Trial Outcomes & Findings for Evaluation of the Long-term Safety and Tolerability of Metoprolol Versus Nebivolol in Patients With Hypertension (NCT NCT00142584)

Last Updated: 2022-03-15

Results Overview

The primary efficacy parameter was the change in the average trough sitting DBP at the end of treatment (Visit 10 or Early Termination) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 \[NCT00145210\]).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

336 participants

Primary outcome timeframe

Through study duration (approximately 18 months)

Results posted on

2022-03-15

Participant Flow

Participant milestones

Participant milestones
Measure	1-NEB Nebivolol Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET Metoprolol Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Overall Study STARTED	252	84
Overall Study COMPLETED	108	28
Overall Study NOT COMPLETED	144	56

Reasons for withdrawal

Reasons for withdrawal
Measure	1-NEB Nebivolol Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET Metoprolol Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Overall Study Sponsor Termination of Study, etc.	72	16
Overall Study Withdrawal by Subject	30	16
Overall Study Lost to Follow-up	22	12
Overall Study Adverse Event	14	5
Overall Study Protocol Violation	4	7
Overall Study Treatment Failure	2	0

Baseline Characteristics

Evaluation of the Long-term Safety and Tolerability of Metoprolol Versus Nebivolol in Patients With Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1-NEB n=252 Participants Nebivolol Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET n=84 Participants Metoprolol Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.	Total n=336 Participants Total of all reporting groups
Age, Continuous	50.8 years STANDARD_DEVIATION 9.86 • n=5 Participants	50.1 years STANDARD_DEVIATION 9.76 • n=7 Participants	50.6 years STANDARD_DEVIATION 9.83 • n=5 Participants
Sex: Female, Male Female	130 Participants n=5 Participants	44 Participants n=7 Participants	174 Participants n=5 Participants
Sex: Female, Male Male	122 Participants n=5 Participants	40 Participants n=7 Participants	162 Participants n=5 Participants
Race/Ethnicity, Customized Black	252 Participants n=5 Participants	84 Participants n=7 Participants	336 Participants n=5 Participants
Region of Enrollment United States	252 participants n=5 Participants	84 participants n=7 Participants	336 participants n=5 Participants

PRIMARY outcome

Timeframe: Through study duration (approximately 18 months)

Outcome measures

Outcome measures
Measure	1-NEB n=252 Participants Nebivolol (NEB) Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET n=84 Participants Metoprolol (MET) Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline	-14.0 mm Hg Standard Deviation 9.80	-10.9 mm Hg Standard Deviation 8.73

SECONDARY outcome

Timeframe: Through study completion (approximately 18 months)

Population: The overall number of participants analyzed equals the number of randomized patients at study start; the numbers analyzed at each visit equal the number of patients at each treatment visit.

Data for the analysis of the change from baseline in mean trough sitting DBP at each study visit (Visits 1 through 9) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 \[NCT00145210\]) by treatment group are provided below.

Outcome measures

Outcome measures
Measure	1-NEB n=252 Participants Nebivolol (NEB) Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET n=84 Participants Metoprolol (MET) Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 1	-8.3 mm Hg Standard Deviation 8.24	-8.4 mm Hg Standard Deviation 9.15
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 6	-14.5 mm Hg Standard Deviation 8.49	-12.1 mm Hg Standard Deviation 7.94
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 7	-15.5 mm Hg Standard Deviation 8.55	-13.1 mm Hg Standard Deviation 8.74
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 8	-16.3 mm Hg Standard Deviation 8.59	-12.4 mm Hg Standard Deviation 6.78
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 2	-8.4 mm Hg Standard Deviation 8.39	-8.4 mm Hg Standard Deviation 7.89
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 3	-10.6 mm Hg Standard Deviation 8.51	-9.8 mm Hg Standard Deviation 8.07
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 4	-12.1 mm Hg Standard Deviation 8.55	-10.7 mm Hg Standard Deviation 8.20
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 5	-13.0 mm Hg Standard Deviation 8.03	-12.4 mm Hg Standard Deviation 7.41
Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline Visit 9	-16.7 mm Hg Standard Deviation 7.91	-13.7 mm Hg Standard Deviation 7.05

