The Blood Pressure and Metabolic Effects of Nebivolol in Hypertensive Patients With Impaired Glucose Tolerance or Impaired Fasting Glucose

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00673790
• Collaborator: (none)
• Enrollment: 537
• Locations: 88
• Arms: 3
• Actual Duration (Months): 25.8
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is being done to see if the blood pressure and metabolic effects of an approved drug nebivolol is comparable to that of another approved drug hydrochlorothiazide (HCTZ) and placebo in hypertensive patients.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Nebivolol with concomitant losartan or lisinopril; Drug: HCTZ with concomitant losartan or lisinopril; Drug: Placebo with concomitant losartan or lisinopril	Phase 4

Detailed Description

This study is double blind (neither you nor the physician will know when you are receiving placebo, which is an inactive compound such as a sugar pill, or active study drugs nebivolol or hydrochlorothiazide).

All participants will also receive lisinopril, an angiotensin converting enzyme, or losartan, an angiotensin receptor blocker. All medications are approved and marketed for the treatment of hypertension.This study is being conducted in about 500 patients at approximately 80 research centers in the United States.

The study consists of approximately 9 study visits over a period of 5 months. During these visits, patients will undergo routine health exams and some special laboratory tests such as an oral glucose tolerance test.

Study Design

• Study Type: Interventional
• Actual Enrollment: 537 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Blood Pressure and Metabolic Effects of Nebivolol Compared With Hydrochlorothiazide and Placebo in Hypertensive Patients With Impaired Glucose Tolerance or Impaired Fasting Glucose
• Actual Study Start Date: May 15, 2008
• Actual Primary Completion Date: Jul 9, 2010
• Actual Study Completion Date: Jul 9, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nebivolol Nebivolol with concomitant losartan or lisinopril	Drug: Nebivolol with concomitant losartan or lisinopril; Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
Active Comparator: Hydrochlorothiazide (HCTZ) HCTZ with concomitant losartan or lisinopril	Drug: HCTZ with concomitant losartan or lisinopril; Encapsulated Hydrochlorothiazide 12.5 mg or 25 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
Placebo Comparator: Placebo Placebo with concomitant losartan or lisinopril	Drug: Placebo with concomitant losartan or lisinopril; Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.

Outcome Measures

Primary Outcome Measures

1. Trough Seated Diastolic Blood Pressure [Change from Baseline Visit 4 (Week 0) To Visit 8 (Week 12)]

   Change from Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12, Last Observation Carried Forward (LOCF).

Secondary Outcome Measures

1. Plasma Glucose Level After an Oral Glucose Tolerance Test [Change from Baseline Visit 3 or 4 (Week -2 or 0) To Visit 8 (Week 12)]

   Change from Baseline in Plasma Glucose 2 Hours Post-oral Glucose 75 grams, given as part of an Oral Glucose Tolerance Test (OGTT). Last Observation Carried Forward.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, ambulatory outpatients 18-80 years old at screening.

• Have a history of hypertension and taking up to 2 medications for high blood pressure.

• Qualifying laboratory results confirming impaired fasting glucose or impaired glucose tolerance

• Vision and hearing (hearing aid permissible) sufficient for compliance with questionnaire completion

Exclusion Criteria:

• Have clinically significant respiratory, liver or cardiovascular disease

• Presence of coronary artery disease requiring treatment with a beat blocker, calcium channel blocker or nitrates

• Use of niacin or antidiabetic drugs (oral or injectable) within 6 months before study entry

