Study to Evaluate Symptoms in Patients Treated With Nebivolol or Metoprolol Extended-release (ER) for Hypertension

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00547300
• Collaborator: Mylan Laboratories (Industry)
• Enrollment: 49
• Locations: 24
• Arms: 2
• Actual Duration (Months): 2.1
• Patients Per Site: 2
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study was to compare the tolerability of nebivolol to metoprolol ER in a general population of patients with mild to moderate hypertension receiving hydrochlorothiazide (HCTZ)

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Metoprolol ER; Drug: Nebivolol	Phase 3

Detailed Description

This study was an 18-week study to evaluate the tolerability of nebivolol compared to metoprolol ER in outpatients with mild to moderate hypertension taking HCTZ. It is a multi-center, randomized, double blind (DB), active-control, parallel-group study, starting with a 4-week HCTZ run-in phase, followed by a 12-week DB treatment phase. Patients meeting the entry criteria at the end of run-in are randomized to one of two treatment groups, nebivolol or metoprolol ER. Up-titration of dose of study drug will occur if needed during the first 4 weeks of the DB phase, after which there is an 8-week stable-dose period of treatment. A 2-week double-blind withdrawal phase follows, during which tapering off study drug occurs.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Tolerability of Nebivolol Compared With Metoprolol ER in Patients With Mild to Moderate Hypertension Taking Hydrochlorothiazide (HCTZ)
• Actual Study Start Date: Oct 31, 2007
• Actual Primary Completion Date: Jan 2, 2008
• Actual Study Completion Date: Jan 2, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nebivolol Nebivolol 5 mg, 10 mg or 20 mg	Drug: Nebivolol; Nebivolol once daily, oral administration
Active Comparator: Metoprolol ER Metoprolol ER 50 mg, 100 mg or 200 mg	Drug: Metoprolol ER; Metoprolol ER once daily, oral administration

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Patient Symptoms Questionnaire (PSQ) Derived Score [Measurements occured over a 14 week period, from Visit 2 (Week -2) to Visit 10 (Week 12)]

   The PSQ contained 44 possible symptoms rated from 0 (no discomfort) to 5 (extreme discomfort).

Secondary Outcome Measures

1. Peripheral Blood Pressure (BP) [Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14)]

2. Pulse Rate [Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14)]

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

• History of hypertension being treated with two medications, one of which must be HCTZ and the other of which must not be a beta-blocker or clonidine

• SBP of 135-155 mm Hg and/or DBP of >85 mm Hg at screening (Visit 1)

• SBP of 140-165 mm Hg and DBP > 90 mmHg at randomization (Visit 3)

Exclusion Criteria:

• Treatment with a beta-blocker or clonidine within 6 months of screening (Visit 1)

• Clinically significant respiratory disease (e.g., bronchial asthma, reactive airways disease, chronic obstructive pulmonary disease)

• Coronary artery disease requiring treatment with a calcium channel blocker or nitrates

• Clinically significant cardiovascular disease (e.g., myocardial infarction, cerebrovascular event, significant arrhythmia) within 6 months of screening (Visit 1)

• History of severe mental illness (including Major Depressive Disorder, psychosis, dementia, bipolar disorder) within 6 months of screening (Visit 1)

• Use of antipsychotic medication (e.g., dopamine receptor antagonists, serotonin dopamine receptor antagonists) or antidepressants

• Diabetes mellitus, type I or II

• Participation in a previous investigational study of nebivolol at any time

• Receipt of treatment with an investigational study drug within 30 days of screening (Visit 1)

• History of hypersensitivity to nebivolol, metoprolol ER, other beta-blockers, HCTZ, or other sulfonamide-derived drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Research Institute 014	Birmingham	Alabama	United States	35205
2	Forest Research Institute 028	Beverly Hills	California	United States	90211
3	Forest Research Institute 054	Encinitas	California	United States	92024
4	Forest Research Institute 025	Roseville	California	United States	95661
5	Forest Research Institute 013	Tustin	California	United States	92780
6	Forest Research Institute 053	Vista	California	United States	92083
7	Forest Research Institute 052	Walnut Creek	California	United States	94598
8	Forest Research Institute 033	Westlake Village	California	United States	91361
9	Forest Research Institute 010	DeLand	Florida	United States	32720
10	Forest Research Institute 019	Holly Hill	Florida	United States	32117
11	Forest Research Institute 036	Hollywood	Florida	United States	33023
12	Forest Research Institute 007	Pembroke Pines	Florida	United States	33024
13	Forest Research Institute 009	Atlanta	Georgia	United States	30338
14	Forest Research Institute 006	Oxon Hill	Maryland	United States	20745
15	Forest Research Institute 027	Las Vegas	Nevada	United States	89106
16	Forest Research Institute 050	Salisbury	North Carolina	United States	28144
17	Forest Research Institute 039	Wilmington	North Carolina	United States	28401
18	Forest Investigative Site 002	Charleston	South Carolina	United States	29407
19	Forest Research Institute 032	Greenville	South Carolina	United States	29615
20	Forest Research Institute 008	Nashville	Tennessee	United States	37203
21	Forest Research Institute 003	Carrollton	Texas	United States	75006
22	Forest Research Institute 012	San Antonio	Texas	United States	78229
23	Forest Research Institute 048	Sugar Land	Texas	United States	77479
24	Forest Research Institute 040	Bountiful	Utah	United States	84010

Sponsors and Collaborators

• Forest Laboratories
• Mylan Laboratories

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT00547300
• Other Study ID Numbers: NEB-MD-03
• First Posted: Oct 22, 2007
• Last Update Posted: May 21, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Forest Laboratories: Hypertension; Nebivolol; Beta blocker; Tolerability
• Additional relevant MeSH terms: Hypertension; Metoprolol; Nebivolol

Study Results

Participant Flow

Recruitment Details	Patient recruitment occurred over a four month period from October 2007 to January 2008 at 39 US sites.
Pre-assignment Detail	All patients went through a 4 week hydrochlorothiazide (HCTZ) run-in phase before randomization.

