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

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

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).

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Nifedipine (Adalat CR, BAYA1040) 40mg OD; Drug: Nifedipine (Adalat CR, BAYA1040) 40mg BID; Drug: Nifedipine (Adalat CR, BAYA1040) 80mg OD

Detailed Description

Issues on safety are addressed in the Adverse Event section.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Miyagi
    • Sendai, Miyagi, Japan, 982-0032
  • Osaka
    • Suita, Osaka, Japan, 565-0853
  • Saitama
    • Koshigaya, Saitama, Japan, 343-0827

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: October 7, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Estimate): June 8, 2015
• Last Update Submitted That Met QC Criteria: May 13, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine
• Other Study ID Numbers: 13012