• Have a history of hypersensitivity to nebivolol, other beta-blockers, hydrochlorothiazide, or other sulfonamide-derived drugs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 058	Athens	Alabama	United States	35611
2	Forest Investigative Site 101	Birmingham	Alabama	United States	35215
3	Forest Investigative Site 016	Huntsville	Alabama	United States	35801
4	Forest Investigative Site 119	Phoenix	Arizona	United States	85020
5	Forest Investigative Site 078	Tucson	Arizona	United States	85715
6	Forest Investigative Site 056	Anaheim	California	United States	92801
7	Forest Investigative Site 097	Bell Gardens	California	United States	90201
8	Forest Investigative Site 026	Buena Park	California	United States	90620
9	Forest Investigative Site 147	Buena Park	California	United States	90620
10	Forest Investigative Site 061	Chino	California	United States	91710
11	Forest Investigative Site 108	Costa Mesa	California	United States	92626
12	Forest Investigative Site 054	Encinitas	California	United States	92024
13	Forest Investigative Site 128	Fresno	California	United States	93703
14	Forest Investigative Site 127	Huntington Park	California	United States	90255
15	Forest Investigative Site 030	Long Beach	California	United States	90806
16	Forest Investigative Site 085	Los Angeles	California	United States	90057
17	Forest Investigative Site 028	Los Angeles	California	United States	90211
18	Forest Investigative Site 124	National City	California	United States	91950
19	Forest Investigative Site 117	Riverside	California	United States	92506
20	Forest Investigative Site 025	Roseville	California	United States	95661
21	Forest Investigative Site 017	Sacramento	California	United States	95821
22	Forest Investigative Site 068	San Diego	California	United States	92128
23	Forest Investigative Site 112	Santa Ana	California	United States	92705
24	Forest Investigative Site 063	Temecula	California	United States	92591
25	Forest Investigative Site 013	Tustin	California	United States	92780
26	Forest Investigative Site 052	Walnut Creek	California	United States	94598
27	Forest Investigative Site 074	Milford	Connecticut	United States	06460
28	Forest Investigative Site 139	Brooksville	Florida	United States	34601
29	Forest Investigative Site 103	Coral Gables	Florida	United States	33134
30	Forest Investigative Site 019	Daytona Beach	Florida	United States	32117
31	Forest Investigative Site 010	DeLand	Florida	United States	32720
32	Forest Investigative Site 073	Hialeah	Florida	United States	33012
33	Forest Investigative Site 109	Hialeah	Florida	United States	33012
34	Forest Investigative Site 036	Hollywood	Florida	United States	33023
35	Forest Investigative Site 104	Miami	Florida	United States	33135
36	Forest Investigative Site 121	Miami	Florida	United States	33143
37	Forest Investigative Site 099	Miami	Florida	United States	33183
38	Forest Investigative Site 107	Pembroke Pines	Florida	United States	33024
39	Forest Investigative Site 141	Saint Petersburg	Florida	United States	33709
40	Forest Investigative Site 140	Tampa	Florida	United States	33606
41	Forest Investigative Site 060	West Palm Beach	Florida	United States	33401
42	Forest Investigative Site 125	West Palm Beach	Florida	United States	33407
43	Forest Investigative Site 075	Atlanta	Georgia	United States	30312
44	Forest Investigative Site 072	Atlanta	Georgia	United States	30338
45	Forest Investigative Site 042	Augusta	Georgia	United States	30904
46	Forest Investigative Site 094	Honolulu	Hawaii	United States	96814
47	Forest Investigative Site 95	Meridian	Idaho	United States	83646
48	Forest Investigative Site 082	Chicago	Illinois	United States	60607
49	Forest Investigative Site 096	Wichita	Kansas	United States	67203
50	Forest Investigative Site 065	Madisonville	Kentucky	United States	42431
51	Forest Investigative Site 123	Lafayette	Louisiana	United States	70503
52	Forest Investigative Site 106	Auburn	Maine	United States	04210
53	Forest Investigative Site 006	Oxon Hill	Maryland	United States	20745
54	Forest Investigative Site 067	Brockton	Massachusetts	United States	02301
55	Forest Investigative Site 110	Brockton	Massachusetts	United States	02301
56	Forest Investigative Site 018	Paw Paw	Michigan	United States	49079
57	Forest Investigative Site 021	Saint Clair Shores	Michigan	United States	48081
58	Forest Investigative Site 080	Columbia	Missouri	United States	65212
59	Forest Investigative Site 146	Elizabeth	New Jersey	United States	07202
60	Forest Investigative Site 071	Brooklyn	New York	United States	11203
61	Forest Investigative Site 081	New York	New York	United States	10001
62	Forest Investigative Site 035	Charlotte	North Carolina	United States	28209
63	Forest Investigative Site 051	Charlotte	North Carolina	United States	28262
64	Forest Investigative Site 077	Durham	North Carolina	United States	27704
65	Forest Investigative Site 100	Lenoir	North Carolina	United States	28645
66	Forest Investigative Site 041	Morehead City	North Carolina	United States	28557
67	Forest Investigative Site 050	Salisbury	North Carolina	United States	28144
68	Forest Investigative Site 091	Centerville	Ohio	United States	45459
69	Forest Investigative Site 089	Cincinnati	Ohio	United States	45242
70	Forest Investigative Site 122	Perrysburg	Ohio	United States	43551
71	Forest Investigative Site 087	Eugene	Oregon	United States	97404
72	Forest Investigative Site 088	Portland	Oregon	United States	97210
73	Forest Investigative Site 114	Harleysville	Pennsylvania	United States	19438
74	Forest Investigative Site 083	Pawtucket	Rhode Island	United States	02860
75	Forest Investigative Site 098	Columbia	South Carolina	United States	29201
76	Forest Investigative Site 115	Greer	South Carolina	United States	29651
77	Forest Investigative Site 105	Simpsonville	South Carolina	United States	29201
78	Forest Investigative Site 092	Sioux Falls	South Dakota	United States	57104
79	Forest Investigative Site 003	Carrollton	Texas	United States	75006-5810
80	Forest Investigative Site 116	Houston	Texas	United States	77074
81	Forest Investigative Site 120	Odessa	Texas	United States	79761
82	Forest Investigative Site 012	San Antonio	Texas	United States	78229
83	Forest Investigative Site 048	Sugar Land	Texas	United States	77479
84	Forest Investigative Site 040	Bountiful	Utah	United States	84010-5174
85	Forest Investigative Site 062	Salt Lake City	Utah	United States	84102
86	Forest Investigative Site 093	Salt Lake City	Utah	United States	84102
87	Forest Investigative Site 130	West Jordan	Utah	United States	84088
88	Forest Investigative Site 126	Arlington	Virginia	United States	22204

