Hypertension
Conditions
Keywords
nebivolol, BYSTOLIC ™, hydrochlorothiazide, lisinopril, Prinivil (TM), Zestril (TM), losartan, Cozaar (TM), Impaired Fasting Glucose, Impaired Glucose Tolerance, hypertension
Brief summary
This study is being done to see if the blood pressure and metabolic effects of an approved drug nebivolol is comparable to that of another approved drug hydrochlorothiazide (HCTZ) and placebo in hypertensive patients.
Detailed description
This study is double blind (neither you nor the physician will know when you are receiving placebo, which is an inactive compound such as a sugar pill, or active study drugs nebivolol or hydrochlorothiazide). All participants will also receive lisinopril, an angiotensin converting enzyme, or losartan, an angiotensin receptor blocker. All medications are approved and marketed for the treatment of hypertension.This study is being conducted in about 500 patients at approximately 80 research centers in the United States. The study consists of approximately 9 study visits over a period of 5 months. During these visits, patients will undergo routine health exams and some special laboratory tests such as an oral glucose tolerance test.
Interventions
DRUGNebivolol with concomitant losartan or lisinopril
Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
DRUGHCTZ with concomitant losartan or lisinopril
Encapsulated Hydrochlorothiazide 12.5 mg or 25 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
DRUGPlacebo with concomitant losartan or lisinopril
Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, ambulatory outpatients 18-80 years old at screening. * Have a history of hypertension and taking up to 2 medications for high blood pressure. * Qualifying laboratory results confirming impaired fasting glucose or impaired glucose tolerance * Vision and hearing (hearing aid permissible) sufficient for compliance with questionnaire completion
Exclusion criteria
* Have clinically significant respiratory, liver or cardiovascular disease * Presence of coronary artery disease requiring treatment with a beat blocker, calcium channel blocker or nitrates * Use of niacin or antidiabetic drugs (oral or injectable) within 6 months before study entry * Have a history of hypersensitivity to nebivolol, other beta-blockers, hydrochlorothiazide, or other sulfonamide-derived drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Seated Diastolic Blood Pressure | Change from Baseline Visit 4 (Week 0) To Visit 8 (Week 12) | Change from Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12, Last Observation Carried Forward (LOCF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Glucose Level After an Oral Glucose Tolerance Test | Change from Baseline Visit 3 or 4 (Week -2 or 0) To Visit 8 (Week 12) | Change from Baseline in Plasma Glucose 2 Hours Post-oral Glucose 75 grams, given as part of an Oral Glucose Tolerance Test (OGTT). Last Observation Carried Forward. |
Countries
United States
Participant flow
Recruitment details
May 2008 to March 2010 at 96 US sites, 72 sites randomized patients.
Pre-assignment details
A losartan or lisinopril run-in phase was required for all patients before assignment to Placebo or Nebivolol or Hydrochlorothiazide arms.
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration | 223 |
| Hydrochlorothiazide (HCTZ) Encapsulated Hydrochlorothiazide 12.5 mg or 25 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration. | 212 |
| Placebo Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration. | 102 |
| Total | 537 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 23 | 14 | 2 |
| Overall Study | Lack of Efficacy | 2 | 2 | 2 |
| Overall Study | Lost to Follow-up | 6 | 6 | 5 |
| Overall Study | Participated in two Nebivolol studies | 0 | 0 | 1 |
| Overall Study | Poor compliance | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 6 | 9 | 1 |
| Overall Study | Randomization criteria not met | 0 | 1 | 0 |
| Overall Study | Sponsor Terminated due to PI oversight | 0 | 1 | 0 |
| Overall Study | Unconfirmed pregnancy | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 1 |
Baseline characteristics
| Characteristic | Nebivolol | Hydrochlorothiazide (HCTZ) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 9.6 | 55.7 years STANDARD_DEVIATION 10.4 | 55.2 years STANDARD_DEVIATION 11.3 | 55.1 years STANDARD_DEVIATION 10.3 |
| Age, Customized Patients 18 to 65 years of age | 190 Participants | 172 Participants | 81 Participants | 443 Participants |
| Age, Customized Patients greater than or equal to 65 years of age. | 33 Participants | 40 Participants | 21 Participants | 94 Participants |
| Region of Enrollment United States | 223 Participants | 212 Participants | 102 Participants | 537 Participants |
| Sex: Female, Male Female | 101 Participants | 97 Participants | 38 Participants | 236 Participants |
| Sex: Female, Male Male | 122 Participants | 115 Participants | 64 Participants | 301 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 223 | 21 / 212 | 14 / 102 |
| serious Total, serious adverse events | 5 / 223 | 6 / 212 | 2 / 102 |
Outcome results
Primary
Trough Seated Diastolic Blood Pressure
Change from Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12, Last Observation Carried Forward (LOCF).
Time frame: Change from Baseline Visit 4 (Week 0) To Visit 8 (Week 12)
Population: The between-treatment-group comparison was performed by means of an analysis-of-covariance model with treatment group and study center as factors and baseline value as a covariate based on Intent-to-Treat (ITT) population. As pre-specified in the protocol, the change in seated DBP was performed between the nebivolol and placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol | Trough Seated Diastolic Blood Pressure | -9.4 mm Hg | Standard Deviation 8.9 |
| Placebo | Trough Seated Diastolic Blood Pressure | -5.0 mm Hg | Standard Deviation 9.5 |
Secondary
Plasma Glucose Level After an Oral Glucose Tolerance Test
Change from Baseline in Plasma Glucose 2 Hours Post-oral Glucose 75 grams, given as part of an Oral Glucose Tolerance Test (OGTT). Last Observation Carried Forward.
Time frame: Change from Baseline Visit 3 or 4 (Week -2 or 0) To Visit 8 (Week 12)
Population: The between-treatment-group comparison was performed by means of an analysis-of-covariance model with treatment group and study center as factors and baseline value as a covariate based on Intent-to-Treat (ITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol | Plasma Glucose Level After an Oral Glucose Tolerance Test | 0.20 g/mL | Standard Error 0.19 |
| Placebo | Plasma Glucose Level After an Oral Glucose Tolerance Test | 0.31 g/mL | Standard Error 0.184 |
| Placebo | Plasma Glucose Level After an Oral Glucose Tolerance Test | -0.21 g/mL | Standard Error 0.247 |