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

• ClinicalTrials.gov Identifier: NCT00768560
• Recruitment Status: Completed
• First Posted: October 8, 2008
• Results First Posted: February 2, 2010
• Last Update Posted: June 8, 2015
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Nifedipine (Adalat CR, BAYA1040) 80mg OD; Drug: Nifedipine (Adalat CR, BAYA1040) 40mg BID; Drug: Nifedipine (Adalat CR, BAYA1040) 40mg OD	Phase 2

Detailed Description:

Issues on safety are addressed in the Adverse Event section.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Efficacy, Safety, and Pharmacokinetics/Pharmacodynamics of BAY A1040 CR Tablet on High Dose Administration in Patients With Essential Hypertension.
• Study Start Date: January 2008
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: May 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change of Sitting Blood Pressure [ Time Frame: Baseline and after 2 weeks treatment ]
   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])

Secondary Outcome Measures :

1. Differences of Systolic Blood Pressure Profile [ Time Frame: Baseline and after 2 weeks treatment ]
   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)
2. Differences of Diastolic Blood Pressure Profile [ Time Frame: Baseline and after 2 weeks treatment ]
   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)
3. Target Blood Pressure Achievement in Elderly (≥65) [ Time Frame: After 2 weeks treatment ]
   Elderly subjects (≥65 years) without diabetes mellitus or chronic renal disorders and target BP SBP <140 mm Hg and DBP <90 mm Hg
4. Target Blood Pressure Achievement in Non-elderly (<65) [ Time Frame: After 2 weeks treatment ]
   Non-elderly subjects (<65 years) without diabetes mellitus or chronic renal disorder and target BP SBP <130 mm Hg and DBP <85 mm Hg
5. Target Blood Pressure Achievement in Subjects With Diabetes Mellitus or Chronic Renal Disorder [ Time Frame: After 2 weeks treatment ]
   Subjects with diabetes mellitus or chronic renal disorders and target BP SBP <130 mm Hg and DBP <80 mm Hg
6. Target Blood Pressure Achievement in All Subjects [ Time Frame: After 2 weeks treatment ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Japan

Sendai, Miyagi, Japan, 982-0032

Suita, Osaka, Japan, 565-0853

Koshigaya, Saitama, Japan, 343-0827

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00768560
• Other Study ID Numbers: 13012
• First Posted: October 8, 2008
• Results First Posted: February 2, 2010
• Last Update Posted: June 8, 2015
• Last Verified: May 2015

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Nifedipine; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents; Tocolytic Agents; Reproductive Control Agents