Study of the Glycemic Effects of Nebivolol Compared With Metoprolol and HCTZ in Diabetic Hypertensive Patients

Glycemic Effects of Nebivolol Compared With Metoprolol Extended Release and Compared With Hydrochlorothiazide In Hypertensive Patients With Type 2 Diabetes Mellitus: A Pilot Study

This study will evaluate the effects of nebivolol on glycemic control compared with metoprolol and HCTZ in patients with hypertension and type 2 diabetes mellitus

Study Overview

• Status: Completed
• Conditions: Hypertension; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Nebivolol; Drug: Metoprolol ER; Drug: HCTZ

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00717
    • Forest Investigative Site 41
  • Salinas, Puerto Rico, 00751
    • Forest Investigative Site 60
  • Santurce, Puerto Rico, 00909
    • Forest Investigative Site 29
• United States
  • Alabama
    • Athens, Alabama, United States, 35611
      • Forest Investigative Site 15
    • Huntsville, Alabama, United States, 35801
      • Forest Investigative Site 16
  • California
    • Bell Gardens, California, United States, 90201
      • Forest Investigative Site 35
    • Buena Park, California, United States, 90620
      • Forest Investigative Site
    • Chino, California, United States, 91710
      • Forest Investigative Site 54
    • Fremont, California, United States, 94538
      • Forest Investigative Site 40
    • Palm Springs, California, United States, 92262
      • Forest Investigative Site
    • Pomona, California, United States, 91767
      • Forest Investigative Site
    • Sacramento, California, United States, 95821
      • Forest Investigative Site 55
    • San Diego, California, United States, 92128
      • Forest Investigative Site 11
    • Santa Monica, California, United States, 90404
      • Forest Investigative Site
    • Spring Valley, California, United States, 91978
      • Forest Investigative Site
    • Tustin, California, United States, 92780
      • Forest Investigative Site 49
    • Walnut Creek, California, United States, 94598
      • Forest Investigative Site 47
  • Colorado
    • Golden, Colorado, United States, 80401
      • Forest Investigative Site 61
    • Wheat Ridge, Colorado, United States, 80033
      • Forest Investigative Site
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Forest Investigative Site 3
    • DeLand, Florida, United States, 32720
      • Forest Investigative Site 33
    • Hollywood, Florida, United States, 33023
      • Forest Investigative Site 36
    • Miami, Florida, United States, 33135
      • Forest Investigative Site 62
    • Miami, Florida, United States, 33169
      • Forest Investigative Site 080
    • Miami, Florida, United States, 33183
      • Forest Investigative Site 59
    • Pembroke Pines, Florida, United States, 33024
      • Forest Investigative Site 32
    • Pembroke Pines, Florida, United States, 33028
      • Forest Investigative Site 081
    • Tamarac, Florida, United States, 33321
      • Forest Investigative Site 2
    • Tampa, Florida, United States, 33612
      • Forest Investigative Site
    • West Palm Beach, Florida, United States, 33401
      • Forest Investigative Site 19
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Forest Investigative Site 44
    • Augusta, Georgia, United States, 30904
      • Forest Investigative Site 5
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Forest Investigative Site 56
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Forest Investigative Site 57
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Forest Investigative Site 39
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Forest Investigative Site 37
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Forest Investigative Site
    • Baltimore, Maryland, United States, 21209
      • Forest Investigative Site 20
    • Oxon Hill, Maryland, United States, 20745
      • Forest Investigative Site 50
  • Michigan
    • St. Clair Shores, Michigan, United States, 48081
      • Forest Investigative Site 21
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Forest Investigative Site
    • St. Louis, Missouri, United States, 63110
      • Forest Investigative Site
  • New York
    • New Hyde Park, New York, United States, 11042
      • Forest Investigative Site
    • New York, New York, United States, 10032
      • Forest Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Forest Investigative Site 7
    • Charlotte, North Carolina, United States, 28262
      • Forest Investigative Site 45
    • Morehead City, North Carolina, United States, 28557
      • Forest Investigative Site 24
    • Salisbury, North Carolina, United States, 28144
      • Forest Investigative Site 26
    • Wilmington, North Carolina, United States, 28401
      • Forest Investigative Site 18
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Forest Investigative Site 51
    • Cincinnati, Ohio, United States, 45242
      • Forest Investigative Site 48
    • Wadsworth, Ohio, United States, 44281
      • Forest Investigative Site 12
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Forest Investigative Site 17
    • Columbia, South Carolina, United States, 29201
      • Forest Investigative Site 46
    • North Charleston, South Carolina, United States, 29406
      • Forest Investigative Site
    • Simpsonville, South Carolina, United States, 29681
      • Forest Investigative Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Forest Investigative Site 4
  • Tennessee
    • New Tazewell, Tennessee, United States, 37825
      • Forest Investigative Site 10
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Forest Investigative Site 52
    • Dallas, Texas, United States, 75390
      • Forest Investigative Site 28
    • Hurst, Texas, United States, 76054
      • Forest Investigative Site 38
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Forest Investigative Site 34
    • St. George, Utah, United States, 84790
      • Forest Investigative Site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Forest Investigative Site
    • Virginia Beach, Virginia, United States, 23452
      • Forest Investigative Site 31

