
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	-28.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	-1.93 mmHg Standard Deviation 11.22
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 65)	1.11 mmHg Standard Deviation 13.66

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 48)	74.90 mmHg Standard Deviation 10.79
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	78.87 mmHg Standard Deviation 17.43
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	82.67 mmHg Standard Deviation 7.02
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 48)	0.06 mmHg Standard Deviation 12.93
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	-0.13 mmHg Standard Deviation 15.17
Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	5.33 mmHg Standard Deviation 1.15

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 52)	80.15 mmHg Standard Deviation 13.62
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 24)	80.50 mmHg Standard Deviation 12.60
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	81.80 mmHg Standard Deviation 8.50
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 52)	-0.04 mmHg Standard Deviation 13.66
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	3.63 mmHg Standard Deviation 11.86
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	1.00 mmHg Standard Deviation 14.04

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 26)	78.35 mmHg Standard Deviation 10.44
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	86.14 mmHg Standard Deviation 18.92
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	79.66 mmHg Standard Deviation 11.67
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	4.21 mmHg Standard Deviation 18.73
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 41)	-0.54 mmHg Standard Deviation 10.51
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 26)	2.04 mmHg Standard Deviation 13.44

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	65.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	77.40 mmHg Standard Deviation 6.31
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 65)	81.28 mmHg Standard Deviation 13.94
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	-21.00 mmHg Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	0.87 mmHg Standard Deviation 10.78
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 65)	1.51 mmHg Standard Deviation 13.48

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

Outcome measures

Outcome measures
Measure	Bisoprolol n=81 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 48)	79.10 mmHg Standard Deviation 11.08
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	81.97 mmHg Standard Deviation 15.98
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	84.33 mmHg Standard Deviation 4.04
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 48)	0.79 mmHg Standard Deviation 13.46
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	1.27 mmHg Standard Deviation 13.31
Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	4.67 mmHg Standard Deviation 5.51

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

BNP is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function.

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Pro-B-type Natriuretic Peptide (BNP) Levels According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Arg (n= 53)	1484.02 picograms (pg)/ milliliter (mL) Standard Deviation 3258.55
Change From Baseline in Pro-B-type Natriuretic Peptide (BNP) Levels According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Arg389Gly (n= 25)	851.47 picograms (pg)/ milliliter (mL) Standard Deviation 830.19
Change From Baseline in Pro-B-type Natriuretic Peptide (BNP) Levels According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gly389Gly (n= 5)	1011.30 picograms (pg)/ milliliter (mL) Standard Deviation 558.49
Change From Baseline in Pro-B-type Natriuretic Peptide (BNP) Levels According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Arg (n= 53)	292.10 picograms (pg)/ milliliter (mL) Standard Deviation 2452.11
Change From Baseline in Pro-B-type Natriuretic Peptide (BNP) Levels According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Arg389Gly (n= 24)	310.63 picograms (pg)/ milliliter (mL) Standard Deviation 643.97
Change From Baseline in Pro-B-type Natriuretic Peptide (BNP) Levels According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gly389Gly (n= 5)	394.32 picograms (pg)/ milliliter (mL) Standard Deviation 407.89

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Arg (n= 14)	2809.30 pg/mL Standard Deviation 5763.28
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Arg16Gly (n= 41)	823.71 pg/mL Standard Deviation 809.39
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Baseline: Gly16Gly (n= 28)	1139.07 pg/mL Standard Deviation 1691.51
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Arg (n= 14)	1600.88 pg/mL Standard Deviation 4294.99
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Arg16Gly (n= 40)	-33.98 pg/mL Standard Deviation 909.74
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT Change at Week 26 or EOT: Gly16Gly (n= 28)	137.68 pg/mL Standard Deviation 901.46

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Gln (n= 15)	878.31 pg/mL Standard Deviation 919.99
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Gln27Gln (n= 67)	1368.67 pg/mL Standard Deviation 2915.35
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Glu (n= 1)	84.91 pg/mL Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Glu27Gln (n= 15)	131.60 pg/mL Standard Deviation 902.50
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Change at Week 26 or EOT: Gln27Gln (n= 66)	346.20 pg/mL Standard Deviation 2187.04
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT Baseline: Glu27Glu (n= 1)	120.80 pg/mL Standard Deviation NA The standard deviation was not available because there was only 1 participant with this particular genotype.

SECONDARY outcome

Timeframe: Baseline and Week 26 (or EOT)

Outcome measures

Outcome measures
Measure	Bisoprolol n=83 Participants Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304 (n= 50)	895.52 pg/mL Standard Deviation 1291.90
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-Arg304His (n= 30)	1854.63 pg/mL Standard Deviation 4030.43
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-His304 (n= 3)	861.39 pg/mL Standard Deviation 1450.04
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Baseline: GRK5-His304 (n= 3)	1527.09 pg/mL Standard Deviation 1836.19
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304 (n= 49)	-33.78 pg/mL Standard Deviation 850.25
Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT Change at Week 26 or EOT: GRK5-Arg304His (n= 30)	799.31 pg/mL Standard Deviation 3052.03

Adverse Events

Bisoprolol

Serious events: 7 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bisoprolol n=100 participants at risk Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
General disorders Death sudden	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
General disorders Edema limbs	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Investigations INR increased	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Investigations Liver function test abnormal	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Musculoskeletal and connective tissue disorders Back pain	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Cerebral infarction	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Surgical and medical procedures Hospitalisation	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.

Other adverse events

Other adverse events
Measure	Bisoprolol n=100 participants at risk Bisoprolol tablet administered at a starting dose of 1.25 milligram (mg) once daily (OD) for two weeks and if it was well tolerated, the dose was increased to 2.5 mg , 3.75 mg, 5 mg OD in intervals of two weeks, 5 mg OD as a maintenance therapy, for a total time period of 26 weeks. If it was well tolerated, the dose was increased to a maximum of 10 mg/day.
Cardiac disorders Bradycardia	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Cardiac disorders Chest discomfort	6.0% 6/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Cardiac disorders Chest pain	6.0% 6/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Eye disorders Diabetic retinopathy	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Eye disorders Keratitis	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Abdominal discomfort	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Constipation	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Diarrhea	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Dry mouth	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Dyspepsia	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Epigastric discomfort	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Gingival bleeding	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Haematochezia	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Nausea	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Vomiting	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
General disorders Fatigue	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
General disorders General body pain	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
General disorders Pitting edema	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
General disorders Weakness generalized	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Herpes zoster	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Investigations Liver function test abnormal	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Investigations Weight increased	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Metabolism and nutrition disorders Diabetes mellitus	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Metabolism and nutrition disorders Hypertriglyceridemia	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Musculoskeletal and connective tissue disorders Back discomfort	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Musculoskeletal and connective tissue disorders Shoulder pain	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Dizziness	10.0% 10/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Dysarthria	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Head discomfort	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Near syncope	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Orthostatic dizziness	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Sleepiness	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Slurred speech	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Syncope	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Tingling feet/hands	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Psychiatric disorders Insomnia	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Renal and urinary disorders Voiding difficulty	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Reproductive system and breast disorders Nipple pain	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Common cold	7.0% 7/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Cough	5.0% 5/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Dry cough	2.0% 2/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.0% 5/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Sputum	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	4.0% 4/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Skin and subcutaneous tissue disorders Pruritus	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Vascular disorders Hypotension	1.0% 1/100 • Up to Week 26 (or EOT) An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.

Additional Information

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Principal investigator is a sponsor employee
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Restriction type: OTHER