Study to Evaluate Symptoms in Patients Treated With Nebivolol or Metoprolol Extended-release (ER) for Hypertension

Study Overview
=================
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.

Official Title
-----------------
Tolerability of Nebivolol Compared With Metoprolol ER in Patients With Mild to Moderate Hypertension Taking Hydrochlorothiazide (HCTZ)

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: Metoprolol ER
* Drug: Nebivolol


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nebivolol<br>Nebivolol 5 mg, 10 mg or 20 mg | Drug: Nebivolol<br>* Nebivolol once daily, oral administration<br>|
| Active Comparator: Metoprolol ER<br>Metoprolol ER 50 mg, 100 mg or 200 mg | Drug: Metoprolol ER<br>* Metoprolol ER once daily, oral administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Measurements occured over a 14 week period, from Visit 2 (Week -2) to Visit 10 (Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypertension, Nebivolol, Beta blocker, Tolerability