SECONDARY outcome

Timeframe: Through study completion (approximately 18 months)

Summary of Participants that experienced one or more TEAEs by Treatment Group-Safety Population

Outcome measures

Outcome measures
Measure	1-NEB n=252 Participants Nebivolol (NEB) Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET n=84 Participants Metoprolol (MET) Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	150 Participants	51 Participants

Adverse Events

1-NEB

Serious events: 11 serious events

Other events: 74 other events

Deaths: 3 deaths

2-MET

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	1-NEB n=252 participants at risk Nebivolol Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET n=84 participants at risk Metoprolol Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Nervous system disorders HEADACHE	6.7% 17/252 • Through study completion (approximately 18 months)	3.6% 3/84 • Through study completion (approximately 18 months)
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 14/252 • Through study completion (approximately 18 months)	4.8% 4/84 • Through study completion (approximately 18 months)
Infections and infestations Nasopharyngitis	4.8% 12/252 • Through study completion (approximately 18 months)	1.2% 1/84 • Through study completion (approximately 18 months)
Musculoskeletal and connective tissue disorders Back pain	4.0% 10/252 • Through study completion (approximately 18 months)	4.8% 4/84 • Through study completion (approximately 18 months)
Infections and infestations Upper respiratory tract infection	3.2% 8/252 • Through study completion (approximately 18 months)	4.8% 4/84 • Through study completion (approximately 18 months)
General disorders Peripheral edema	2.8% 7/252 • Through study completion (approximately 18 months)	4.8% 4/84 • Through study completion (approximately 18 months)
Infections and infestations Sinusitis	2.0% 5/252 • Through study completion (approximately 18 months)	4.8% 4/84 • Through study completion (approximately 18 months)
Respiratory, thoracic and mediastinal disorders Dyspnea	0.40% 1/252 • Through study completion (approximately 18 months)	4.8% 4/84 • Through study completion (approximately 18 months)

Additional Information

M. Rachel Kirker, PhD, Director, Clinical Oversight & Inspection Readiness

Viatris Inc

Phone: 724-485-6170

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator Study Agreement: Publication Clause - Details of the Study and its results shall not be publicized or published in any form without prior consent of Covance and the Sponsor, Mylan.
Publication restrictions are in place

Restriction type: OTHER

Measure	1-NEB n=252 participants at risk Nebivolol Nebivolol: Patients randomized to nebivolol will initiate therapy with nebivolol 5 mg once daily for 4 weeks.	2-MET n=84 participants at risk Metoprolol Metoprolol: Patients randomized to metoprolol will initiate therapy with 100 mg once daily for 4 weeks.
Blood and lymphatic system disorders IRON DEFICIENCY ANAEMIA	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
General disorders CHEST PAIN	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
General disorders NON-CARDIAC CHEST PAIN	0.00% 0/252 • Through study completion (approximately 18 months)	1.2% 1/84 • Number of events 1 • Through study completion (approximately 18 months)
General disorders PYREXIA	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Infections and infestations PNEUMONIA	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Injury, poisoning and procedural complications ANIMAL BITE	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Injury, poisoning and procedural complications ROAD TRAFFIC ACCIDENT	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Injury, poisoning and procedural complications WOUND	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Metabolism and nutrition disorders DIABETES MELLITUS	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Musculoskeletal and connective tissue disorders LUMBAR SPINAL STENOSIS	0.00% 0/252 • Through study completion (approximately 18 months)	1.2% 1/84 • Number of events 1 • Through study completion (approximately 18 months)
Musculoskeletal and connective tissue disorders SPINAL OSTEOARTHRITIS	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.79% 2/252 • Number of events 2 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Nervous system disorders CEREBRAL ARTERY OCCLUSION	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Nervous system disorders CERVICAL MYELOPATHY	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Nervous system disorders HEADACHE	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Psychiatric disorders ALCOHOLISM	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Psychiatric disorders CONVERSION DISORDER	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)
Reproductive system and breast disorders PROSTATITIS	0.40% 1/252 • Number of events 1 • Through study completion (approximately 18 months)	0.00% 0/84 • Through study completion (approximately 18 months)