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

NCT05279807 | Completed Phase 4 Results

• 1 other identifier: MEIN/20/ZoAm-Hyp/001
• Study Type: interventional
• Target: 277
• Locations: 1 country
• Sites: 1

Brief Summary

Study to assess the anti-hypertensive efficacy and safety of the extemporaneous combination of Zofenopril 30 mg in combination with Amlodipine 5 mg or AML 10 mg in lowering the sitting diastolic BP after 8 weeks of treatment in patients with uncontrolled BP previously treated with Zofenopril or Amlodipine (5 mg) monotherapies for at least 4 weeks.

Conditions

Hypertension

Keywords

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

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 Zofenopril (ZOF) 30 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 Zofenopril 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)

Zofenopril 30 mg

ACTIVE COMPARATOR

Single dose Phase (4 weeks): patients will be treated with Zofenopril 30 mg. Combination Phase (8 weeks) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy.

Drug: Zofenopril; Drug: Amlodipine

Amlodipine 5/10 mg

ACTIVE COMPARATOR

Single dose Phase (4 weeks): patients will be treated with Amlodipine 5 mg. Combination Phase (8 weeks) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy.

Drug: Zofenopril; Drug: Amlodipine

Interventions

Zofenopril DRUG

Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator.

Amlodipine 5/10 mg; Zofenopril 30 mg

Amlodipine DRUG

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

Amlodipine 5/10 mg; Zofenopril 30 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 Grade 1-2 hypertensive patients: with mean sitting SBP ≥140 mmHg and ≤179 mmHg and/or mean sitting DBP ≥ 90 mmHg and ≤109 mmHg at Screening, with ≥18 and ≤65 years of age, on monotherapy either with ZOF 30 mg or AML 5mg or any other ACE-I or CCBs (Felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, and nisoldipine) for at least 1 month before Visit 1 (Screening).
• Patients who are able to understand and give written informed consent at Screening
• Patients who are available for the entire trial period and willing to adhere to the protocol requirements
• 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 must refrain from donating or storing eggs. For females of reproductive potential: use of highly effective contraception (e.g., 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) such as:
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner (performed at least 2 months before screening) (if 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:

• Known contraindications, presence of not recommended/contraindicated concomitant therapy allergies, or significant history of hypersensitivity to zofenopril, amlodipine, other ACE-inhibitors or dihydropyridines, or any related products including excipients of the formulations as outlined in the Investigator's Brochure (IB), or summary of product characteristics (SmPCs) or local package inserts for AML 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, haematological, 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, valve replacement (transcatheter aortic valve implantation, mitral-clip),cerebrovascular accident (stroke, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischemic attack. Patients with who have undergone other surgery that in the in the opinion of the Investigator may limit the ability to evaluate the efficacy or safety of the tested medications.
• Patients with secondary hypertension of any aetiology such as renal diseases, pheochromocytoma, Cushing's syndrome hyperaldosteronism, renovascular disease, thyroid disorders
• 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)
• Patients with history of angioneurotic oedema
• 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)
• Participation in any other interventional drug trial or exposure to other investigational agents within 30 days before Screening (Visit 1)
• Inability to cooperate or any condition that, in the opinion of the Investigator, could increase the patient's risk of participating in the study or confound the outcome of the study
• Patients with conditions that, in the opinion of the Investigator, would prevent a careful adherence to the protocol
• Patients with severe hypotension
• Patients who suffer from shock (including cardiogenic shock)

Sponsors & Collaborators

• Menarini International Operations Luxembourg SA: lead

Study Sites (1)

Investigational site

Debrecen, 4025, Hungary

Location

MeSH Terms

Conditions

Hypertension

Interventions

zofenopril; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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

Model Details: Patients with uncontrolled BP on treatment with any Ace-i or any CCB, if eligible, will enter a 4-week run-in period. Patients will then be all assigned to mono-therapy with ZOF 30mg or AML 5mg for 4 weeks if in treatment with Ace-i or CCB respectively. At Visit 2 patients with uncontrolled BP, tolerating treatment and with adherence within 80%/120% ranges, will receive extemporaneous combination ZOF 30mg+AML 5mg, while patients with controlled BP, tolerating treatment or with adherence out of 80%/120% range, will be withdrawn from the study together with patients with SBP/DBP ≥ 180/100 mmHg. At Visit 3 (Visit 2 + 4 weeks ± 2 days) controlled patients will continue extemporaneous combination for additional 4 weeks ± 2 days, while uncontrolled patients will be up-titrated to ZOF 30mg/AML 10mg for the same time. Patients with SBP/DBP ≥ 180/100 mmHg or not tolerating extemporaneous combination or with adherence out of 80%/120% range, will be withdrawn from the study.

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: March 15, 2022
• Study Start: October 15, 2021
• Primary Completion: April 28, 2022
• Study Completion: April 28, 2022
• Last Updated: October 21, 2024
• Results First Posted: October 21, 2024

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)