Hypertension
Conditions
Keywords
Hypertension, Diabetes Mellitus, Bisoprolol
Brief summary
The aim of this 12-week, multicenter, interventional, prospective, open-label and single-arm study is to evaluate the safety and efficacy of 5 milligram per day (mg/day) and 10 mg/day bisoprolol in Filipino hypertensive subjects with diabetes as monotherapy or as an add-on therapy.
Interventions
DRUGBisoprolol
Bisoprolol will be administered at an initial dose of 5 milligram (mg) once daily for 2 weeks. If the blood pressure would be greater than or equal to 130/80 mmHg after 2 weeks, then dose will be adjusted to 10 mg once daily. Total duration of study treatment will be 12 weeks.
Sponsors
Merck Inc., Philippines
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult subjects with hypertension, either newly diagnosed or treated but currently uncontrolled as defined by Joint National Committee (JNC) 7 for subjects with Type 2 diabetes mellitus (T2DM) (that is, greater than or equal to \[\>=\] 130/80 mmHg) * Aged at least 18 years old * Diagnosed with T2DM and already on anti-diabetic therapy, and with glycosylated hemoglobin of less than 7 percent
Exclusion criteria
* Subjects who were already on beta-blocker therapy at the time of recruitment * Subjects with heart rate of at most 60 beats per minute (bpm) at rest * Subjects with secondary hypertension, congenital heart disease, coronary artery disease, peripheral arterial disease or congestive heart failure in any stage * Subjects with coronary conduction disorders (bundle branch block) * Subjects with signs of definitive target organ damage consistent with World Health Organization (WHO) Stage III or with severe renal or hepatic disease * Subjects who are pregnant or expect to be pregnant within the 24-week study period * Subjects on oral contraceptives * Subjects with asthma or a history of asthma * Subjects with documented severe renal disease * Subjects on anti-neoplastic drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 12 | Baseline, Week 12 | The change in diastolic and systolic BP at Week 12 was calculated as diastolic and systolic BP at Week 12 minus diastolic and systolic BP at baseline, respectively. |
| Percentage of Participants With Controlled BP | Week 12 | Controlled BP was defined as BP less than 130/80 mmHg. |
| Percentage of Participants With Response to Study Drug | Week 12 | Response to study drug was defined as lowering of systolic BP by at least 10 mmHg from baseline. |
| Mean Change From Baseline in Heart Rate at Week 12 | Baseline, Week 12 | The change in heart rate at Week 12 was calculated as the heart rate at Week 12 minus heart rate at baseline. |
| Percentage of Participants With Decrease in Heart Rate by at Least 10 Bpm at Week 12 | Week 12 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Increased Glycosylated Hemoglobin (HbA1c) at Week 12 | Week 12 | HbA1c represents the percentage of glycosylated hemoglobin. Percentage of participants with increased HbA1c (greater than 0.5% from baseline) at Week 12 was reported. |
| Number of Participants With Adverse Events (AEs) | Baseline up to Week 12 | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. |
| Mean Change From Baseline in HbA1c at Week 12 | Baseline, Week 12 | HbA1c represents the percentage of glycosylated hemoglobin. The change in HbA1c at Week 12 was calculated as HbA1c at Week 12 minus HbA1c at baseline. |
| Percentage of Participants With Increased Fasting Blood Sugar (FBS) at Week 12 | Week 12 | Percentage of participants with increased FBS (greater than 16 milligram per deciliter \[mg/dL\] from baseline) at Week 12 was reported. |
| Mean Change From Baseline in Fasting Blood Sugar (FBS) Level at Week 12 | Baseline, Week 12 | The change in FBS level at Week 12 was calculated as FBS level at Week 12 minus FBS level at baseline. |
| Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | Baseline, Week 12 | The change in total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride level at Week 12 was calculated as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride level at Week 12 minus total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride level at baseline, respectively. |
Countries
Philippines
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bisoprolol Bisoprolol was administered at an initial dose of 5 milligram (mg) once daily for 2 weeks. If the blood pressure was greater than or equal to 130/80 millimeter of mercury (mmHg) after 2 weeks, then the dose was adjusted to 10 mg once daily. Total duration of study treatment was 12 weeks. | 125 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 35 |
| Overall Study | Other | 4 |
Baseline characteristics
| Characteristic | Bisoprolol |
|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 12.1 |
| Gender Female | 73 Participants |
| Gender Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 125 |
| serious Total, serious adverse events | 0 / 125 |
Outcome results
Primary
Mean Change From Baseline in Heart Rate at Week 12
The change in heart rate at Week 12 was calculated as the heart rate at Week 12 minus heart rate at baseline.
