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

This study is 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. Uptitration 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.

Inclusion Criteria:

- Male or female, ambulatory outpatients 18-80 yo. Females must be post-menopausal, or
not pregnant and using an approved contraceptive regimen

- 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

- Vision and hearing (hearing aid permissable) sufficient for compliance with testing
procedures (i.e., with phone- and/or internet-based assessments)

Exclusion Criteria:

- Treatment with a beta-blocker or clonidine within 6 months of Screening

- 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

- Cardiovascular disease (e.g., myocardial infarction, cerebrovascular event,
significant arrhythmia) within 6 months of screening

- History of severe mental illness (including Major Depressive Disorder, psychosis,
dementia, bipolar disorder) within 6 months of screening

- Use of antipsychotic medicaiton (e.g., dopanine 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

- History of hypersensitivity to nebivolol, metoprolol ER, other beta-blockers, HCTZ, or
other sulfonamide-derived drugs