Nifedipine (Adalat CR, BAY A1040) High Dose PK/PD Study

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, 6 x 3 cross-over study. All patients who meet the entry criteria will be required to stop taking any other anti-hypertensive agents than Adalat CR (controlled release), if taken, before starting 4 weeks (±7days) open-label Adalat CR 40 mg once daily (OD) treatment phase (baseline treatment period). Of them, those who are confirmed with their eligibility as subjects for the present study at the end of the baseline treatment period will be randomly allocated to one of the 6 treatment sequences on the basis of a computer-generated randomization list. Subsequently, BAY A1040 CR tablet 40 mg OD, 40 mg twice daily (BID) or 80 mg OD will be administered to a total of 6 weeks, 2 weeks per each treatment period (Period 1-3) under double-blind conditions using BAY A1040 CR tablet 40 mg and its placebo as follows (Double-blind treatment period).

Detailed Description
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Issues on safety are addressed in the Adverse Event section.

Official Title
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Evaluation of the Efficacy, Safety, and Pharmacokinetics/Pharmacodynamics of BAY A1040 CR Tablet on High Dose Administration in Patients With Essential Hypertension.

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Nifedipine (Adalat CR, BAYA1040) 80mg OD
* Drug: Nifedipine (Adalat CR, BAYA1040) 40mg BID
* Drug: Nifedipine (Adalat CR, BAYA1040) 40mg OD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female 20 years or older and less than 75 years Outpatient Untreated or treated patients with antihypertensive agents whose blood pressure (BP) in sitting position at entry (Visit 1) is as follows. Untreated patients: systolic blood pressure (SBP) >= 160mmHg or diastolic blood pressure (DBP) >= 100mmHg Treated patients: SBP >= 140mmHg or DBP >= 90mmHg (at trough) Exclusion Criteria: Patients whose BP during baseline treatment period is: SBP>=200mmHg or DBP>=120mmHg. Patients with secondary hypertension or hypertensive emergency. Patients with cardiovascular or cerebrovascular ischemic event (stroke, transient ischemic attack (TIA), myocardial infarction or unstable angina), or with history of these within 6 months prior to the study. Patients with intracranial or subarachnoid hemorrhage, or with history of these within 6 months prior to the study. Patients with server hematopoietic dysfunction (acute/chronic leukemia, myeloma, malignant lymphoma, myelodysplastic syndrome, aplastic anemia), or with history of these.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nifedipine (Adalat CR, BAYA1040) 40 mg OD<br>Nifedipine (Adalat CR, BAYA1040) 40 milligram (mg) once daily (OD) in the morning | Drug: Nifedipine (Adalat CR, BAYA1040) 40mg OD<br>* Nifedipine (Adalat CR, BAYA1040) 40 milligram (mg) once daily (OD) in the morning<br>|
| Experimental: Nifedipine (Adalat CR, BAYA1040) 40 mg BID<br>Nifedipine (Adalat CR, BAYA1040) 40 milligram (mg) twice daily (BID). 40 mg in the morning and 40 mg in the evening | Drug: Nifedipine (Adalat CR, BAYA1040) 40mg BID<br>* Nifedipine (Adalat CR, BAYA1040) 40 milligram (mg) twice daily (BID). 40 mg in the morning and 40 mg in the evening<br>|
| Experimental: Nifedipine (Adalat CR, BAYA1040) 80 mg OD<br>Nifedipine (Adalat CR, BAYA1040) 80 milligram (mg) once daily (OD) in the morning | Drug: Nifedipine (Adalat CR, BAYA1040) 80mg OD<br>* Nifedipine (Adalat CR, BAYA1040) 80 milligram (mg) once daily (OD) in the morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Sitting Blood Pressure | Changes of sitting SBP and DBP (trough values) from baseline (ie [trough BP at the end of each period during the double-blind treatment period] minus [trough BP at the end of the baseline treatment period]) | Baseline and after 2 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences of Systolic Blood Pressure Profile | Differences in blood pressure at the same time points (0, 2, 4, 6, 8, 10, 12, 24-hour post-dose) between 2 different days (ie, end of baseline treatment period and end of 2-week treatment period) | Baseline and after 2 weeks treatment | 
| Differences of Diastolic Blood Pressure Profile | Differences in blood pressure at the same time points (0, 2, 4, 6, 8, 10, 12, 24-hour post-dose) between 2 different days (ie, end of baseline treatment period and end of 2-week treatment period) | Baseline and after 2 weeks treatment | 
| Target Blood Pressure Achievement in Elderly (≥65) | Elderly subjects (≥65 years) without diabetes mellitus or chronic renal disorders and target BP SBP <140 mm Hg and DBP <90 mm Hg | After 2 weeks treatment | 
| Target Blood Pressure Achievement in Non-elderly (<65) | Non-elderly subjects (<65 years) without diabetes mellitus or chronic renal disorder and target BP SBP <130 mm Hg and DBP <85 mm Hg | After 2 weeks treatment | 
| Target Blood Pressure Achievement in Subjects With Diabetes Mellitus or Chronic Renal Disorder | Subjects with diabetes mellitus or chronic renal disorders and target BP SBP <130 mm Hg and DBP <80 mm Hg | After 2 weeks treatment | 
| Target Blood Pressure Achievement in All Subjects | Subjects (≥65 years) without diabetes mellitus or chronic renal disorders and target BP SBP <140 mm Hg and DBP <90 mm Hg. Subjects (<65 years) without diabetes mellitus or chronic renal disorder and target BP SBP <130 mm Hg and DBP <85 mm Hg. Subjects with diabetes mellitus or chronic renal disorders and target BP SBP <130 mm Hg and DBP <80 mm Hg. | After 2 weeks treatment |