Study on the effectiveness and safety of combined treatment with nebivolol and amlodipine in mild to moderate hypertensive patients.

Open-label, multicenter, multinational, interventional clinical trial to assess efficacy and safety of the extemporaneous combination of nebivolol and amlodipine in grade 1-2 hypertensive patients versus each monotherapy - BOTTICELLI

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-005077-10-BG

Enrollment

302

Registered

2022-03-16

Start date

2022-04-28

Completion date

Unknown

Last updated

2023-09-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Grade 1-2 hypertension MedDRA version: 20.0 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 - Vascular disorders

Interventions

Trade Name: LOBIVON 5 mg tablets Product Name: Nebivolol Pharmaceutical Form: Tablet INN or Proposed INN: NEBIVOLOL CAS Number: 99200-09-6 Concentration unit: mg milligram(s) Concentration type: equal

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. 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 ESC/ESH guidelines definition), =18 and =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. 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 characteristics (SmPC) or local package inserts for NEB and AML. 2. 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. 3. 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. 4. Patients with condition of hypotension with SBP <90 mmHg and/or DBP <60mmHg. 5. Acute heart failure, cardiogenic shock or episodes of heart failure decompensation requiring intravenous inotropic therapy. 6. Patients with secondary hypertension of any etiology including renal diseases, pheochromocytoma, Cushing’s syndrome, hyperaldosteronism, renovascular disease, thyroid disorders. 7. 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. 8. Patients with severe renal impairment or renal transplant. 9. Patients with clinically relevant hepatic impairment. 10. Patients with sick sinus syndrome, including sino-atrial block. 11. Patients with second- or third-degree heart block (without a pacemaker). 12. Patients with history of bronchospasm and bronchial asthma. 13. Patients with untreated pheochromocytoma. 14. Patients with bradycardia (heart rate <60 bpm; <50 bpm in patients already on BBs treatment). 15. Patient with metabolic acidosis. 16. Patients with severe peripheral circulatory disturbances. 17. Participation in another interventional study within the last 4 weeks before screening (Visit 1). 18. Patients with diseases that, in the opinion of the Investigator, prevent a careful adherence to the protocol. 19. Patients using and not suitable for withdrawing the prohibited medications prior to the administration of study treatment.

Design outcomes

Primary

Measure	Time frame
Main Objective: To assess the antihypertensive efficacy of the extemporaneous combination of nebivolol (NEB) 5 mg with amlodipine (AML) 5 mg or AML 10 mg in lowering the sitting diastolic blood pressure (DBP) between Visit 2 (Week 0) and Visit 4 (Week 8) in patients with uncontrolled BP, previously treated with NEB 5 mg or AML 5 mg monotherapies for at least 4 weeks.;Secondary Objective: 1.To assess the antihypertensive efficacy of the extemporaneous combination of NEB 5mg with AML 5mg or AML 10mg in lowering SBP between Visit 2 and 4 in patients with uncontrolled BP previously treated with NEB 5mg or AML 5mg monotherapies for at least 4 weeks. 2.To assess the antihypertensive efficacy of the extemporaneous combination of NEB/AML 5/10mg versus extemporaneous combination NEB/AML 5/5mg, in lowering sitting DBP and SBP between Visit 3 and 4 in patients with uncontrolled BP previously treated with NEB 5mg or AML 5mg monotherapies for at least 4 weeks. 3.To assess the antihypertensive efficacy of the extemporaneous combination of NEB 5mg with AML 5mg or AML 10mg by evaluating the patients who achieve BP goal at Visit 2, 3, and 4. 4.To assess the compliance to the treatment at Visit 2, 3, and 4. 5.To evaluate the safety and tolerability of the monotherapies (NEB 5mg and AML 5mg) and of the extemporaneous combinations (NEB 5mg and AML 5/10mg) after 8 weeks of treatment.;Primary end point(s): Change in mean sitting DBP between Visit 2 (Week 0) and Visit 4 (Week 8).;Timepoint(s) of evaluation of this end point: Visit 2 (Week 0) and Visit 4 (Week 8)	—