Sponsors and Collaborators

• Forest Laboratories

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT00673790
• Other Study ID Numbers: NEB-MD-04
• First Posted: May 7, 2008
• Last Update Posted: Feb 26, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Forest Laboratories: nebivolol; BYSTOLIC ™; hydrochlorothiazide; lisinopril; Prinivil (TM); Zestril (TM); losartan; Cozaar (TM); Impaired Fasting Glucose; Impaired Glucose Tolerance; hypertension
• Additional relevant MeSH terms: Hypertension; Glucose Intolerance; Losartan; Lisinopril; Nebivolol

Study Results

Participant Flow

Recruitment Details	May 2008 to March 2010 at 96 US sites, 72 sites randomized patients.
Pre-assignment Detail	A losartan or lisinopril run-in phase was required for all patients before assignment to Placebo or Nebivolol or Hydrochlorothiazide arms.

Arm/Group Title	Nebivolol	Hydrochlorothiazide (HCTZ)	Placebo
Arm/Group Description	Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration	Encapsulated Hydrochlorothiazide 12.5 mg or 25 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.	Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
Period Title: Overall Study
STARTED	223	212	102
COMPLETED	178	174	90
NOT COMPLETED	45	38	12

Baseline Characteristics

Arm/Group Title	Nebivolol	Hydrochlorothiazide (HCTZ)	Placebo	Total
Arm/Group Description	Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration	Encapsulated Hydrochlorothiazide 12.5 mg or 25 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.	Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.	Total of all reporting groups
Overall Participants	223	212	102	537
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.4 (9.6)	55.7 (10.4)	55.2 (11.3)	55.1 (10.3)
Age, Customized (Count of Participants)
Patients 18 to 65 years of age	190 85.2%	172 81.1%	81 79.4%	443 82.5%
Patients greater than or equal to 65 years of age.	33 14.8%	40 18.9%	21 20.6%	94 17.5%
Sex: Female, Male (Count of Participants)
Female	101 45.3%	97 45.8%	38 37.3%	236 43.9%
Male	122 54.7%	115 54.2%	64 62.7%	301 56.1%
Region of Enrollment (Count of Participants)
United States	223 100%	212 100%	102 100%	537 100%

Outcome Measures

1. Primary Outcome

Title	Trough Seated Diastolic Blood Pressure
Description	Change from Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12, Last Observation Carried Forward (LOCF).
Time Frame	Change from Baseline Visit 4 (Week 0) To Visit 8 (Week 12)

Outcome Measure Data

Analysis Population Description

The between-treatment-group comparison was performed by means of an analysis-of-covariance model with treatment group and study center as factors and baseline value as a covariate based on Intent-to-Treat (ITT) population. As pre-specified in the protocol, the change in seated DBP was performed between the nebivolol and placebo group.

