Effectiveness and Safety of Combination of Nebivolol and Zofenopril in Hypertensive patIents Versus Each Monotherapy

NCT05257148 | Completed Phase 4 Results

• 2 other identifiers: MEIN/19/ZoNe-HYP/0012020-002340-23
• Study Type: interventional
• Target: 283
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label, interventional clinical trial to assess effectiveness and safety of the extemporaneous combination of nebivolol and zofenopril calcium in grade 1 to 2 hypertensive patients versus each monotherapy

Conditions

Hypertension

Keywords

Hypertension; Combination Therapy; Zofenopril; Nebivolol; Fixed Dose Combination

Outcome Measures

Primary Outcomes (1)

• Change in Mean Sitting DBP Between Week 0 (Visit 2) and Week 8 (Visit 3)

  To assess the antihypertensive efficacy of the extemporaneous combination of Nebivolol (NEB) 5 mg and Zofenopril (ZOF) 30 mg in lowering sitting diastolic blood pressure (DBP) from baseline (Visit 2) after 8 weeks of treatment (Visit 3), in patients with uncontrolled blood pressure (BP) who were previously treated with NEB or ZOF monotherapies for at least 4 weeks.

  From Baseline (Week 0 - Visit 2) to week 8 (Visit 3)

Study Arms (2)

Zofenopril arm

ACTIVE COMPARATOR

MONOTHERAPY PERIOD (one month): patients will be treated with Zofenopril 30 mg. COMBINATION THERAPY PERIOD (two months) patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Nebivolol 5mg

Drug: Zofenopril 30 mg; Drug: Zofenopril 30 mg + Nebivolol 5 mg

Nebivolol arm

ACTIVE COMPARATOR

MONOTHERAPY PERIOD (one month): patients will be treated with Nebivolol 5 mg. COMBINATION THERAPY PERIOD (two months) patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Nebivolol 5 mg

Drug: Nebivolol 5 mg; Drug: Zofenopril 30 mg + Nebivolol 5 mg

Interventions

Zofenopril 30 mg DRUG

Film-Coated tablets administered as one single dose to be taken in the morning (from 6 am to 10 am) with no restriction on food intake

Zofenopril arm

Nebivolol 5 mg DRUG

Tablet administered as one single dose to be taken in the morning (from 6 am to 10 am) with no restriction on food intake

Nebivolol arm

Zofenopril 30 mg + Nebivolol 5 mg DRUG

Both Film coated tablets of Zofenopril 30 mg and Nebivolol 5 mg Tablets will be taken in the morning (from 6 am to 10 am) with no restriction on food intake

Nebivolol arm; Zofenopril arm

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 Caucasian uncontrolled hypertensive patients (see definition in criterion 3) ≥18 and \<65 years of age, in monotherapy either with ACE-i or BBs since at least 1 month, at Screening (Visit 1)
• Patients are able to understand and have freely given written informed consent at Screening
• Patients with mean sitting Systolic Blood Pressure ≥140 mmHg and ≤179 mmHg and/or mean sitting Diastolic Blood Pressure ≥ 90 mmHg and ≤109 mmHg at Screening (Visit 1)
• Patient 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
• A female patient of childbearing potential is eligible to participate if she is not pregnant, or not breastfeeding. A woman is considered fertile following menarche and until becoming postmenopausal unless permanently sterile. Women of childbearing potential must agree to 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 less than 1% per year) and also must refrain from donating or storing eggs during this time. Highly effective contraception methods can be: a Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) b Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) c Intrauterine device (IUD) d Intrauterine hormone-releasing system (IUS) e Bilateral tubal occlusion f Vasectomized partner (provided that 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 with female partner 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:

• Known contraindications, allergies, or hypersensitivities to any of the study medications or excipient as outlined in the investigators brochures (IBs), summary of product characteristics (SmPCs) or local package inserts for NEB and ZOF
• 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 within the last 6 months:
• myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, bypass surgery, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischemic attack
• Patients with secondary hypertension of any etiology such as renal diseases, pheochromocytoma, or Cushing's syndrome
• Patients with severe heart failure (New York Heart Association classification III-IV), a narrowing of the aortic or bicuspid valve, an obstruction of cardiac outflow (obstructive, hypertrophic cardiomyopathy) or symptomatic coronary disease
• Patients with clinical evidence of renal disease as per the Investigator's judgement (including renovascular occlusive disease, nephrectomy and/or renal transplant, bilateral renal artery stenosis or unilateral renal artery stenosis in a solitary kidney, or severe renal impairment)
• History of angioneurotic edema
• 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)
• History of bronchospasm and bronchial asthma
• Patients with bradycardia (heart rate \<60 bpm)
• Patient with metabolic acidosis
• Patients with severe peripheral circulatory disturbances

Sponsors & Collaborators

• Menarini International Operations Luxembourg SA: lead

Study Sites (1)

Istituto Clinico Humanitas

Milan, 20089, Italy

Location

MeSH Terms

Conditions

Hypertension

Interventions

zofenopril; Nebivolol

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

Results Point of Contact

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

pfabrizzi@menarini.it

+39 055 5680459

Study Officials

• Massimo Volpe, Professor

  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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open Label, two period study. Patients eligible from screening will enter the run-in period on the same day. Patients previously receiving Zofenopril or any other ACE-inhibitor will enter into the run-in period with Zofenopril monotherapy while patients receiving Nebivolol or any other Beta Blockers will enter into the Run-in period with Nebivolol monotherapy in a 1:1 ratio. Only patients with uncontrolled BP (sitting Systolic Blood Pressure/Diastolic Blood Pressure\>130/80 mmHg) and whose adherence to the treatment ranges from 80% to 120%, will enter the assessment period to receive the extemporaneous combination of NEB and ZOF; while the patients with controlled sitting BP (Systolic Blood Pressure/Diastolic Blood Pressure ≤130/80 mmHg) and/or the patients who do not tolerate the treatment and patients with uncontrolled BP whose adherence to the therapy do not range from 80% to 120%, will be withdrawn from the study.

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: February 25, 2022
• Study Start: May 26, 2021
• Primary Completion: December 22, 2021
• Study Completion: December 22, 2021
• Last Updated: September 20, 2024
• Results First Posted: September 20, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)