Measure

Time frame

Main Objective: To assess the antihypertensive efficacy of the extemporaneous combination of nebivolol (NEB) 5 mg with amlodipine (AML) 5 mg or AML 10 mg in lowering the sitting diastolic blood pressure (DBP) between Visit 2 (Week 0) and Visit 4 (Week 8) in patients with uncontrolled BP, previously treated with NEB 5 mg or AML 5 mg monotherapies for at least 4 weeks.;Secondary Objective: 1.To assess the antihypertensive efficacy of the extemporaneous combination of NEB 5mg with AML 5mg or AML 10mg in lowering SBP between Visit 2 and 4 in patients with uncontrolled BP previously treated with NEB 5mg or AML 5mg monotherapies for at least 4 weeks. 2.To assess the antihypertensive efficacy of the extemporaneous combination of NEB/AML 5/10mg versus extemporaneous combination NEB/AML 5/5mg, in lowering sitting DBP and SBP between Visit 3 and 4 in patients with uncontrolled BP previously treated with NEB 5mg or AML 5mg monotherapies for at least 4 weeks. 3.To assess the antihypertensive efficacy of the extemporaneous combination of NEB 5mg with AML 5mg or AML 10mg by evaluating the patients who achieve BP goal at Visit 2, 3, and 4. 4.To assess the compliance to the treatment at Visit 2, 3, and 4. 5.To evaluate the safety and tolerability of the monotherapies (NEB 5mg and AML 5mg) and of the extemporaneous combinations (NEB 5mg and AML 5/10mg) after 8 weeks of treatment.;Primary end point(s): Change in mean sitting DBP between Visit 2 (Week 0) and Visit 4 (Week 8).;Timepoint(s) of evaluation of this end point: Visit 2 (Week 0) and Visit 4 (Week 8)

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Secondary

Measure	Time frame
Secondary end point(s): 1. Change in mean sitting SBP between Visit 2 (Week 0) and Visit 4 (Week 8). 2. Change in mean sitting DBP and SBP between Visit 3 (Week 4) and 4 (Week 8) in patients receiving extemporaneous combination of NEB/AML 5/5 mg versus patients uptitrated to the extemporaneous combination of NEB/AML 5/10 mg. 3. Number and proportion of patients achieving the BP goal (sitting SBP/DBP <130/80 mmHg) at Visit 2 (Week 0), Visit 3 (Week 4) and Visit 4 (Week 8). 4. Adherence to the treatments (% of doses taken/doses to be taken) at Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8). 5. Safety and tolerability of the monotherapies (NEB 5 mg and AML 5 mg) and of the extemporaneous combinations (NEB 5 mg and AML 5mg or AML 10 mg) will be measured by incidence, intensity (severity), seriousness of Adverse Events (AEs) during the study period, (screening, run-in period and assessment period), relationship to the study treatments, clinically significant abnormal change in vital signs, electrocardiogram (ECG) (only at Visit 1 and Visit 4), laboratory parameters (if applicable) at Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8).;Timepoint(s) of evaluation of this end point: 1. Visit 2 (Week 0) and Visit 4 (Week 8) 2. Visit 3 (Week 4) and 4 (Week 8) 3. Visit 2 (Week 0), Visit 3 (Week 4) and Visit 4 (Week 8) 4. Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8) 5. Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8)	—

Measure

Time frame

Secondary end point(s): 1. Change in mean sitting SBP between Visit 2 (Week 0) and Visit 4 (Week 8). 2. Change in mean sitting DBP and SBP between Visit 3 (Week 4) and 4 (Week 8) in patients receiving extemporaneous combination of NEB/AML 5/5 mg versus patients uptitrated to the extemporaneous combination of NEB/AML 5/10 mg. 3. Number and proportion of patients achieving the BP goal (sitting SBP/DBP <130/80 mmHg) at Visit 2 (Week 0), Visit 3 (Week 4) and Visit 4 (Week 8). 4. Adherence to the treatments (% of doses taken/doses to be taken) at Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8). 5. Safety and tolerability of the monotherapies (NEB 5 mg and AML 5 mg) and of the extemporaneous combinations (NEB 5 mg and AML 5mg or AML 10 mg) will be measured by incidence, intensity (severity), seriousness of Adverse Events (AEs) during the study period, (screening, run-in period and assessment period), relationship to the study treatments, clinically significant abnormal change in vital signs, electrocardiogram (ECG) (only at Visit 1 and Visit 4), laboratory parameters (if applicable) at Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8).;Timepoint(s) of evaluation of this end point: 1. Visit 2 (Week 0) and Visit 4 (Week 8) 2. Visit 3 (Week 4) and 4 (Week 8) 3. Visit 2 (Week 0), Visit 3 (Week 4) and Visit 4 (Week 8) 4. Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8) 5. Visit 2 (Week 0), Visit 3 (Week 4), and Visit 4 (Week 8)

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Countries

Bulgaria, Poland

Contacts

Public ContactClinical Operation Director

Menarini

pfabrizzi@menarini.it+39 055 5680459

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026