Hypertension
Conditions
Keywords
safety and tolerability study, hypertension, beta-blockers
Brief summary
The purpose of this study is to evaluate long-term safety,tolerability and blood pressure effects of metoprolol versus nebivolol in patients with hypertension. These drugs may be given alone or in combination with other drugs that are commonly used in the treatment of hypertension
Detailed description
Approximately 50 million Americans have hypertension defined as a systolic blood pressure (SBP) greater then or equal to 140 mmHg and/or a diastolic blood pressure (DBP) greater then or equal to 90 mmHg. To control blood pressure, more than 2 agents are required in many patients. The current study is a randomized, titration-to-effect, open-label, multi center study. Patients will be randomized to either nebivolol or metoprolol. The dose of the randomized treatment can be titrated as needed to achieve blood pressure control. If necessary, additional antihypertensive agents (calcium antagonist, diuretic, etc.) can be added to achieve control. Patients will be seen every 1-3 months for approximately 18 months to assess long-term safety, tolerability and effectiveness of nebivolol versus metoprolol.
Interventions
DRUGNebivolol (NEB)
Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.
DRUGMetoprolol (MET)
Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Sponsors
Mylan Bertek Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of previous nebivolol study * Stage 1-2 Hypertension (HTN) at baseline of first study
Exclusion criteria
* Recent myocardial infarction or stroke * Contraindications to beta blocker therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline | Through study duration (approximately 18 months) | The primary efficacy parameter was the change in the average trough sitting DBP at the end of treatment (Visit 10 or Early Termination) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 \[NCT00145210\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Through study completion (approximately 18 months) | Data for the analysis of the change from baseline in mean trough sitting DBP at each study visit (Visits 1 through 9) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 \[NCT00145210\]) by treatment group are provided below. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Through study completion (approximately 18 months) | Summary of Participants that experienced one or more TEAEs by Treatment Group-Safety Population |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1-NEB Nebivolol
Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks. | 252 |
| 2-MET Metoprolol
Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks. | 84 |
| Total | 336 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 5 |
| Overall Study | Lost to Follow-up | 22 | 12 |
| Overall Study | Protocol Violation | 4 | 7 |
| Overall Study | Sponsor Termination of Study, etc. | 72 | 16 |
| Overall Study | Treatment Failure | 2 | 0 |
| Overall Study | Withdrawal by Subject | 30 | 16 |
Baseline characteristics
| Characteristic | 2-MET | Total | 1-NEB |
|---|---|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 9.76 | 50.6 years STANDARD_DEVIATION 9.83 | 50.8 years STANDARD_DEVIATION 9.86 |
| Race/Ethnicity, Customized Black | 84 Participants | 336 Participants | 252 Participants |
| Region of Enrollment United States | 84 participants | 336 participants | 252 participants |
| Sex: Female, Male Female | 44 Participants | 174 Participants | 130 Participants |
| Sex: Female, Male Male | 40 Participants | 162 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 252 | 0 / 84 |
| other Total, other adverse events | 74 / 252 | 28 / 84 |
| serious Total, serious adverse events | 11 / 252 | 2 / 84 |
Outcome results
Primary
Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline
The primary efficacy parameter was the change in the average trough sitting DBP at the end of treatment (Visit 10 or Early Termination) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 \[NCT00145210\]).
Time frame: Through study duration (approximately 18 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1-NEB | Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline | -14.0 mm Hg | Standard Deviation 9.8 |
| 2-MET | Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline | -10.9 mm Hg | Standard Deviation 8.73 |
Secondary
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline
Data for the analysis of the change from baseline in mean trough sitting DBP at each study visit (Visits 1 through 9) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 \[NCT00145210\]) by treatment group are provided below.
Time frame: Through study completion (approximately 18 months)
Population: The overall number of participants analyzed equals the number of randomized patients at study start; the numbers analyzed at each visit equal the number of patients at each treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 2 | -8.4 mm Hg | Standard Deviation 8.39 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 6 | -14.5 mm Hg | Standard Deviation 8.49 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 4 | -12.1 mm Hg | Standard Deviation 8.55 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 7 | -15.5 mm Hg | Standard Deviation 8.55 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 3 | -10.6 mm Hg | Standard Deviation 8.51 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 8 | -16.3 mm Hg | Standard Deviation 8.59 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 5 | -13.0 mm Hg | Standard Deviation 8.03 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 9 | -16.7 mm Hg | Standard Deviation 7.91 |
| 1-NEB | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 1 | -8.3 mm Hg | Standard Deviation 8.24 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 9 | -13.7 mm Hg | Standard Deviation 7.05 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 1 | -8.4 mm Hg | Standard Deviation 9.15 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 2 | -8.4 mm Hg | Standard Deviation 7.89 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 3 | -9.8 mm Hg | Standard Deviation 8.07 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 4 | -10.7 mm Hg | Standard Deviation 8.2 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 5 | -12.4 mm Hg | Standard Deviation 7.41 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 6 | -12.1 mm Hg | Standard Deviation 7.94 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 7 | -13.1 mm Hg | Standard Deviation 8.74 |
| 2-MET | Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline | Visit 8 | -12.4 mm Hg | Standard Deviation 6.78 |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Summary of Participants that experienced one or more TEAEs by Treatment Group-Safety Population
Time frame: Through study completion (approximately 18 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1-NEB | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 150 Participants |
| 2-MET | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 51 Participants |