Efficacy and Safety Study to Evaluate Combination Therapy With Nebivolol and Lisinopril vs. Placebo and Monotherapy in Patients With Stage 2 Diastolic Hypertension

A Randomized, Double-blind, Parallel-Group Study to Evaluate the Effects of First-Line Treatment With a Free Combination of Nebivolol and Lisinopril Compared With Placebo and the Monotherapy Components on Blood Pressure in Patients With Stage 2 Diastolic Hypertension

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).

Study Overview

• Status: Completed
• Conditions: Stage 2 Diastolic Hypertension
• Intervention / Treatment: Drug: nebivolol and lisinopril (free combination); Drug: nebivolol monotherapy; Drug: lisinopril monotherapy; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 664
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Forest Investigative Site 044
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85254
      • Forest Investigative Site #58
    • Tempe, Arizona, United States, 85282
      • Forest Investigative Site 080
    • Tucson, Arizona, United States, 85741
      • Forest Investigative Site 096
  • California
    • Buena Park, California, United States, 90620
      • Forest Investigative Site 038
    • Burbank, California, United States, 91505
      • Forest Investigative Site 075
    • Costa Mesa, California, United States, 92626
      • Forest Investigative Site 042
    • Fountain Valley, California, United States, 92708
      • Forest Investigative Site 028
    • Fresno, California, United States, 93726
      • Forest Investigative Site 064
    • Lancaster, California, United States, 93539
      • Forest Investigative Site 079
    • Long Beach, California, United States, 90806
      • Forest Investigative Site 097
    • Los Angeles, California, United States, 90057
      • Forest Investigative Site 049
    • Riverside, California, United States, 92506
      • Forest Investigative Site 081
    • San Marino, California, United States, 91108
      • Forest Investigative Site 040
    • San Ramon, California, United States, 94583
      • Forest Investigative Site 059
    • Santa Ana, California, United States, 92705
      • Forest Investigative Site 074
    • Tustin, California, United States, 92780
      • Forest Investigative Site 072
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Forest Investigative Site 077
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Forest Investigative Site 050
  • Florida
    • Boca Raton, Florida, United States, 33432
      • Forest Investigative Site 019
    • Brandon, Florida, United States, 33511
      • Forest Investigative Site 056
    • Brooksville, Florida, United States, 34601
      • Forest Investigative Site 043
    • Fort Lauderdale, Florida, United States, 33306
      • Forest Investigative Site 035
    • Hialeah, Florida, United States, 33012
      • Forest Investigative Site 002
    • Miami, Florida, United States, 33014
      • Forest Investigative Site 003
    • Miami, Florida, United States, 33133
      • Forest Investigative Site 067
    • Miami, Florida, United States, 33143
      • Forest Investigative Site 057
    • Miami, Florida, United States, 33169
      • Forest Investigative Site 068
    • Miami, Florida, United States, 33183
      • Forest Investigative Site 007
    • New Port Richey, Florida, United States, 34652
      • Forest Investigative Site 009
    • Pembroke Pines, Florida, United States, 33024
      • Forest Investigative Site 036
    • Pembroke Pines, Florida, United States, 33028
      • Forest Investigative Site 005
    • St. Petersburg, Florida, United States, 33709
      • Forest Investigative Site 001
    • Tampa, Florida, United States, 33606
      • Forest Investigative Site 004
    • Tampa, Florida, United States, 33614
      • Forest Investigative Site 046
  • Georgia
    • Atlanta, Georgia, United States, 30338
      • Forest Investigative Site 076
    • Stockbridge, Georgia, United States, 30281
      • Forest Investigative Site 055
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Forest Investigative Site 070
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Forest Investigative Site 008
  • Illinois
    • Chicago, Illinois, United States, 60490
      • Forest Investigative Site 016
    • Chicago, Illinois, United States, 60607
      • Forest Investigative Site 085
    • Chicago, Illinois, United States, 60611
      • Forest Investigative Site 082
    • Morton, Illinois, United States, 61550
      • Forest Investigative Site 039
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Forest Investigative Site 087
    • Madisonville, Kentucky, United States, 42431
      • Forest Investigative Site 099
    • Owensboro, Kentucky, United States, 42303
      • Forest Investigative Site 060
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Forest Investigative Site 030
  • Maryland
    • Balitmore, Maryland, United States, 21209
      • Forest Investigative Site 069
    • Baltimore, Maryland, United States, 21236
      • Forest Investigative Site 014
