Effectiveness and Safety of Combination of Amlodipine and Zofenopril in Hypertensive Patients Versus Each Monotherapy
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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      will be withdrawn from the study.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.
    

Intervention name(s): Zofenopril; Amlodipine
Intervention type(s): Drug; Drug
Intervention description(s): Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator.; Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.
Intervention MeSH terms: Amlodipine; Zofenopril
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hypertension; Combination Therapy; Zofenopril; Nebivolol; Fixed Dose Combination