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

• Male or female, 18-85 years of age
• Blood pressure in the range of 130 to 179/80 to 109 mmHg
• Currently using either an ACE inhibitor or an ARB alone or (an ACE inhibitor or an ARB and up to two other drugs for treatment of high blood pressure). (Patients may be on both an ACE inhibitor and ARB, but would need to be taken off one.)
• Stable medication regimen for high blood pressure for at least one month prior to screening
• Stable type 2 diabetes mellitus for at least 3 months prior to screening that is controlled by any or all of the following: diet and antidiabetic medications that may include fixed-dose insulin
• HgbA1c 6.5 to 8.5% (This is measured at the screening visit)

EXCLUSION CRITERIA:

• Use of any beta blocker within one month prior to screening
• Use of clonidine within 3 months prior to screening
• Diagnosis of hyperthyroidism as evidenced by abnormal lab markers
• Any disorder requiring the intermittent or chronic use of systemic corticosteroids
• Diagnosis of hyperthyroidism as determined by lab markers done at screening
• Active liver disease as determined by lab markers
• Kidney impairment; estimated GFR < 60 mL/min/1.73 m2
• History of heart attack, clinically significant arrhythmia, unstable angina, coronary angioplasty/bypass surgery, stroke, or TIA in 3 months prior to screening
• Chronic heart failure
• Drug or alcohol abuse within 2 years prior to screening
• History of sensitivity to any beta blocker, HCTZ, sulfa drug, or calcium channel blocker
• Participation in another research study within 30 days prior to screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Nebivolol 5 mg (overencapsulated 5-mg marketed tablet), oral administration; Nebivolol 10 mg (overencapsulated 10-mg marketed tablet), oral administration; Nebivolol 20 mg (overencapsulated 20-mg marketed tablet) oral administration; Nebivolol 40 mg (two overencapsulated 20-mg tablets) oral administration; Open-label amlodipine may be given	Drug: Nebivolol; Nebivolol 5 mg (overencapsulated 5-mg marketed tablet), oral administration; Nebivolol 10 mg (overencapsulated 10-mg marketed tablet), oral administration; Nebivolol 20 mg (overencapsulated 20-mg marketed tablet) oral administration; Nebivolol 40 mg (two overencapsulated 20-mg tablets) oral administration; Other Names: Bystolic (TM)
Active Comparator: 2; Metoprolol ER 50 mg (overencapsulated 50-mg tablet) oral administration; Metoprolol ER 100 mg (two overencapsulated 50-mg tablets) oral administration; Metoprolol ER 200 mg (overencapsulated 200-mg tablet) oral administration; Metoprolol ER 400 mg (two overencapsulated 200-mg tablets) oral administration; Open-label amlodipine may be given	Drug: Metoprolol ER; Metoprolol ER 50 mg (overencapsulated 50-mg tablet) oral administration; Metoprolol ER 100 mg (two overencapsulated 50-mg tablets) oral administration; Metoprolol ER 200 mg (overencapsulated 200-mg tablet) oral administration; Metoprolol ER 400 mg (two overencapsulated 200-mg tablets) oral administration
Active Comparator: 3; HCTZ 12.5 mg (overencapsulated 12.5 capsule), oral administration; HCTZ 25 mg (two capsules, overencapsulated 12.5-mg capsules), oral administration; Open-label amlodipine may be given	Drug: HCTZ; HCTZ 12.5 mg (overencapsulated 12.5 capsule), oral administration; HCTZ 25 mg (two capsules, overencapsulated 12.5-mg capsules), oral administration; Other Names: Hydrochlorothorazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Glycosylated Hemoglobin (HbA1c) at Week 26	Change from baseline in glycosylated hemoglobin (HbA1c) over 26 weeks, Last Observation Carried Forward.	visit 5(week 0) and visit 14(week 26)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	Change from Baseline in Insulin Resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at week 26, Last Observation Carried Forward (LOCF). The HOMA-IR is the the product of the blood Glucose and Insulin levels, divided by a constant. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/ml) × fasting plasma glucose (mmol/l) / 22.5	[visit 5(week 0) and visit 14(week 26)]

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Study Director: John Shea, MS, Forest Research Institute, a Subsidiary of Forest Laboratories, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 27, 2008
• First Submitted That Met QC Criteria: August 28, 2008
• First Posted (Estimate): August 29, 2008

Study Record Updates

• Last Update Posted (Estimate): July 29, 2011
• Last Update Submitted That Met QC Criteria: June 30, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Diabetes; Hypertension; nebivolol; Bystolic ™
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-1 Receptor Agonists; Nebivolol; Metoprolol
• Other Study ID Numbers: NEB-MD-19