Open-Label Long-Term Safety and Efficacy Study of Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Subjects With Moderate to Severe Essential Hypertension

• The long-term safety and tolerability of once daily Nifedipine/Candesartan (BAY98-7106) [ Time Frame: During treatment period lasting 28 weeks ] [ Designated as safety issue: Yes ]
  The primary outcome is evaluated by incidence of all treatment-emergent adverse events; incidence of drug-related treatment-emergent adverse events; adverse events of special interest - including the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as peripheral edema, headache, and flushing) will be a particular focus.
• The long-term safety and tolerability of once daily Nifedipine/Candesartan (BAY98-7106) [ Time Frame: During treatment period lasting 52 weeks ] [ Designated as safety issue: Yes ]
  The primary outcome is evaluated by incidence of all treatment-emergent adverse events; incidence of drug-related treatment-emergent adverse events; adverse events of special interest - including the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as peripheral edema, headache, and flushing) will be a particular focus.

• Change in mean seated systolic blood pressure (MSSBP) [ Time Frame: From baseline to week 28 ] [ Designated as safety issue: No ]
• Change in mean seated systolic blood pressure (MSSBP) [ Time Frame: From baseline to week 52 ] [ Designated as safety issue: No ]
• Change in mean seated diastolic blood pressure(MSDBP) [ Time Frame: From baseline to week 28 ] [ Designated as safety issue: No ]
• Change in mean seated diastolic blood pressure(MSDBP) [ Time Frame: From baseline to week 52 ] [ Designated as safety issue: No ]
• Blood pressure Response Rate [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Response rate is defined as the percentage of subjects achieving a systolic blood pressure (SBP) response (MSSBP of < 140 mmHg or a reduction of MSSBP of > 20 mmHg from baseline value), or a diastolic blood pressure (DBP) response (i.e. MSDBP of < 90 mmHg or a reduction of MSDBP of > 10 mmHg from baseline value).
• Blood pressure Response Rate [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  Response rate is defined as the percentage of subjects achieving a systolic blood pressure (SBP) response (MSSBP of < 140 mmHg or a reduction of MSSBP of > 20 mmHg from baseline value), or a diastolic blood pressure (DBP) response (i.e. MSDBP of < 90 mmHg or a reduction of MSDBP of > 10 mmHg from baseline value).
• Blood pressure Control Rate [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  Control rate is the percentage of subjects that reach the predetermined blood pressure (BP) target < 140/90 mmHg. In addition, the percentage of subjects that reach the predetermined BP target will be provided as well (BP < 140/90 mmHg for subjects without diabetes and chronic renal disorder, and BP <130/80 mmHg for subjects with diabetes or chronic renal disorder).
• Blood pressure Control Rate [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  Control rate is the percentage of subjects that reach the predetermined blood pressure (BP) target < 140/90 mmHg. In addition, the percentage of subjects that reach the predetermined BP target will be provided as well (BP < 140/90 mmHg for subjects without diabetes and chronic renal disorder, and BP <130/80 mmHg for subjects with diabetes or chronic renal disorder).

This study examines the long term safety and efficacy of the Fixed Dose combination BAY98-7106 (nifedipine plus candesartan primarily at the highest dose in development) in patients with moderate to severe hypertension.

Patients meeting the entry criteria, will receive the Fixed Dose combination for 28 weeks, including 8 weeks with stepwise dose increase up to the high target dose. The first 200 subjects completing 28 weeks will continue treatment for additional 24 weeks (52 weeks in total).

Subjects who do not tolerate an increased dose will be treated at their highest tolerable dose.

• Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
  Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/8 mg, orally once daily
• Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
  Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/16 mg, orally once daily
• Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
  Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/16 mg, orally once daily
• Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
  Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/32 mg, orally once daily

Inclusion Criteria:

• Subjects must have moderate to severe essential hypertension (Grade 2 or Grade 3, WHO classifications). At Visit 1, subjects not treated with antihypertensive medications are to have MSSBP of >/= 160 mmHg and < 200 mmHg, as measured by a calibrated electronic BP measuring device. For other subjects who are treated with antihypertensive medication before, they should have MSSBP >/= 160 mmHg and <200 mmHg after wash out.
• Women of childbearing potential and men must agree to use adequate contraception other than hormonal contraceptives when sexually active

Exclusion Criteria:

• Mean seated systolic blood pressure >/= 200 mmHg and/or mean seated diastolic blood pressure >/= 120 mm/Hg
• Mean seated diastolic blood pressure < 60 mm/Hg
• Differences greater than 20 mmHg for systolic blood pressure and 10 mmHg for diastolic blood pressure are present on 3 consecutive blood pressure readings at visit 0
• Any history of hypertensive emergency
• Evidence of secondary hypertension such as coarctation of the aorta, pheochromocytoma, hyperaldosteronism, etc.
• Cerebrovascular ischemic event (stroke, transient ischemic attack [TIA])within the previous 12 months
• History of intracerebral hemorrhage or subarachnoid hemorrhage
• History of hypertensive retinopathy - known Keith-Wagener Grade III or IV
• Any history of heart failure, New York Heart Association (NYHA) classification III or IV
• Severe coronary heart disease as manifest by a history of myocardial infarction or unstable angina in the last 6 months prior to visit 0
• Type 1 diabetes mellitus (DM) or poorly controlled Type 2 DM as evidenced by HbA1C of greater than 9% on visit 0.
• Hyperkalemia: potassium above the upper limit of normal in the laboratory range