Grade 1-2 hypertension MedDRA version: 20.0 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Trade Name: ZOPRANOL - 28 COMPRESSE RIVESTITE CON FILM 30 MG IN BLISTER (PVDC/PVC/AL)
Product Name: Zofenopril calcium
Product Code: [not applicable]
Pharmaceutical Form: Film-coated tablet
INN or Pr
Sponsors
MENARINI INTERNATIONAL OPERATIONS LUXEMBOURG SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be considered eligible for inclusion in the study only if all the following criteria are met: 1.Male or female Grade 1-2hypertensive 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, in monotherapy either with ZOF 30 mg or AML 5 mg, orany other ACE-I or CCBs (Felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, and nisoldipine) for at least 1 months before Visit 1 (Screening). 2.Patients who are able to understand and give written informed consent at Screening 3.Patients who are available for the entire trial period and willing to adhere to the protocol requirements 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 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 partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success) 6.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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Any patient who meets any of the following criteria will not qualify for entry into the study: 1.Known contraindications, presence of not recommended / contraindicated concomitant therapy allergies, or significant history of hypersensitivity to zofenopril, amlodipine, other ACE-inhibitors or dihydropyridines calcium channel blockers, 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 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, haematological, or oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic patients 3.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, MitraClip), 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. 4.Patients with secondary hypertension of any aetiology such as renal diseases, pheochromocytoma, Cushing’s syndrome hyperaldosteronism, renovascular disease, thyroid disorders 5.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 6.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) 7.Patients with history of angioneurotic oedema 8.Patients with clinically relevant hepatic impairment 9.Patients with sick sinus syndrome, including sino-atrial block 10.Patients with second- or third-degree heart block (without a pacemaker) 11.Participation in any other interventional drug trial or exposure to other investigational agents within 30 days before Screening (Visit 1) 12.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 13.Patients with conditions that, in the opinion of the Investigator, would prevent a careful adherence to the protocol 14.Patients with severe hypotension 15.Patients who suffer from shock (including cardiogenic shock) 16.Patients treated with Amlodipine 10 mg and Zofenopril (>30 mg or < 30 mg)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: To assess the anti-hypertensive efficacy of the extemporaneous combination of ZOF 30 mg with 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 ZOF (30 mg) or AML (5 mg) monotherapies for at least 4 weeks.;Secondary Objective: -To assess the antihypertensive efficacy of the combination of ZOF 30 mg in combination with AML 5 mg or AML 10 mg in lowering sitting systolic BP between Visit 2 and Visit 4 in patients with uncontrolled BP previously treated with ZOF 30 mg or AML 5 mg monotherapies for at least 4 weeks. -To assess the antihypertensive efficacy of the extemporaneous combination of ZOF/AML 30/10 mg vs. ZOF/AML 30/5 mg, in lowering sitting DBP and SBP between Visit 3 and Visit 4 in patients with uncontrolled BP previously treated with ZOF or AML 5 mg monotherapies for at least 4 weeks. -To evaluate the total number and percentage of patients who achieved the BP goal (sitting BP =130/80 mmHg) at Visit 2, at Visit 3 and at Visit 4. -To assess the compliance to the treatment at Visit 2, at Visit 3 and at Visit 4. -To evaluate the safety and tolerability of the monotherapies and of the extemporaneous combinations 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: The primary endpoint will be assessed before and after assessment period at Week 8, by a paired t-test using the Intention-to-treat (ITT) population and the Per-Protocol (PP) population. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in mean sitting SBP between Visit 2 (Week 0) and Visit 4 (Week 8). - Change in mean sitting DBP and SBP between Visit 3 (Week 4) and 4 (Week 8) in patients on combination of ZOF/AML 30/5 with uncontrolled BP at Visit 3 and up titrated to the extemporaneous combination of ZOF/AML 30/10 mg. - Number and proportion of patients achieving the BP goal (sitting BP=130/80 mmHg) at Visit 2 (Week 0), Visit 3 (Week 4) and Visit 4 (Week 8). - Adherence to the treatments (percentage (%) of doses taken/doses to be taken) at Visit 2 (Week 0), Visit 3 (Week 4) and Visit 4 (Week 8). - Safety and tolerability of the monotherapies (ZOF 30 mg and AML 5 mg) after 4 weeks of therapy and of the extemporaneous combination (ZOF 30 mg and AML 5 mg or AML 10 mg) after eight weeks of treatment.;Timepoint(s) of evaluation of this end point: All secondary/exploratory endpoints will be assessed before (Week 0) and after treatment (at Week 8) by a paired t-test. All secondary/exploratory endpoints related to proportion of patients achieving the BP goal at Week 4 and Week 8 will be analysed descriptively producing also the relative 95% CI to assess if there is a significant difference from Week 0 where all patients were uncontrolled. | — |
Countries
Hungary, Italy, Russian Federation
Contacts
Public ContactMedical Affairs Director Paolo Fabr
Menarini
Outcome results
None listed