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

Approximately 290 patients are planned to be screened to ensure at least 216 patients complete the run-in period and start with the assessment period. Patients with Grade 1-2 hypertensive patients (blood pressure \[BP\] ranging from ≥140/90 mmHg to ≤179/109 mmHg) on treatment with any angiotensin converting enzyme inhibitors (ACE-i) including Zofenopril (ZOF)30 mg or with calcium channel blockers (CCBs) including Amlodipine (AML)5 mg will be screened for eligibility (Visit 1). Allowed CCBs: Felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, and nisoldipine. Patients treated with other dosages of ZOF (other than 30 mg) are not allowed to be screened. After screening, on the same day, eligible patients, will enter into a 4-week run-in period, during which patients on other ACE-i will be assigned to monotherapy with ZOF 30 mg while patients on CCBs will be assigned to monotherapy with AML 5 mg for 4 weeks. Patients with on-going treatment zofenopril 30 mg and amlodipine 5mg will continue on the same treatment for 4 weeks. After the run-in period (4 weeks ± 2 days), BP will be further assessed (Visit 2), if BP levels are over the defined controlled target goal, sitting Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) \>130/80 mmHg, treatment is well tolerated and adherence to the treatments ranges from 80% to 120%, patients will enter the assessment period, where they will be assigned to the extemporaneous combination of ZOF 30 mg and AML 5 mg. At Visit 2 patients with SBP/DBP values classified as Grade 3 (SBP ≥ 180 or DBP ≥ 110 mmHg) hypertension will be withdrawn from the study. If patients, at Visit 2, after the run-in period, have a controlled BP (sitting SBP/DBP≤130/80 mmHg) or do not tolerate the treatment or have an adherence range below 80% or superior to 120%, they will be withdrawn from the study. The patients will be assessed for further 8 weeks (assessment period). After 4 weeks ± 2 days from Visit 2,during the assessment period patients receiving the extemporaneous combination of ZOF 30 mg and AML 5 mg, will be further evaluated (Visit 3): controlled patients (sitting SBP/DBP ≤130/80 mmHg) will continue the same extemporaneous combination for additional 4 weeks ± 2 days, while uncontrolled patients (sitting SBP/DBP \>130/80 mmHg) will be up-titrated from ZOF/AML 30/5 mg to ZOF/AML 30/10 mg for further 4 weeks ± 2 days. At Visit 3 patients with SBP/DBP values classified as Grade 3 (SBP ≥ 180 or DBP ≥ 110 mmHg) hypertension will be withdrawn from the study. If patients at Visit 3, do not tolerate the extemporaneous combination treatment or they have an adherence range below 80% or superior to 120%, they will be withdrawn from the study. At the end of the assessment period (8 weeks ± 4 days) at Visit 4, the anti-hypertensive effect of the extemporaneous combination (ZOF/AML 30/5 mg and ZOF/AML 30/10 mg) will be evaluated. Efforts will be made to achieve 1:1 ratio in the enrolment of patients receiving any ACE-i or allowed CCBs (refer to section Subject Study Phases Duration for allowed CCBs). At Visit 2, a minimum of 45% of uncontrolled patients receiving treatment with ZOF 30 mg or AML 5 mg are required to enter the assessment period, in order to maintain a balance between the 2 treatments during the assessment period.