Time frame: Baseline, Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Mean Change From Baseline in Heart Rate at Week 12 | Baseline | 78.2 beats per minute (bpm) | Standard Deviation 9.2 |
| Bisoprolol | Mean Change From Baseline in Heart Rate at Week 12 | Change at Week 12 | 8.55 beats per minute (bpm) | Standard Deviation 9.24 |
Primary
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 12
The change in diastolic and systolic BP at Week 12 was calculated as diastolic and systolic BP at Week 12 minus diastolic and systolic BP at baseline, respectively.
Time frame: Baseline, Week 12
Population: Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 12 | Systolic BP: Baseline | 151.7 mmHg | Standard Deviation 20.1 |
| Bisoprolol | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 12 | Systolic BP: Change at Week 12 | 12.54 mmHg | Standard Deviation 18.39 |
| Bisoprolol | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 12 | Diastolic BP: Baseline | 87.6 mmHg | Standard Deviation 8.2 |
| Bisoprolol | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 12 | Diastolic BP: Change at Week 12 | 8.48 mmHg | Standard Deviation 10.01 |
Primary
Percentage of Participants With Controlled BP
Controlled BP was defined as BP less than 130/80 mmHg.
Time frame: Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bisoprolol | Percentage of Participants With Controlled BP | 42.4 percentage of participants |
Primary
Percentage of Participants With Decrease in Heart Rate by at Least 10 Bpm at Week 12
Time frame: Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bisoprolol | Percentage of Participants With Decrease in Heart Rate by at Least 10 Bpm at Week 12 | 36.8 percentage of participants |
Primary
Percentage of Participants With Response to Study Drug
Response to study drug was defined as lowering of systolic BP by at least 10 mmHg from baseline.
Time frame: Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bisoprolol | Percentage of Participants With Response to Study Drug | 44.0 percentage of participants |
Secondary
Mean Change From Baseline in Fasting Blood Sugar (FBS) Level at Week 12
The change in FBS level at Week 12 was calculated as FBS level at Week 12 minus FBS level at baseline.
Time frame: Baseline, Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Mean Change From Baseline in Fasting Blood Sugar (FBS) Level at Week 12 | Baseline | 117.1 mg/dL | Standard Deviation 25.8 |
| Bisoprolol | Mean Change From Baseline in Fasting Blood Sugar (FBS) Level at Week 12 | Change at Week 12 | -5.49 mg/dL | Standard Deviation 25.83 |
Secondary
Mean Change From Baseline in HbA1c at Week 12
HbA1c represents the percentage of glycosylated hemoglobin. The change in HbA1c at Week 12 was calculated as HbA1c at Week 12 minus HbA1c at baseline.
Time frame: Baseline, Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Mean Change From Baseline in HbA1c at Week 12 | Baseline | 6.28 Percent HbA1c | Standard Deviation 0.43 |
| Bisoprolol | Mean Change From Baseline in HbA1c at Week 12 | Change at Week 12 | 0.02 Percent HbA1c | Standard Deviation 0.59 |
Secondary
Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12
The change in total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride level at Week 12 was calculated as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride level at Week 12 minus total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride level at baseline, respectively.
Time frame: Baseline, Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | Total cholesterol: Baseline | 183.7 mg/dL | Standard Deviation 39.7 |
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | Total cholesterol: Change at Week 12 | 1.25 mg/dL | Standard Deviation 32.14 |
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | LDL cholesterol: Baseline | 105.5 mg/dL | Standard Deviation 31 |
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | LDL cholesterol: Change at Week 12 | -1.20 mg/dL | Standard Deviation 22.4 |
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | HDL cholesterol: Baseline | 52.0 mg/dL | Standard Deviation 15.6 |
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | HDL cholesterol: Change at Week 12 | 0.88 mg/dL | Standard Deviation 12.23 |
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | Triglyceride: Baseline | 122.8 mg/dL | Standard Deviation 55.2 |
| Bisoprolol | Mean Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Week 12 | Triglyceride: Change at Week 12 | 2.59 mg/dL | Standard Deviation 38.32 |
Secondary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship.
Time frame: Baseline up to Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bisoprolol | Number of Participants With Adverse Events (AEs) | 8 participants |
Secondary
Percentage of Participants With Increased Fasting Blood Sugar (FBS) at Week 12
Percentage of participants with increased FBS (greater than 16 milligram per deciliter \[mg/dL\] from baseline) at Week 12 was reported.
Time frame: Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bisoprolol | Percentage of Participants With Increased Fasting Blood Sugar (FBS) at Week 12 | 15.2 percentage of participants |
Secondary
Percentage of Participants With Increased Glycosylated Hemoglobin (HbA1c) at Week 12
HbA1c represents the percentage of glycosylated hemoglobin. Percentage of participants with increased HbA1c (greater than 0.5% from baseline) at Week 12 was reported.
Time frame: Week 12
Population: ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Bisoprolol | Percentage of Participants With Increased Glycosylated Hemoglobin (HbA1c) at Week 12 | 16.8 percentage of participants | 0.6 |