Stage 2 Diastolic Hypertension
Conditions
Brief summary
This study will evaluate the safety and efficacy of first-line treatment with a free combination (as two separate pills) of nebivolol and lisinopril in patients with stage 2 diastolic hypertension (DBP\>= 100 mmHg).
Interventions
DRUGnebivolol and lisinopril (free combination)
nebivolol 5-mg and lisinopril 10-mg (nebivolol non-trade 5-mg tablet and overencapsulated lisinopril 10-mg tablet)/QD/oral administration/up to 12 weeks nebivolol 20-mg and lisinopril 40-mg (nebivolol non-trade 20-mg tablet and overencapsulated lisinopril 40-mg tablet)/QD/oral administration/up to 10 weeks nebivolol 5-mg and lisinopril 40-mg (nebivolol non-trade 5-mg tablet and overencapsulated lisinopril 40-mg tablet)/QD/oral administration/up to 6 weeks nebivolol 20-mg and lisinopril 10-mg (nebivolol non-trade 20-mg tablet and overencapsulated lisinopril 10-mg tablet/QD/oral administration/up to 6 weeks
DRUGnebivolol monotherapy
nebivolol 5-mg (non-trade 5-mg tablet)/QD/oral administration/up to 12 weeks nebivolol 10-mg (non-trade 10-mg tablet/QD/oral administration/for 1-week down-titration period only) nebivolol 20-mg (non-trade 20-mg tablet)/QD/oral administration/up to 10 weeks
DRUGlisinopril monotherapy
lisinopril 10-mg (overencapsulated 10-mg tablet)/QD/oral administration/up to 12 weeks lisinopril 40-mg (overencapsulated 40-mg tablet)/QD/oral administration/up to 10 weeks
DRUGplacebo
Placebo tablet, oral administration/QD/oral administration/up to 12 weeks Placebo capsule, oral administration/QD/oral administration/up to 12 weeks
Sponsors
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 64 Years
Healthy volunteers
No
Inclusion criteria
* male and female outpatients 18 to 64 years of age * Females must be post-menopausal, or not pregnant and using an approved contraceptive regimen * stage 2 diastolic hypertension (DBP \>= 100 mmHg)
Exclusion criteria
* secondary hypertension * evidence of other concurrent disease or conditions that might interfere with the conduct of the study * participation in an investigational drug study within 30 days or 5 half-lives, whichever is longer, of Screening (Visit 1). * have a history of hypersensitivity to nebivolol or other β-blockers, or any contraindication to β-blocker use
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6. | Visit 6/(Week 0) and Visit 9/(Week 6) |
Secondary
| Measure | Time frame |
|---|---|
| The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6. | Visit 6/(Week 0) and Visit 9/(Week 6) |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
664 patients were randomized to receive double-blind treatment; 661 patients received at least 1 dose of double-blind treatment (Safety Population); and 656 patients had at least 1 postbaseline assessment of trough seated DBP (ITT Population)
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo group - starting dose is placebo | 95 |
| Nebivolol + Lisinopril (Combination) Combination group - starting dose level nebivolol 5mg and lisinopril 10mg | 189 |
| Nebivolol Nebivolol monotherapy group - starting dose level nebivolol 5mg | 188 |
| Lisinopril Lisinopril monotherapy group - starting dose level lisinopril 10mg | 189 |
| Total | 661 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 | 6 | 7 |
| Overall Study | Did not meet InclusionExclusion criteria | 1 | 1 | 1 | 2 |
| Overall Study | Lack of Efficacy | 9 | 6 | 5 | 12 |
| Overall Study | Lost to Follow-up | 3 | 8 | 2 | 1 |
| Overall Study | Other Reason | 2 | 2 | 6 | 4 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 2 | 6 | 7 |
Baseline characteristics
| Characteristic | Nebivolol + Lisinopril (Combination) | Nebivolol | Placebo | Lisinopril | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 189 Participants | 188 Participants | 95 Participants | 189 Participants | 661 Participants |
| Age Continuous | 48.8 years STANDARD_DEVIATION 8.4 | 49.7 years STANDARD_DEVIATION 8.4 | 47.4 years STANDARD_DEVIATION 9.7 | 50.1 years STANDARD_DEVIATION 8 | 49.2 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 189 participants | 188 participants | 95 participants | 189 participants | 661 participants |
| Sex: Female, Male Female | 75 Participants | 82 Participants | 47 Participants | 74 Participants | 278 Participants |
| Sex: Female, Male Male | 114 Participants | 106 Participants | 48 Participants | 115 Participants | 383 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 95 | 31 / 189 | 32 / 188 | 24 / 189 |
| serious Total, serious adverse events | 2 / 95 | 2 / 189 | 3 / 188 | 4 / 189 |
Outcome results
Primary
The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6.
Time frame: Visit 6/(Week 0) and Visit 9/(Week 6)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6. | -8.0 mm HG | Standard Deviation 9.2 |
| Nebivolol + Lisinopril (Combination) | The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6. | -17.2 mm HG | Standard Deviation 10.2 |
| Nebivolol | The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6. | -13.3 mm HG | Standard Deviation 8.9 |
| Lisinopril | The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6. | -12.0 mm HG | Standard Deviation 9.8 |
Secondary
The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6.
Time frame: Visit 6/(Week 0) and Visit 9/(Week 6)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6. | -9.9 mm HG | Standard Deviation 16.4 |
| Nebivolol + Lisinopril (Combination) | The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6. | -19.2 mm HG | Standard Deviation 19.8 |
| Nebivolol | The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6. | -14.4 mm HG | Standard Deviation 14.1 |
| Lisinopril | The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6. | -16.1 mm HG | Standard Deviation 17.2 |