Hypertension
Conditions
Keywords
Hypertension, Nebivolol, Beta blocker, Tolerability
Brief summary
The purpose of this study was to compare the tolerability of nebivolol to metoprolol ER in a general population of patients with mild to moderate hypertension receiving hydrochlorothiazide (HCTZ)
Detailed description
This study was an 18-week study to evaluate the tolerability of nebivolol compared to metoprolol ER in outpatients with mild to moderate hypertension taking HCTZ. It is a multi-center, randomized, double blind (DB), active-control, parallel-group study, starting with a 4-week HCTZ run-in phase, followed by a 12-week DB treatment phase. Patients meeting the entry criteria at the end of run-in are randomized to one of two treatment groups, nebivolol or metoprolol ER. Up-titration of dose of study drug will occur if needed during the first 4 weeks of the DB phase, after which there is an 8-week stable-dose period of treatment. A 2-week double-blind withdrawal phase follows, during which tapering off study drug occurs.
Interventions
DRUGNebivolol
Nebivolol once daily, oral administration
DRUGMetoprolol ER
Metoprolol ER once daily, oral administration
Sponsors
Mylan Laboratories
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, ambulatory outpatients * History of hypertension being treated with two medications, one of which must be HCTZ and the other of which must not be a beta-blocker or clonidine * SBP of 135-155 mm Hg and/or DBP of \>85 mm Hg at screening (Visit 1) * SBP of 140-165 mm Hg and DBP \> 90 mmHg at randomization (Visit 3)
Exclusion criteria
* Treatment with a beta-blocker or clonidine within 6 months of screening (Visit 1) * Clinically significant respiratory disease (e.g., bronchial asthma, reactive airways disease, chronic obstructive pulmonary disease) * Coronary artery disease requiring treatment with a calcium channel blocker or nitrates * Clinically significant cardiovascular disease (e.g., myocardial infarction, cerebrovascular event, significant arrhythmia) within 6 months of screening (Visit 1) * History of severe mental illness (including Major Depressive Disorder, psychosis, dementia, bipolar disorder) within 6 months of screening (Visit 1) * Use of antipsychotic medication (e.g., dopamine receptor antagonists, serotonin dopamine receptor antagonists) or antidepressants * Diabetes mellitus, type I or II * Participation in a previous investigational study of nebivolol at any time * Receipt of treatment with an investigational study drug within 30 days of screening (Visit 1) * History of hypersensitivity to nebivolol, metoprolol ER, other beta-blockers, HCTZ, or other sulfonamide-derived drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Patient Symptoms Questionnaire (PSQ) Derived Score | Measurements occured over a 14 week period, from Visit 2 (Week -2) to Visit 10 (Week 12) | The PSQ contained 44 possible symptoms rated from 0 (no discomfort) to 5 (extreme discomfort). |
Secondary
| Measure | Time frame |
|---|---|
| Peripheral Blood Pressure (BP) | Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14) |
| Pulse Rate | Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14) |
Countries
United States
Participant flow
Recruitment details
Patient recruitment occurred over a four month period from October 2007 to January 2008 at 39 US sites.
Pre-assignment details
All patients went through a 4 week hydrochlorothiazide (HCTZ) run-in phase before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Nebivolol 5 mg, 10 mg or 20 mg | 25 |
| Metoprolol Extended-Release (ER) Metoprolol ER 50 mg, 100 mg or 200 mg | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not Meet Entry Criteria | 0 | 2 |
| Overall Study | Study was Administratively Terminated | 25 | 24 |
Baseline characteristics
| Characteristic | Metoprolol Extended-Release (ER) | Nebivolol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 22 Participants | 41 Participants |
| Age, Continuous | 57.0 years STANDARD_DEVIATION 9.32 | 55.0 years STANDARD_DEVIATION 8.67 | 56.0 years STANDARD_DEVIATION 8.95 |
| Region of Enrollment United States | 24 Participants | 25 Participants | 49 Participants |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 26 |
| other Total, other adverse events | 5 / 25 | 3 / 24 |
| serious Total, serious adverse events | 0 / 25 | 0 / 26 |
Outcome results
Primary
Change From Baseline in the Patient Symptoms Questionnaire (PSQ) Derived Score
The PSQ contained 44 possible symptoms rated from 0 (no discomfort) to 5 (extreme discomfort).
Time frame: Measurements occured over a 14 week period, from Visit 2 (Week -2) to Visit 10 (Week 12)
Population: Formal analysis of the primary endpoint was not conducted in this abbreviated study as the study was terminated before visit 10 was reached.
Secondary
Peripheral Blood Pressure (BP)
Time frame: Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14)
Population: Formal analysis of the secondary endpoint was not conducted in this abbreviated study as the study was terminated before all visits were completed. No patients completed the study.
Secondary
Pulse Rate
Time frame: Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14)
Population: Formal analysis of the secondary endpoint was not conducted in this abbreviated study as the study was terminated before all visits were completed. No patients completed the study.