Arm/Group Title	Nebivolol	Metoprolol Extended-Release (ER)
Arm/Group Description	Nebivolol 5 mg, 10 mg or 20 mg	Metoprolol ER 50 mg, 100 mg or 200 mg
Period Title: Overall Study
STARTED	25	26
COMPLETED	0	0
NOT COMPLETED	25	26

Baseline Characteristics

Arm/Group Title	Nebivolol	Metoprolol Extended-Release (ER)	Total
Arm/Group Description	Nebivolol 5 mg, 10 mg or 20 mg	Metoprolol ER 50 mg, 100 mg or 200 mg	Total of all reporting groups
Overall Participants	25	24	49
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	22 88%	19 79.2%	41 83.7%
>=65 years	3 12%	5 20.8%	8 16.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.0 (8.67)	57.0 (9.32)	56.0 (8.95)
Sex: Female, Male (Count of Participants)
Female	13 52%	11 45.8%	24 49%
Male	12 48%	13 54.2%	25 51%
Region of Enrollment (Count of Participants)
United States	25 100%	24 100%	49 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Patient Symptoms Questionnaire (PSQ) Derived Score
Description	The PSQ contained 44 possible symptoms rated from 0 (no discomfort) to 5 (extreme discomfort).
Time Frame	Measurements occured over a 14 week period, from Visit 2 (Week -2) to Visit 10 (Week 12)

Outcome Measure Data

Analysis Population Description

Formal analysis of the primary endpoint was not conducted in this abbreviated study as the study was terminated before visit 10 was reached.

Arm/Group Title	Nebivolol	Metoprolol Extended-Release (ER)
Arm/Group Description	Nebivolol 5 mg, 10 mg or 20 mg	Metoprolol ER 50 mg, 100 mg or 200 mg
Measure Participants	0	0

2. Secondary Outcome

Title	Peripheral Blood Pressure (BP)
Time Frame	Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14)

Outcome Measure Data

Analysis Population Description

Formal analysis of the secondary endpoint was not conducted in this abbreviated study as the study was terminated before all visits were completed. No patients completed the study.

Arm/Group Title	Nebivolol	Metoprolol Extended-Release (ER)
Arm/Group Description	Nebivolol 5 mg, 10 mg or 20 mg	Metoprolol ER 50 mg, 100 mg or 200 mg
Measure Participants	0	0

3. Secondary Outcome

Title	Pulse Rate
Time Frame	Measurements occured over a 18 week period, from Visit 1 (Week -4) through Visit 11 (Week 14)

Outcome Measure Data

Analysis Population Description

Formal analysis of the secondary endpoint was not conducted in this abbreviated study as the study was terminated before all visits were completed. No patients completed the study.

Arm/Group Title	Nebivolol	Metoprolol Extended-Release (ER)
Arm/Group Description	Nebivolol 5 mg, 10 mg or 20 mg	Metoprolol ER 50 mg, 100 mg or 200 mg
Measure Participants	0	0

Adverse Events

Time Frame	Adverse Event data was collected over a four month period from October 2007 to January 2008.
Adverse Event Reporting Description	Non-serious adverse events based on the safety population of (n=49).
Arm/Group Title	Nebivolol		Metoprolol Extended-Release (ER)
Arm/Group Description	Nebivolol 5 mg, 10 mg or 20 mg		Metoprolol ER 50 mg, 100 mg or 200 mg
All Cause Mortality
	Nebivolol		Metoprolol Extended-Release (ER)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/26 (0%)
Serious Adverse Events
	Nebivolol		Metoprolol Extended-Release (ER)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Nebivolol		Metoprolol Extended-Release (ER)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/25 (20%)		3/24 (12.5%)
General disorders
Pain	2/25 (8%)		0/24 (0%)
Infections and infestations
Nasopharyngitis	2/25 (8%)		1/24 (4.2%)
Nervous system disorders
Headache	1/25 (4%)		2/24 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/25 (8%)		0/24 (0%)
Rhinorrhoea	2/25 (8%)		0/24 (0%)

Limitations/Caveats

Study was terminated early due to administrative reasons. Formal analyses of primary and secondary endpoints were not conducted in this study.

More Information

Certain Agreements

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

Sponsor can review results communications prior to public release & can embargo communications re: results for 60 days from time submitted to sponsor for review. PI shall not disclose sponsor's confidential information. Upon sponsor's request, PI shall delete any proprietary info & shall not include raw data in the publication. On sponsor's request, PI shall delay submission for any pub while sponsor files patent applications. Any publication will give recognition to Sponsor's support.