Fixed Dose Combination of Bisoprolol and Amlodipine in the Treatment of Hypertension

A Randomized, Comparative Trial of Concor AM, a Fixed Dose Combination of Bisoprolol and Amlodipine, on the Treatment of Essential Hypertensive Patients Whose Blood Pressure is Not Well Controlled by Monotherapy of Bisoprolol 5mg or Amlodipine 5mg

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).

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