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration	Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
Measure Participants	217	100
Mean (Standard Deviation) [mm Hg]	-9.4 (8.9)	-5.0 (9.5)

2. Secondary Outcome

Title	Plasma Glucose Level After an Oral Glucose Tolerance Test
Description	Change from Baseline in Plasma Glucose 2 Hours Post-oral Glucose 75 grams, given as part of an Oral Glucose Tolerance Test (OGTT). Last Observation Carried Forward.
Time Frame	Change from Baseline Visit 3 or 4 (Week -2 or 0) To Visit 8 (Week 12)

Outcome Measure Data

Analysis Population Description

The between-treatment-group comparison was performed by means of an analysis-of-covariance model with treatment group and study center as factors and baseline value as a covariate based on Intent-to-Treat (ITT) population.

Arm/Group Title	Nebivolol	Hydrochlorothiazide (HCTZ)	Placebo
Arm/Group Description	Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration	Encapsulated Hydrochlorothiazide 12.5 mg or 25 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.	Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
Measure Participants	217	209	100
Least Squares Mean (Standard Error) [g/mL]	0.20 (0.190)	0.31 (0.184)	-0.21 (0.247)

Adverse Events

Arm/Group Title	Nebivolol		Hydrochlorothiazide (HCTZ)		Placebo
Arm/Group Description	Encapsulated Nebivolol 5 mg, 10 mg, 20, mg, 40 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration		Encapsulated Hydrochlorothiazide 12.5 mg or 25 mg total daily dosage, oral administration with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.		Placebo with concomitant treatment consisting of lisinopril 10 mg total daily dosage, oral administration or losartan 50 mg total daily dosage, oral administration.
All Cause Mortality
	Nebivolol		Hydrochlorothiazide (HCTZ)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Nebivolol		Hydrochlorothiazide (HCTZ)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/223 (2.2%)		6/212 (2.8%)		2/102 (2%)
Cardiac disorders
Cardiac failure congestive	1/223 (0.4%)		0/212 (0%)		0/102 (0%)
Cardiac arrest	0/223 (0%)		1/212 (0.5%)		0/102 (0%)
Myocardial infaction	0/223 (0%)		2/212 (0.9%)		0/102 (0%)
Gastrointestinal disorders
Oesophageal stenosis	0/223 (0%)		1/212 (0.5%)		0/102 (0%)
Oesophagitis	0/223 (0%)		1/212 (0.5%)		0/102 (0%)
General disorders
Non-cardiac chest pain	1/223 (0.4%)		0/212 (0%)		0/102 (0%)
Chest pain	0/223 (0%)		1/212 (0.5%)		0/102 (0%)
Infections and infestations
Pneumonia	1/223 (0.4%)		0/212 (0%)		0/102 (0%)
Injury, poisoning and procedural complications
Fall	0/223 (0%)		0/212 (0%)		1/102 (1%)
Humerus fracture	0/223 (0%)		0/212 (0%)		1/102 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm	1/223 (0.4%)		0/212 (0%)		0/102 (0%)
Nervous system disorders
Basal ganglia haemorrage	1/223 (0.4%)		0/212 (0%)		0/102 (0%)
Migraine	0/223 (0%)		0/212 (0%)		1/102 (1%)
Psychiatric disorders
Depression	0/223 (0%)		1/212 (0.5%)		0/102 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/223 (0%)		1/212 (0.5%)		0/102 (0%)
Other (Not Including Serious) Adverse Events
	Nebivolol		Hydrochlorothiazide (HCTZ)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/223 (15.7%)		21/212 (9.9%)		14/102 (13.7%)
Cardiac disorders
Bradycardia	12/223 (5.4%)		0/212 (0%)		0/102 (0%)
Infections and infestations
Upper respiratory tract infection	12/223 (5.4%)		10/212 (4.7%)		7/102 (6.9%)
Nervous system disorders
Headache	12/223 (5.4%)		12/212 (5.7%)		7/102 (6.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.