A Multicenter, Multifactorial, Randomized, Double-Blind, Placebo-Controlled Dose-Finding Study of Nifedipine GITS and Candesartan in Combination Compared to Monotherapy in Adult Patients With Essential Hypertension
Overview
- Phase
- Phase 2
- Intervention
- Nifedipine GITS (Adalat, BAYA1040), 20 mg
- Conditions
- Hypertension, Essential
- Sponsor
- Bayer
- Enrollment
- 1381
- Primary Endpoint
- The primary efficacy variable is the change from baseline in mean seated diastolic blood pressure (MSDBP) at Week 8
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to determine the blood pressure lowering responses of various dose combinations of nifedipine GITS and candesartan as compared to treatment with each component on their own (monotherapy) and placebo (a look-alike tablet without active ingredient). The drugs - nifedipine GITS and candesartan - which are being investigated are currently approved for use in patients with essential hypertension alone or together with other antihypertensive drugs (combination therapy), but the optimal dose of nifedipine GITS and candesartan used together in the treatment of essential hypertension has not been established yet. In this study patients will be treated with various doses of nifedipine GITS and/or candesartan or placebo. These different regimens will be administered once a day and will be assessed based on their blood pressure lowering effects (mean sitting diastolic blood pressure) in subjects with mild to moderate essential hypertension.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Subjects must have mild to moderate essential hypertension (Grade 1 and 2 WHO classifications) as measured by calibrated standard sphygmomanometer. (MSDBP of ≥90 mmHg and \< 110 mmHg at Visit 1 (placebo run-in), and MSDBP of ≥95 mmHg and \< 110 mmHg at visit 2 (randomization)
- •Subjects must have an absolute difference in their MSDBP of less than 10 mmHg between Visit 1 (placebo run- in) and Visit 2 (randomization).
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
- •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
Arms & Interventions
Nifedipine GITS 20 mg
Subjects received 20 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule
Intervention: Nifedipine GITS (Adalat, BAYA1040), 20 mg
Nifedipine GITS 20 mg
Subjects received 20 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule
Intervention: Placebo
Nifedipine GITS 30 mg
Subjects received 30 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule
Intervention: Nifedipine GITS (Adalat, BAYA1040), 30 mg
Nifedipine GITS 30 mg
Subjects received 30 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule
Intervention: Placebo
Nifedipine GITS 60 mg
Subjects received 60 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule
Intervention: Nifedipine GITS (Adalat, BAYA1040), 60 mg
Nifedipine GITS 60 mg
Subjects received 60 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule
Intervention: Placebo
Candesartan cilexetil 4 mg
Subjects received 4 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 4 mg
Candesartan cilexetil 4 mg
Subjects received 4 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Placebo
Candesartan cilexetil 8 mg
Subjects received 8 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 8 mg
Candesartan cilexetil 8 mg
Subjects received 8 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Placebo
Candesartan cilexetil 16 mg
Subjects received 16 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Placebo
Candesartan cilexetil 16 mg
Subjects received 16 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 16 mg
Candesartan cilexetil 32 mg
Subjects received 32 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Placebo
Candesartan cilexetil 32 mg
Subjects received 32 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 32 mg
Nifedipine/candesartan 20/4 mg
Subjects received the combination of 20 mg of nifedipine GITS/4 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 4 mg
Nifedipine/candesartan 20/4 mg
Subjects received the combination of 20 mg of nifedipine GITS/4 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 20 mg
Nifedipine/candesartan 20/4 mg
Subjects received the combination of 20 mg of nifedipine GITS/4 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Nifedipine/candesartan 20/8 mg
Subjects received the combination of 20 mg of nifedipine GITS/8 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 8 mg
Nifedipine/candesartan 20/8 mg
Subjects received the combination of 20 mg of nifedipine GITS/8 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 20 mg
Nifedipine/candesartan 20/8 mg
Subjects received the combination of 20 mg of nifedipine GITS/8 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Nifedipine/candesartan 60/32 mg
Subjects received the combination of 60 mg of nifedipine GITS/32 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 60 mg
Nifedipine/candesartan 60/32 mg
Subjects received the combination of 60 mg of nifedipine GITS/32 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Nifedipine/candesartan 20/16 mg
Subjects received the combination of 20 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 20 mg
Nifedipine/candesartan 20/16 mg
Subjects received the combination of 20 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Nifedipine/candesartan 60/32 mg
Subjects received the combination of 60 mg of nifedipine GITS/32 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 32 mg
Nifedipine/candesartan 20/16 mg
Subjects received the combination of 20 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 16 mg
Nifedipine/candesartan 30/8 mg
Subjects received the combination of 30 mg of nifedipine GITS/8 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 8 mg
Nifedipine/candesartan 30/8 mg
Subjects received the combination of 30 mg of nifedipine GITS/8 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 30 mg
Nifedipine/candesartan 30/8 mg
Subjects received the combination of 30 mg of nifedipine GITS/8 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Placebo
Subjects received placebo (3 tablets and 1 capsule) once daily for 8 weeks
Intervention: Placebo
Nifedipine/candesartan 30/16 mg
Subjects received the combination of 30 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 30 mg
Nifedipine/candesartan 30/16 mg
Subjects received the combination of 30 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Nifedipine/candesartan 30/16 mg
Subjects received the combination of 30 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 16 mg
Nifedipine/candesartan 30/32 mg
Subjects received the combination of 30 mg of nifedipine GITS/32 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 30 mg
Nifedipine/candesartan 30/32 mg
Subjects received the combination of 30 mg of nifedipine GITS/32 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Nifedipine/candesartan 30/32 mg
Subjects received the combination of 30 mg of nifedipine GITS/32 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 32 mg
Nifedipine/candesartan 60/16 mg
Subjects received the combination of 60 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Nifedipine GITS (Adalat, BAYA1040), 60 mg
Nifedipine/candesartan 60/16 mg
Subjects received the combination of 60 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Placebo
Nifedipine/candesartan 60/16 mg
Subjects received the combination of 60 mg of nifedipine GITS/16 mg of candesartan cilexetil once daily for 8 weeks along with 2 placebo tablets
Intervention: Candesartan cilexetil (Atacand), 16 mg
Outcomes
Primary Outcomes
The primary efficacy variable is the change from baseline in mean seated diastolic blood pressure (MSDBP) at Week 8
Time Frame: Baseline taken at Visit 1; primary outcome variable assesed at 8 weeks
Secondary Outcomes
- Change in mean seated systolic blood pressure (MSSBP) at Week 8(8 weeks)
- Time to achieve first BP control(8 weeks)
- Control rate at Week 8(8 weeks)
- Response rate at Week 8(8 weeks)
- Peripheral Edema(8 weeks)