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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00744237
Recruitment Status : Completed
First Posted : August 29, 2008
Results First Posted : July 29, 2011
Last Update Posted : July 29, 2011
Sponsor:
Information provided by:
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Hypertension
Type 2 Diabetes Mellitus
Interventions Drug: Nebivolol
Drug: Metoprolol ER
Drug: HCTZ
Enrollment 231
Recruitment Details Recruitment occured from September 2008 through December 2009 at 69 US sites
Pre-assignment Details Placebo washout phase was required for patients currently on any anti-hypertensives at screening exclusive of background ACE inhibitor or ARB before assignment to HCTZ or Metoprolol ER or Nebivolol arms.
Arm/Group Title Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ)
Hide Arm/Group Description
  • 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
  • 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
  • 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
Period Title: Overall Study
Started 83 73 74
Completed 56 46 59
Not Completed 27 27 15
Reason Not Completed
Lack of Efficacy             1             1             0
Withdrawal by Subject             9             5             3
Lost to Follow-up             1             1             1
Protocol Violation             3             4             3
Inclusion/Exclusion criteria not met             1             0             0
Dosing Error             1             0             1
Study Drug Error             1             0             0
Prohibited Concomitant Medication             0             0             1
Poor Compliance             0             2             0
Administrative. Site Closed             1             1             1
Adverse Event             9             13             5
Arm/Group Title Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ) Total
Hide Arm/Group Description
  • 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
  • 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
  • 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
Total of all reporting groups
Overall Number of Baseline Participants 83 73 74 230
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 83 participants 73 participants 74 participants 230 participants
58.2  (9.3) 59.2  (8.3) 59.5  (9.0) 58.9  (8.9)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 83 participants 73 participants 74 participants 230 participants
Patients 18 to 64 years of age 61 51 53 165
Patients greater than or equal to 65 years of age. 22 22 21 65
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 73 participants 74 participants 230 participants
Female
30
  36.1%
30
  41.1%
29
  39.2%
89
  38.7%
Male
53
  63.9%
43
  58.9%
45
  60.8%
141
  61.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 83 participants 73 participants 74 participants 230 participants
United States 78 69 72 219
Puerto Rico 5 4 2 11
1.Primary Outcome
Title Change From Baseline in Mean Glycosylated Hemoglobin (HbA1c) at Week 26
Hide Description Change from baseline in glycosylated hemoglobin (HbA1c) over 26 weeks, Last Observation Carried Forward.
Time Frame visit 5(week 0) and visit 14(week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ)
Hide Arm/Group Description:
  • 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
  • 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
  • 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
Overall Number of Participants Analyzed 77 69 68
Mean (Standard Deviation)
Unit of Measure: Percentage
0.12  (0.78) 0.00  (0.65) 0.40  (0.96)
2.Secondary Outcome
Title Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Hide Description 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
Time Frame [visit 5(week 0) and visit 14(week 26)]
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ)
Hide Arm/Group Description:
  • 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
  • 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
  • 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
Overall Number of Participants Analyzed 77 69 68
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
0.011  (9.828) 1.156  (9.628) -0.662  (10.178)
Time Frame Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ)
Hide Arm/Group Description
  • 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
  • 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
  • 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
All-Cause Mortality
Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/83 (2.41%)   3/73 (4.11%)   2/74 (2.70%) 
Cardiac disorders       
Arrhythmia  1  1/83 (1.20%)  0/73 (0.00%)  0/74 (0.00%) 
Cardiomegaly  1  0/83 (0.00%)  1/73 (1.37%)  0/74 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  0/83 (0.00%)  0/73 (0.00%)  1/74 (1.35%) 
Infections and infestations       
Diverticulitis  1  1/83 (1.20%)  0/73 (0.00%)  0/74 (0.00%) 
Incision site cellulitis  1  0/83 (0.00%)  1/73 (1.37%)  0/74 (0.00%) 
Injury, poisoning and procedural complications       
Deep vain thrombosis postoperative  1  0/83 (0.00%)  1/73 (1.37%)  0/74 (0.00%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc degeneration  1  0/83 (0.00%)  1/73 (1.37%)  0/74 (0.00%) 
Osteoarthritis  1  0/83 (0.00%)  1/73 (1.37%)  0/74 (0.00%) 
Spinal column stenosis  1  0/83 (0.00%)  1/73 (1.37%)  0/74 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer metastatic  1  0/83 (0.00%)  0/73 (0.00%)  1/74 (1.35%) 
Respiratory, thoracic and mediastinal disorders       
Pneumonia aspiration  1  0/83 (0.00%)  1/73 (1.37%)  0/74 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nebivolol Metoprolol ER Hydrochlorothiazide (HCTZ)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   19/83 (22.89%)   17/73 (23.29%)   17/74 (22.97%) 
Cardiac disorders       
Bradycardia  1  6/83 (7.23%)  8/73 (10.96%)  0/74 (0.00%) 
General disorders       
Fatigue  1  3/83 (3.61%)  1/73 (1.37%)  5/74 (6.76%) 
Oedema peripheral  1  8/83 (9.64%)  7/73 (9.59%)  6/74 (8.11%) 
Infections and infestations       
Nasopharyngitis  1  2/83 (2.41%)  4/73 (5.48%)  3/74 (4.05%) 
Upper Resiratory tract infection  1  2/83 (2.41%)  1/73 (1.37%)  5/74 (6.76%) 
Metabolism and nutrition disorders       
Hyperglycaemia  1  1/83 (1.20%)  1/73 (1.37%)  5/74 (6.76%) 
Nervous system disorders       
Dizziness  1  5/83 (6.02%)  3/73 (4.11%)  3/74 (4.05%) 
Headache  1  5/83 (6.02%)  7/73 (9.59%)  5/74 (6.76%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  3/83 (3.61%)  6/73 (8.22%)  1/74 (1.35%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

All data generated in this study will be the property of Forest Research Institute. An integrated clinical and statistical report will be prepared at the completion of the study.

Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute.

Results Point of Contact
Name/Title: Noah Rosenberg , MD, Exec. Dir, Clin Dev, Cardiovascular and Metabolism
Organization: Forest Laboratories, Inc
Phone: 2014278000 ext 2133
Responsible Party: John Whalen, MD, Executive Director, Clinical Development, Cardiovascular, Forest Research Institute, a Subsidiary of Forest Laboratories Inc.
ClinicalTrials.gov Identifier: NCT00744237     History of Changes
Other Study ID Numbers: NEB-MD-19
First Submitted: August 27, 2008
First Posted: August 29, 2008
Results First Submitted: June 30, 2011
Results First Posted: July 29, 2011
Last Update Posted: July 29, 2011