Effectiveness and Safety of Combination of Nebivolol and Amlodipine in Hypertensive Patients Versus Each Monotherapy

NCT05513937 | Completed Phase 4 Results

• 1 other identifier: MEIN/21/AmNe-Hyp/001
• Study Type: interventional
• Target: 301
• Locations: 1 country
• Sites: 1

Brief Summary

Study to assess the anti-hypertensive efficacy and safety of the extemporaneous combination of Nebivolol 5 mg in combination with Amlodipine 5 mg or AML 10 mg in lowering the sitting diastolic BP after 8 weeks of treatment inpatients with uncontrolled BP previously treated with Nebivolol (NEB) or Amlodipine (5 mg) monotherapies for at least 4 weeks.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in Mean Sitting Diastolic Blood Pressure (DBP) Between Visit 2 (Week 0) and Visit 4 (Week 8)

  To assess the antihypertensive efficacy of the extemporaneous combination of Nebivolol (NEB) 5 mg in combination with Amlodipine (AML) 5 mg or AML 10 mg in lowering the sitting diastolic BP between Visit 2 (Week 0) and Visit 4 (Week 8) in patients with uncontrolled BP previously treated with Nebivolol or Amlodipine (5 mg) monotherapies for at least 4 weeks during run-in period.

  From Visit 2 (week 0) to Visit 4 (week 8) for a total of 8 weeks

Study Arms (2)

Nebivolol 5 mg

ACTIVE COMPARATOR

MONOTHERAPY PHASE 4 weeks (Run-in from -4 week to week 0): patients will be treated with Nebivolol 5mg COMBINATION THERAPY PHASE 8 weeks (from week 0 to week 8): uncontrolled patients during Monotherapy Phase will be treated with the extemporaneous combination of Nebivolol 5mg and Amlodipine 5mg for 4 weeks (from week 0 to week 4). Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks (from week 4 to week 8) while controlled patients with Nebivolol 5mg/Amlodipine 5mg will continue with the same therapy.

Drug: Nebivolol; Drug: Amlodipine

Amlodipine 5/10 mg

ACTIVE COMPARATOR

MONOTHERAPY PHASE 4 weeks (Run-in from -4 week to week 0): patients will be treated with Amlodipine 5mg COMBINATION THERAPY PHASE 8 weeks (from week 0 to week 8): uncontrolled patients during Monotherapy Phase will be treated with the extemporaneous combination of Nebivolol 5mg and Amlodipine 5mg for 4 weeks (from week 0 to week 4). Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks (from week 4 to week 8) while controlled patients with Nebivolol 5mg/Amlodipine 5mg will continue with the same therapy.

Drug: Nebivolol; Drug: Amlodipine

Interventions

Nebivolol DRUG

Tablets administered orally once daily according instructions provided by Principal Investigator.

Amlodipine 5/10 mg; Nebivolol 5 mg

Amlodipine DRUG

Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.

Amlodipine 5/10 mg; Nebivolol 5 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with Grade 1 - 2 hypertension with mean sitting SBP ≥140 mmHg and ≤179 mmHg and/or mean sitting DBP ≥90 mmHg and ≤109 mmHg at screening (in accordance with the 2018 European Society of Cardiology / European Society of Hypertension guidelines definition), ≥18 and \<65 years of age, on monotherapy treatment either with BBs or CCBs for at least 4 weeks before Visit 1 (screening).
• Patients are able to understand and have freely given written informed consent at Screening Visit.
• Patients who are able to comply with all study procedures and who are available for the duration of the study.
• Ability to take oral medication and willing to adhere to the drug regimen.
• Female patients are eligible to participate if not pregnant, or not breastfeeding and if they refrain from donating or storing eggs. For females of reproductive potential: use of highly effective contraception (eg. method of birth control throughout the study period and for 4 weeks after study completion defined as a method which results in a failure rate of \<1% per year) such as:
• Combined hormonal contraception (estrogen- and progestogen-containing) associated with inhibition of ovulation (oral, intravaginal, and transdermal).
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, and implantable).
• Intrauterine device.
• Intrauterine hormone-releasing system.
• Bilateral tubal occlusion.
• Vasectomized partner (procedure conducted at least 2 months before the screening), (provided the partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success).
• A male patient must agree to use contraception during the whole study period and for at least 1 week after the last dose of study treatment and refrain from donating sperms during this period.

You may not qualify if:

• Patients with significant history of hypersensitivity to nebivolol, amlodipine, other BBs or other dihydropyridines, or any related products (including excipients of the formulations) as outlined in the relevant Investigators Brochures, summary of product characteristics12,13 or local package inserts for NEB and AML.
• Patients with serious disorders (in the opinion of the Investigator) which may limit the ability to evaluate the efficacy or safety of the tested medications, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, hematological, or oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic patients.
• Patients having a history of the following conditions within the last 6 months: myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, bypass surgery, heart failure, hypertensive encephalopathy, valve replacement (transcatheter aortic valve implantation, mitraclip), cerebrovascular accident (stroke), or transient ischemic attack.
• Patients with condition of hypotension with SBP \<90 mmHg and/or DBP \<60 mmHg.
• Acute heart failure, cardiogenic shock, or episodes of heart failure decompensation requiring intravenous inotropic therapy.
• Patients with secondary hypertension of any etiology including renal diseases, pheochromocytoma, Cushing's syndrome, hyperaldosteronism, renovascular disease, and thyroid disorders.
• Patients with a narrowing of the aortic or bicuspid valve, an obstruction of cardiac outflow (obstructive, hypertrophic cardiomyopathy), obstruction of the outflow tract of the left ventricle (eg. high grade aortic stenosis) or symptomatic coronary disease.
• Patients with severe renal impairment or renal transplant.
• Patients with clinically relevant hepatic impairment.
• Patients with sick sinus syndrome, including sino-atrial block.
• Patients with second- or third-degree heart block (without a pacemaker).
• Patients with history of bronchospasm and bronchial asthma.
• Patients with untreated pheochromocytoma.
• Patients with bradycardia (heart rate \<60 bpm; \<50 bpm in patients already on BBs treatment).
• Patient with metabolic acidosis.

Sponsors & Collaborators

• Menarini International Operations Luxembourg SA: lead

Study Sites (1)

Medical Center Hera EOOD

Sofia, 1510, Bulgaria

Location

MeSH Terms

Conditions

Hypertension

Interventions

Nebivolol; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dihydropyridines; Pyridines

Results Point of Contact

• Title: Clinical Operation Director
• Organization: A. Menarini Industrie Farmaceutiche Riunite SrL

pfabrizzi@menarini.it

055 5680459

Study Officials

• Massimo Volpe

  University "Sapienza" Rome

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 24, 2022
• Study Start: May 12, 2022
• Primary Completion: November 15, 2022
• Study Completion: November 15, 2022
• Last Updated: February 4, 2025
• Results First Posted: February 4, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)