Fixed Dose Combination of Bisoprolol and Amlodipine in the Treatment of Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Bisoprolol/Amlodipine (Bisoprolol failed group); Bisoprolol/Amlodipine (Amlodipine failed group)
Intervention description: Bisoprolol/Amlodipine FDC tablet will be orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If blood pressure (BP) is controlled at Week 6 (Day 43), the same dose will continue for next 6 weeks. If the BP is not controlled at Day 43, the dose will be increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks. Subjects who have controlled BP at Week 12 (Day 85), will continue with the same dose for next 6 weeks. If their BP is not controlled at Day 85, dose will be increased to the next level (Bisoprolol/Amlodipine 5mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/5mg dose and Bisoprolol/Amlodipine and 10mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18 (Day 127).; Bisoprolol/Amlodipine FDC tablet will be orally administered at an initial dose of 5 milligram (mg)/5 mg once daily for 6 weeks. If BP is controlled at Week 6 (Day 43), the same dose will continue for next 6 weeks. If the BP is not controlled at Day 43, the dose will be increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks. Subjects who have controlled BP at Week 12 (Day 85), will continue with the same dose for next 6 weeks. If their BP is not controlled at Day 85, dose will be increased to the next level (Bisoprolol/Amlodipine 5mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/5mg dose and Bisoprolol/Amlodipine and 10mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18 (Day 127).
Intervention MeSH terms: Amlodipine; Bisoprolol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 200.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bisoprolol; Amlodipine; Fixed dose combination (FDC); Systolic Blood Pressure (SBP); Diastolic Blood Pressure (DBP)

Summary:

      This is a randomized, comparative Phase 3 trial to investigate the efficacy of fixed dose
      combination (FDC) of bisoprolol and amlodipine in hypertensive subjects (superiority of FDC
      over monotherapies).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Essential hypertension not controlled at 5 mg bisoprolol or 5 mg amlodipine at least 4
             weeks (definition of not controlled: SBP greater than or equal to (>=) 140 millimeter
             of mercury (mmHg) with or without DBP >= 90 mmHg)

          -  Male or female subjects >=18 years of age, without limitation on race

          -  Medically accepted effective contraception if procreative potential exists (applicable
             for both male and female subjects until at least 90 days after the last dose of trial
             treatment)

          -  Subjects who have signed the informed consent form before any trial related assessment

        Exclusion Criteria:

          -  General contraindications of beta-blockers and/or calcium channel blockers

               -  Previous and concurrent acute heart failure or during episodes of heart failure
                  decompensation requiring intravenous inotropic therapy

               -  Concurrent cardiogenic shock

               -  Previous and concurrent second or third degree atrioventricular (AV) block
                  (without a pacemaker)

               -  Previous and concurrent sick sinus syndrome

               -  Previous and concurrent sinoatrial block

               -  Concurrent symptomatic bradycardia

               -  Concurrent symptomatic hypotension

               -  Previous and concurrent severe bronchial asthma or chronic obstructive pulmonary
                  diseases

               -  Previous and concurrent severe peripheral arterial occlusive diseases and
                  Raynaud's syndrome

               -  Untreated pheochromocytoma

               -  Concurrent metabolic acidosis

               -  Known hypersensitivity to bisoprolol, amlodipine, dihydropyridine derivates or to
                  any of the excipients

          -  Seated pulse rate less than 60 beats per minute (bpm) at screening

          -  Any other anti-hypertensive drugs (other than bisoprolol and amlodipine) are used
             within 4 weeks prior to the screening visit

          -  Use of any enzyme-modifying drugs acting on cytochrome P450 (CYP) 3A4 enzymes via
             inhibition (such as ketoconazole, itraconazole, ritonavir) or induction (such as
             rifampicin or hypericum perforatum) within 28 days before Day 1 of the trial

          -  Other significant disease that in the Investigator's opinion that would exclude the
             subject from the trial, such as uncontrolled diabetes mellitus, severe liver and/or
             kidney dysfunction, decompensated cardiac failure

          -  Any other condition or therapy which in the Investigator's opinion would pose a risk
             to the subject or interfere with the trial objectives

          -  Concurrent alcohol and/or drug abuse

          -  Known hypersensitivity to the trial treatments

          -  Pregnancy and lactation period. All female subjects with reproductive potential must
             have a negative pregnancy serum test within the 7 days prior to enrollment

          -  Known lack of subject compliance

          -  Legal incapacity or limited legal capacity

          -  Participation in another clinical trial within the previous 30 days

          -  Persons directly involved in the execution of the protocol