    • Baltimore, Maryland, United States, 21204
      • Forest Investigative Site 021
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Forest Investigative Site 054
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • Forest Investigative Site 095
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Forest Investigative Site 010
    • Las Vegas, Nevada, United States, 89106
      • Forest Investigative Site 012
  • New Jersey
    • Elizabeth, New Jersey, United States, 07202
      • Forest Investigative Site 020
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Forest Investigative Site 065
    • Charlotte, North Carolina, United States, 28204
      • Forest Investigative Site 034
    • Charlotte, North Carolina, United States, 28209
      • Forest Investigative Site 086
    • Hickory, North Carolina, United States, 28601
      • Forest Investigative Site 089
    • Hickory, North Carolina, United States, 28602
      • Forest Investigative Site 094
    • Lenoir, North Carolina, United States, 28645
      • Forest Investigative Site 027
    • Raleigh, North Carolina, United States, 27609
      • Forest Investigative Site 101
    • Raleigh, North Carolina, United States, 27612
      • Forest Investigative Site 024
    • Shelby, North Carolina, United States, 28150
      • Forest Investigative Site 013
    • Winston-Salem, North Carolina, United States, 27103
      • Forest Investigative Site 022
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Forest Investigative Site 098
    • Columbus, Ohio, United States, 43213
      • Forest Investigative Site 084
    • Dayton, Ohio, United States, 45406
      • Forest Investigative Site 026
    • Zanesville, Ohio, United States, 43701
      • Forest Investigative Site 051
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Forest Investigative Site 053
  • Oregon
    • Ashland, Oregon, United States, 97520
      • Forest Investigative Site 062
  • Pennsylvania
    • Broomall, Pennsylvania, United States, 19008
      • Forest Investigative Site 011
    • Philadelphia, Pennsylvania, United States, 19146
      • Forest Investigative Site 061
    • Tipton, Pennsylvania, United States, 16684
      • Forest Investigative Site 015
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • Forest Investigative Site 045
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Forest Investigative Site 066
    • Greer, South Carolina, United States, 29651
      • Forest Investigative Site 048
    • Mount Pleasant, South Carolina, United States, 49464
      • Forest Investigative Site 093
  • Tennessee
    • Fayetteville, Tennessee, United States, 37334
      • Forest Investigative Site 052
  • Texas
    • Carrollton, Texas, United States, 75006
      • Forest Investigative Site 025
    • Houston, Texas, United States, 77074
      • Forest Investigative Site 006
    • Houston, Texas, United States, 77074
      • Forest Investigative Site 029
    • San Antonio, Texas, United States, 78229
      • Forest Investigative Site 071
    • San Antonio, Texas, United States, 78205
      • Forest Investigative Site 047
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Forest Investigative Site 018
    • Salt Lake City, Utah, United States, 84124
      • Forest Investigative Site 100
    • St. George, Utah, United States, 84790
      • Forest Investigative Site 023
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Forest Investigative Site 031
    • Norfolk, Virginia, United States, 23510
      • Forest Investigative Site 041
  • Washington
    • Tacoma, Washington, United States, 98405
      • Forest Investigative Site 078

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Combination group - starting dose level nebivolol 5mg and lisinopril 10mg	Drug: nebivolol 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
Active Comparator: 2; Nebivolol monotherapy group - starting dose level nebivolol 5mg	Drug: nebivolol 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
Active Comparator: 3; Lisinopril monotherapy group - starting dose level lisinopril 10mg	Drug: lisinopril 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
Placebo Comparator: 4; Placebo group - starting dose is placebo	Drug: placebo; Placebo tablet, oral administration/QD/oral administration/up to 12 weeks Placebo capsule, oral administration/QD/oral administration/up to 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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)

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Study Director: Manfred Stapff, MD PhD, Forest Laboratories

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: October 7, 2010
• First Submitted That Met QC Criteria: October 8, 2010
• First Posted (Estimate): October 11, 2010

Study Record Updates

• Last Update Posted (Estimate): June 21, 2012
• Last Update Submitted That Met QC Criteria: May 18, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Agonists; Adrenergic beta-1 Receptor Agonists; Nebivolol; Lisinopril
• Other Study ID Numbers: NEB-MD-25