To determine the dose-response of the various combinations of nifedipine GITS (gastrointestinal therapeutic system) and candesartan as compared to monotherapy and placebo based on the blood pressure (BP) lowering effects (mean seated diastolic blood pressure [MSDBP]) of a once daily regimen in subjects with World Health Organization (WHO) classification Grades 1 and 2 essential hypertension (MSDBP = 95 mmHg and < 110 mmHg). MedDRA version: 13.1 Level: PT Classification code 10015488 Term: Essen
Conditions
Interventions
Trade Name: Adalat LA 20 mg prolonged-release
tablets
Product Name: Nifedipine GITS 20 mg
Product Code: BAYa1040
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: NIFEDIPINE
CAS Numbe
Sponsors
Bayer HealthCare AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects 18 years or older. Female subjects must be either post-menopausal for one year, surgically sterile, or using an effective contraceptive method. Hormonal contraceptive use is disallowed. 2. Subjects must have mild to moderate essential hypertension (Grade 1 and 2 WHO classifications) as measured by a calibrated electronic BP measuring device (as of Amd 1). (MSDBP of = 90 mmHg and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Severe hypertension (Grade 3 WHO classification; MSDBP = 110 mmHg and/or MSSBP = 180 mmHg) - Inability to washout of antihypertensive drugs (even if prescribed for another indication) safely for a period of 14 weeks. - History of hypertensive retinopathy – known Keith-Wagener Grade III or IV - History of hypertensive encephalopathy - Cerebrovascular ischemic event (stroke, transient ischemic attack [TIA])within the previous 12 months - History of intracerebral hemorrhage or subarachnoid hemorrhage - Evidence of secondary hypertension such as coarchation of the aorta, pheochromocytoms, hypersaldosteronism, etc. - Type I diabetes mellitus (DM) or poorly controlled DM Type II as evidenced by a glycosylated hemoglobin [HbA1C] of greater than 9% on visit 1. - Allergies or known intolerance to one of the investigational drugs/drug class or to one of their ingredients - 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 1. - Clinically significant cardiac valvular disease - History of malignancy in the last 5 years, excluding basal or skin cancer - Uncorrected hypokalemia or hyperkalemia: potassium outside 3.4-5.4 mmol/L (as of Amd 1) - Surgical or medical conditions that might alter the metabolism, excretion or distribution or absorption of any drug - Gastrointestinal disease or surgery resulting in the potential for malabsorption - Severe gastrointestinal tract narrowing; kock pouch (ileostomy after proctocolectomy) - Cholestasis or biliary obstruction or history of pancreatic injury or clinical significant increase of lipase, amylase, or bilirubin. - Liver disease or AST/ALT levels > 3 x upper limit of normal (ULN) - Renal insufficiency, defined as eGFR of < 50 mL/min (computed using the Cockroft-Gault formula, see Section 7.6.2) (as of Amd 1), or on hemodialysis - Female subjects who are pregnant or lactating. - Subjects who have night employment (night shift). - Subjects with an aortic aneurysm that, in the opinion of the investigator, will be unsuitable to be enrolled in the study. - If differences greater than 20 mmHg for SBP and 10 mmHg for DBP are present on 3 consecutive BP readings, the subject should be excluded from the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the dose-response of the various combinations of nifedipine GITS (gastrointestinal therapeutic system) and candesartan as compared to monotherapy and placebo based on the blood pressure (BP) lowering effects (mean seated diastolic blood pressure [MSDBP]) of a once daily regimen in subjects with World Health Organization (WHO) classification Grades 1 and 2 essential hypertension (MSDBP = 95 mmHg and < 110 mmHg).;Secondary Objective: To confirm the best chosen dosage by tests for the responder rate, the control rate and the changes of MSDBP and mean seated systolic blood pressure (MSSBP) at week 8 from the baseline. To assess safety and tolerability of the combination product.;Primary end point(s): Primary efficacy variable is the change from baseline in MSDBP at Week 8. | — |
Countries
Belgium, Italy, Lithuania, Spain, United Kingdom
Outcome results
None listed