Study of Nifedipine GITS and Candesartan Combination Compared to Monotherapy in Patients With Essential Hypertension (DISTINCT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01303783
First received: February 24, 2011
Last updated: May 18, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Hypertension, Essential
Drug: Candesartan cilexetil (Atacand), 4 mg
Drug: Candesartan cilexetil (Atacand), 8 mg
Drug: Nifedipine GITS (Adalat, BAYA1040), 20 mg
Drug: Nifedipine GITS (Adalat, BAYA1040), 30 mg
Drug: Nifedipine GITS (Adalat, BAYA1040), 60 mg
Drug: Placebo
Drug: Candesartan cilexetil (Atacand), 16 mg
Drug: Candesartan cilexetil (Atacand), 32 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in mean seated systolic blood pressure (MSSBP) at Week 8 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Control rate at Week 8 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Response rate at Week 8 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Peripheral Edema [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Time to achieve first BP control [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 1381
Study Start Date: April 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 20 mg
20 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 30 mg
30 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 60 mg
60 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: Candesartan cilexetil 4 mg
Subjects received 4 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Drug: Candesartan cilexetil (Atacand), 4 mg
4 mg of candesartan as capsule
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: Candesartan cilexetil 8 mg
Subjects received 8 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Drug: Candesartan cilexetil (Atacand), 8 mg
8 mg candesartan as capsule
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: Candesartan cilexetil 16 mg
Subjects received 16 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Drug: Candesartan cilexetil (Atacand), 16 mg
16 mg of candesartan as capsule
Experimental: Candesartan cilexetil 32 mg
Subjects received 32 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Drug: Candesartan cilexetil (Atacand), 32 mg
32 mg of candesartan as capsule
Experimental: 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
Drug: Candesartan cilexetil (Atacand), 4 mg
4 mg of candesartan as capsule
Drug: Nifedipine GITS (Adalat, BAYA1040), 20 mg
20 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: 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
Drug: Candesartan cilexetil (Atacand), 8 mg
8 mg candesartan as capsule
Drug: Nifedipine GITS (Adalat, BAYA1040), 20 mg
20 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 20 mg
20 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Drug: Candesartan cilexetil (Atacand), 16 mg
16 mg of candesartan as capsule
Experimental: 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
Drug: Candesartan cilexetil (Atacand), 8 mg
8 mg candesartan as capsule
Drug: Nifedipine GITS (Adalat, BAYA1040), 30 mg
30 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 30 mg
30 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Drug: Candesartan cilexetil (Atacand), 16 mg
16 mg of candesartan as capsule
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 30 mg
30 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Drug: Candesartan cilexetil (Atacand), 32 mg
32 mg of candesartan as capsule
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 60 mg
60 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Drug: Candesartan cilexetil (Atacand), 16 mg
16 mg of candesartan as capsule
Experimental: 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
Drug: Nifedipine GITS (Adalat, BAYA1040), 60 mg
60 mg nifedipine as tablet
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses
Drug: Candesartan cilexetil (Atacand), 32 mg
32 mg of candesartan as capsule
Placebo Comparator: Placebo
Subjects received placebo (3 tablets and 1 capsule) once daily for 8 weeks
Drug: Placebo
3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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 3.0-5.0 mmol/L
  • Surgical or medical conditions that might alter the metabolism, excretion or distribution or absorption of any drug

    1. Gastrointestinal disease or surgery resulting in the potential for malabsorption
    2. Severe gastrointestinal tract narrowing; kock pouch (ileostomy after proctocolectomy)
    3. Cholestasis or biliary obstruction or history of pancreatic injury or clinical significant increase of lipase, amylase, or bilirubin.
    4. Liver disease or AST/ALT levels >3 x ULN
    5. Renal insufficiency, defined as eGFR of < 50 mL/min (computed using the Cockroft-Gault formula), or on hemodialysis
  • Investigation trial participation with receipt of investigational study drug within the last month
  • Previous assignment to treatment in this study
  • 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.
  • Thought by the investigator for any reason to be unsuitable for participation in a clinical study
  • Systemic use of known cytochrome P450-3A4 inhibitors (e.g cimetidine, anti-human immunodeficiency virus [HIV] protease inhibitors e.g. ritonavir, azole anti-mycotics eg. ketoconazole,) or inducers (e.g rifampicin, anti-epileptic drugs eg. phenytoin, carbamazepine and phenobarbitone) or some P450-3A4 substrates (e.g quinidine, digoxin, tacrolimus)
  • Present severe rhythm or conduction disorder:
  • Atrial fibrillation
  • Second or third degree heart block without a pacemaker.
  • Baseline QTc >450 msec
  • History of non-compliance, alcoholism or drug abuse that in the opinion of the investigator will compromise successful completion of 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01303783

  Show 154 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01303783     History of Changes
Other Study ID Numbers: 14725  2009-017077-37 
Study First Received: February 24, 2011
Last Updated: May 18, 2016
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Canadian Institutes of Health Research
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Lithuania: State Medicine Control Agency - Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
South Africa: Department of Health
South Korea: Ministry for Health, Welfare and Family Affairs
Spain: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: National Institute for Health Research
United States: Food and Drug Administration

Keywords provided by Bayer:
Nifedipine GITS
Candesartan
mild to moderate Hypertension
Combination therapy

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Candesartan
Candesartan cilexetil
Nifedipine
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Membrane Transport Modulators
Vasodilator Agents
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 25, 2016