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

Bayer35 enrolled

Overview

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).

Issues on safety are addressed in the Adverse Event section.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hypertension

Interventions

Eligibility

Sex: ALLMin age: 20 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (3)

Unnamed facility

Sendai, Miyagi, Japan

Unnamed facility

Suita, Osaka, Japan

Unnamed facility

Koshigaya, Saitama, Japan

Outcomes

Primary Outcomes

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 \[trough BP at the end of the baseline treatment period\])

Time frame: Baseline and after 2 weeks treatment

Secondary Outcomes

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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: After 2 weeks treatment