Trial Outcomes & Findings for Study of the Glycemic Effects of Nebivolol Compared With Metoprolol and HCTZ in Diabetic Hypertensive Patients (NCT NCT00744237)
NCT ID: NCT00744237
Last Updated: 2011-07-29
Results Overview
Change from baseline in glycosylated hemoglobin (HbA1c) over 26 weeks, Last Observation Carried Forward.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
231 participants
Primary outcome timeframe
visit 5(week 0) and visit 14(week 26)
Results posted on
2011-07-29
Participant Flow
Recruitment occured from September 2008 through December 2009 at 69 US sites
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.
Participant milestones
| Measure |
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
* Open-label amlodipine may be given
|
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
* Open-label amlodipine may be given
|
Hydrochlorothiazide (HCTZ)
* 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 Study
STARTED
|
83
|
73
|
74
|
|
Overall Study
COMPLETED
|
56
|
46
|
59
|
|
Overall Study
NOT COMPLETED
|
27
|
27
|
15
|
Reasons for withdrawal
| Measure |
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
* Open-label amlodipine may be given
|
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
* Open-label amlodipine may be given
|
Hydrochlorothiazide (HCTZ)
* 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 Study
Lack of Efficacy
|
1
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
9
|
5
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
1
|
|
Overall Study
Protocol Violation
|
3
|
4
|
3
|
|
Overall Study
Inclusion/Exclusion criteria not met
|
1
|
0
|
0
|
|
Overall Study
Dosing Error
|
1
|
0
|
1
|
|
Overall Study
Study Drug Error
|
1
|
0
|
0
|
|
Overall Study
Prohibited Concomitant Medication
|
0
|
0
|
1
|
|
Overall Study
Poor Compliance
|
0
|
2
|
0
|
|
Overall Study
Administrative. Site Closed
|
1
|
1
|
1
|
|
Overall Study
Adverse Event
|
9
|
13
|
5
|
Baseline Characteristics
Study of the Glycemic Effects of Nebivolol Compared With Metoprolol and HCTZ in Diabetic Hypertensive Patients
Baseline characteristics by cohort
| Measure |
Nebivolol
n=83 Participants
* 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
n=73 Participants
* 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
|
Hydrochlorothiazide (HCTZ)
n=74 Participants
* 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
n=230 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
58.2 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
59.2 years
STANDARD_DEVIATION 8.3 • n=7 Participants
|
59.5 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
58.9 years
STANDARD_DEVIATION 8.9 • n=4 Participants
|
|
Age, Customized
Patients 18 to 64 years of age
|
61 participants
n=5 Participants
|
51 participants
n=7 Participants
|
53 participants
n=5 Participants
|
165 participants
n=4 Participants
|
|
Age, Customized
Patients greater than or equal to 65 years of age.
|
22 participants
n=5 Participants
|
22 participants
n=7 Participants
|
21 participants
n=5 Participants
|
65 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
89 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
53 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
141 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
78 participants
n=5 Participants
|
69 participants
n=7 Participants
|
72 participants
n=5 Participants
|
219 participants
n=4 Participants
|
|
Region of Enrollment
Puerto Rico
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
2 participants
n=5 Participants
|
11 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: visit 5(week 0) and visit 14(week 26)Change from baseline in glycosylated hemoglobin (HbA1c) over 26 weeks, Last Observation Carried Forward.
Outcome measures
| Measure |
Nebivolol
n=77 Participants
* 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
n=69 Participants
* 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
|
Hydrochlorothiazide (HCTZ)
n=68 Participants
* 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
|
|---|---|---|---|
|
Change From Baseline in Mean Glycosylated Hemoglobin (HbA1c) at Week 26
|
0.12 Percentage
Standard Deviation 0.78
|
0.00 Percentage
Standard Deviation 0.65
|
0.40 Percentage
Standard Deviation 0.96
|
SECONDARY outcome
Timeframe: [visit 5(week 0) and visit 14(week 26)]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
Outcome measures
| Measure |
Nebivolol
n=77 Participants
* 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
n=69 Participants
* 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
|
Hydrochlorothiazide (HCTZ)
n=68 Participants
* 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
|
|---|---|---|---|
|
Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
|
0.011 Unit on a scale
Standard Deviation 9.828
|
1.156 Unit on a scale
Standard Deviation 9.628
|
-0.662 Unit on a scale
Standard Deviation 10.178
|
Adverse Events
Nebivolol
Serious events: 2 serious events
Other events: 19 other events
Deaths: 0 deaths
Metoprolol ER
Serious events: 3 serious events
Other events: 17 other events
Deaths: 0 deaths
Hydrochlorothiazide (HCTZ)
Serious events: 2 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Nebivolol
n=83 participants at risk
* 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
n=73 participants at risk
* 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
|
Hydrochlorothiazide (HCTZ)
n=74 participants at risk
* 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
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Cardiac disorders
Arrhythmia
|
1.2%
1/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Cardiac disorders
Cardiomegaly
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Injury, poisoning and procedural complications
Deep vain thrombosis postoperative
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Infections and infestations
Diverticulitis
|
1.2%
1/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Infections and infestations
Incision site cellulitis
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
Other adverse events
| Measure |
Nebivolol
n=83 participants at risk
* 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
n=73 participants at risk
* 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
|
Hydrochlorothiazide (HCTZ)
n=74 participants at risk
* 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
|
|---|---|---|---|
|
Cardiac disorders
Bradycardia
|
7.2%
6/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
11.0%
8/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
0.00%
0/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.6%
3/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
8.2%
6/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Nervous system disorders
Dizziness
|
6.0%
5/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
4.1%
3/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
4.1%
3/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
General disorders
Fatigue
|
3.6%
3/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
6.8%
5/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Nervous system disorders
Headache
|
6.0%
5/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
9.6%
7/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
6.8%
5/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.2%
1/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
6.8%
5/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Infections and infestations
Nasopharyngitis
|
2.4%
2/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
5.5%
4/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
4.1%
3/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
General disorders
Oedema peripheral
|
9.6%
8/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
9.6%
7/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
8.1%
6/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
|
Infections and infestations
Upper Resiratory tract infection
|
2.4%
2/83 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
1.4%
1/73 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
6.8%
5/74 • Adverse Events were reported over a 12-month period, from September 2008 to August 2010.
|
Additional Information
Noah Rosenberg , MD, Exec. Dir, Clin Dev, Cardiovascular and Metabolism
Forest Laboratories, Inc
Phone: 2014278000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER