Effectiveness and Safety of Combination of Nebivolol and Amlodipine 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 Nebivolol 5 mg in combination with Amlodipine 5 mg or AML 10 mg in lowering the sitting
      diastolic BP after 8 weeks of treatment inpatients with uncontrolled BP previously treated
      with Nebivolol (NEB) 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.

      Grade 1 - 2 hypertensive patients [BP ranging from ≥140 to ≤179 mmHg for Systolic Blood
      Pressure (SBP) and from ≥90 to ≤109 mmHg for Diastolic Blood Pressure (DBP)] on treatment
      with any Beta Blocker (BB) or Calcium Channel Blocker (CCB), including NEB (only 5 mg dosage
      allowed) or AML (only 5 mg dosage allowed) for at least one month prior to Visit 1 will be
      screened for eligibility.

      Allowed CCBs at screening includes Felodipine, isradipine, lacidipine, lercanidipine,
      nicardipine, nifedipine, and nisoldipine. Patients treated with Amlodipine or Nebivolol in
      dosages higher than 5 mg/daily will not be eligible.

      On the same day of the Screening visit, the eligible patients will enter into a run-in period
      of 4 weeks after screening, during which:

        -  Patients receiving NEB 5 mg or AML 5 mg will continue the same therapy for 4 weeks.

        -  Patients on any other BBs or CCBs will be switched to NEB 5 mg or AML 5 mg. Patients
           entering this phase in therapy with NEB 5 mg or AML 5 mg should be in a 1:1 ratio.

      After 4 weeks (±2 days) of run-in period of monotherapy, the BP will be further assessed
      (Visit 2). Patients with uncontrolled BP levels (sitting SBP/DBP ≥130/80 mmHg) at Visit 2,
      with the treatment adherence (ranging between 80% to 120%) and who did tolerate the treatment
      will enter into the assessment period and will be assigned to the extemporaneous combination
      of NEB 5 mg and AML 5 mg. Patients with controlled BP levels (sitting SBP/DBP <130/80 mmHg)
      and/or who do not tolerate the treatment or have an adherence range below 80% or above 120%,
      will be withdrawn from the study.

      After 4 weeks ±2 days in the assessment period, patients BP will be further evaluated at
      Visit 3: patients with controlled BP levels (sitting SBP/DBP <130/80 mmHg) will continue the
      same extemporaneous combination, while patients with uncontrolled BP levels will be
      uptitrated from extemporaneous combination NEB/AML 5/5 mg to extemporaneous combination of
      NEB/AML 5/10 mg for further 4 weeks.

      At the end of the assessment period (8 weeks ±4 days), the patients will attend an End of
      Treatment Visit 4.

      To correctly evaluate the additional effect of the combination therapy, the number of
      patients with uncontrolled BP on NEB or AML monotherapy needs to be balanced at Visit 2. In
      order to maintain a 1:1 ratio during the assessment period, a cap of 110 patients for each
      treatment arm (ie. NEB and AML) will be included at Visit 2 in order to maintain a balanced
      number of uncontrolled patients entering the assessment period for each drug. The evaluation
      will be done every 50 patients. If the rate of entrance in the assessment period for one of
      the 2 tested drugs will deviate more than 5%, a corrective measure will be initiated.
    

Intervention name(s): Nebivolol; Amlodipine
Intervention type(s): Drug; Drug
Intervention description(s): 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; Nebivolol
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment