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

Inclusion Criteria:

1. Male or female patients with Grade 1 - 2 hypertension with mean sitting SBP ≥140mmHg and ≤179 mmHg and/or mean sitting DBP ≥90 mmHg and ≤109 mmHg at screening (inaccordance with the 2018 European Society of Cardiology / European Society ofHypertension guidelines definition), ≥18 and <65 years of age, on monotherapytreatment either with BBs or CCBs for at least 4 weeks before Visit 1 (screening).

2. Patients are able to understand and have freely given written informed consent atScreening Visit.

3. Patients who are able to comply with all study procedures and who are available forthe duration of the study.

4. Ability to take oral medication and willing to adhere to the drug regimen.

5. Female patients are eligible to participate if not pregnant, or not breastfeedingand if they refrain from donating or storing eggs. For females of reproductivepotential: use of highly effective contraception (eg. method of birth controlthroughout the study period and for 4 weeks after study completion defined as amethod 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 thescreening), (provided the partner is the sole sexual partner of the trialparticipant and that the vasectomized partner has received medical assessmentof the surgical success).

6. A male patient must agree to use contraception during the whole study period and forat least 1 week after the last dose of study treatment and refrain from donatingsperms during this period.

Exclusion Criteria:

1. Patients with significant history of hypersensitivity to nebivolol, amlodipine,other BBs or other dihydropyridines, or any related products (including excipientsof the formulations) as outlined in the relevant Investigators Brochures, summary ofproduct characteristics12,13 or local package inserts for NEB and AML.

2. Patients with serious disorders (in the opinion of the Investigator) which may limitthe ability to evaluate the efficacy or safety of the tested medications, includingcerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal,endocrine or metabolic, hematological, or oncological, neurological, and psychiatricdiseases. 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 <60 mmHg.

5. Acute heart failure, cardiogenic shock, or episodes of heart failure decompensationrequiring intravenous inotropic therapy.

6. Patients with secondary hypertension of any etiology including renal diseases,pheochromocytoma, Cushing's syndrome, hyperaldosteronism, renovascular disease, andthyroid disorders.

7. Patients with a narrowing of the aortic or bicuspid valve, an obstruction of cardiacoutflow (obstructive, hypertrophic cardiomyopathy), obstruction of the outflow tractof the left ventricle (eg. high grade aortic stenosis) or symptomatic coronarydisease.

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 BBstreatment).

15. Patient with metabolic acidosis.

16. Patients with severe peripheral circulatory disturbances.

17. Participation in another interventional study within the last 4 weeks beforeScreening Visit (Visit 1).

18. Patients with diseases that, in the opinion of the Investigator, prevent a carefuladherence to the protocol.

19. Patients using and not suitable for withdrawing the prohibited medications prior tothe administration of study treatment.