Open-Label Long-Term Safety and Efficacy Study of Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Subjects With Moderate to Severe Essential Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01788358
First received: February 7, 2013
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This study examines the long term safety and efficacy of the Fixed Dose combination BAY98-7106 (nifedipine plus candesartan primarily at the highest dose in development) in patients with moderate to severe hypertension.

Patients meeting the entry criteria, will receive the Fixed Dose combination for 28 weeks, including 8 weeks with stepwise dose increase up to the high target dose. The first 200 subjects completing 28 weeks will continue treatment for additional 24 weeks (52 weeks in total).

Subjects who do not tolerate an increased dose will be treated at their highest tolerable dose.


Condition Intervention Phase
Hypertension
Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Open-Label, Long-Term Safety and Efficacy Study of the Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Adult Subjects With Moderate to Severe Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • The long-term safety and tolerability of once daily Nifedipine/Candesartan (BAY98-7106) [ Time Frame: During treatment period lasting 28 weeks ] [ Designated as safety issue: Yes ]
    The primary outcome is evaluated by incidence of all treatment-emergent adverse events; incidence of drug-related treatment-emergent adverse events; adverse events of special interest - including the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as peripheral edema, headache, and flushing) will be a particular focus.

  • The long-term safety and tolerability of once daily Nifedipine/Candesartan (BAY98-7106) [ Time Frame: During treatment period lasting 52 weeks ] [ Designated as safety issue: Yes ]
    The primary outcome is evaluated by incidence of all treatment-emergent adverse events; incidence of drug-related treatment-emergent adverse events; adverse events of special interest - including the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as peripheral edema, headache, and flushing) will be a particular focus.


Secondary Outcome Measures:
  • Change in mean seated systolic blood pressure (MSSBP) [ Time Frame: From baseline to week 28 ] [ Designated as safety issue: No ]
  • Change in mean seated systolic blood pressure (MSSBP) [ Time Frame: From baseline to week 52 ] [ Designated as safety issue: No ]
  • Change in mean seated diastolic blood pressure(MSDBP) [ Time Frame: From baseline to week 28 ] [ Designated as safety issue: No ]
  • Change in mean seated diastolic blood pressure(MSDBP) [ Time Frame: From baseline to week 52 ] [ Designated as safety issue: No ]
  • Blood pressure Response Rate [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Response rate is defined as the percentage of subjects achieving a systolic blood pressure (SBP) response (MSSBP of < 140 mmHg or a reduction of MSSBP of > 20 mmHg from baseline value), or a diastolic blood pressure (DBP) response (i.e. MSDBP of < 90 mmHg or a reduction of MSDBP of > 10 mmHg from baseline value).

  • Blood pressure Response Rate [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Response rate is defined as the percentage of subjects achieving a systolic blood pressure (SBP) response (MSSBP of < 140 mmHg or a reduction of MSSBP of > 20 mmHg from baseline value), or a diastolic blood pressure (DBP) response (i.e. MSDBP of < 90 mmHg or a reduction of MSDBP of > 10 mmHg from baseline value).

  • Blood pressure Control Rate [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Control rate is the percentage of subjects that reach the predetermined blood pressure (BP) target < 140/90 mmHg. In addition, the percentage of subjects that reach the predetermined BP target will be provided as well (BP < 140/90 mmHg for subjects without diabetes and chronic renal disorder, and BP <130/80 mmHg for subjects with diabetes or chronic renal disorder).

  • Blood pressure Control Rate [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Control rate is the percentage of subjects that reach the predetermined blood pressure (BP) target < 140/90 mmHg. In addition, the percentage of subjects that reach the predetermined BP target will be provided as well (BP < 140/90 mmHg for subjects without diabetes and chronic renal disorder, and BP <130/80 mmHg for subjects with diabetes or chronic renal disorder).


Enrollment: 507
Study Start Date: February 2013
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nifedipine/Candesartan
Treatment with 1 tablet once daily in the morning for 28 or 52 weeks. In the initial 8 weeks the dose will be increased stepwise from low starting doses up to the high target dose (Nifedipine / Candesartan 60/32 mg)
Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/8 mg, orally once daily
Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/16 mg, orally once daily
Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/16 mg, orally once daily
Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/32 mg, orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have moderate to severe essential hypertension (Grade 2 or Grade 3, WHO classifications). At Visit 1, subjects not treated with antihypertensive medications are to have MSSBP of >/= 160 mmHg and < 200 mmHg, as measured by a calibrated electronic BP measuring device. For other subjects who are treated with antihypertensive medication before, they should have MSSBP >/= 160 mmHg and <200 mmHg after wash out.
  • Women of childbearing potential and men must agree to use adequate contraception other than hormonal contraceptives when sexually active

Exclusion Criteria:

  • Mean seated systolic blood pressure >/= 200 mmHg and/or mean seated diastolic blood pressure >/= 120 mm/Hg
  • Mean seated diastolic blood pressure < 60 mm/Hg
  • Differences greater than 20 mmHg for systolic blood pressure and 10 mmHg for diastolic blood pressure are present on 3 consecutive blood pressure readings at visit 0
  • Any history of hypertensive emergency
  • Evidence of secondary hypertension such as coarctation of the aorta, pheochromocytoma, hyperaldosteronism, etc.
  • Cerebrovascular ischemic event (stroke, transient ischemic attack [TIA])within the previous 12 months
  • History of intracerebral hemorrhage or subarachnoid hemorrhage
  • History of hypertensive retinopathy - known Keith-Wagener Grade III or IV
  • 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 0
  • Type 1 diabetes mellitus (DM) or poorly controlled Type 2 DM as evidenced by HbA1C of greater than 9% on visit 0.
  • Hyperkalemia: potassium above the upper limit of normal in the laboratory range
  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: NCT01788358

  Hide Study Locations
Locations
United States, Alabama
Foley, Alabama, United States, 36535
United States, California
Carmichael, California, United States, 95608
Los Angeles, California, United States, 90057
Spring Valley, California, United States, 91978
United States, Connecticut
Milford, Connecticut, United States, 06460
United States, Florida
Coral Gables, Florida, United States, 33114-4192
Hallandale Beach, Florida, United States, 33009
Hollywood, Florida, United States, 33083
Jacksonville, Florida, United States, 32216
Jupiter, Florida, United States, 33458
Tampa, Florida, United States, 33606
United States, Georgia
Atlanta, Georgia, United States, 30338
United States, Indiana
Valparaiso, Indiana, United States, 46383
United States, Kansas
Newton, Kansas, United States, 67114
Wichita, Kansas, United States, 67205
United States, Kentucky
Lexington, Kentucky, United States, 40504
United States, Louisiana
New Orleans, Louisiana, United States, 70119
United States, Maine
Auburn, Maine, United States, 04240
United States, Maryland
Elkridge, Maryland, United States, 21075
United States, Massachusetts
Brockton, Massachusetts, United States, 02301
United States, Missouri
St. Louis, Missouri, United States, 63141
United States, North Carolina
Shelby, North Carolina, United States, 28150
United States, Ohio
Cincinnati, Ohio, United States, 45224
Cincinnati, Ohio, United States, 45245
Cincinnati, Ohio, United States, 45246
Columbus, Ohio, United States, 43213
United States, South Carolina
Greenville, South Carolina, United States, 29615
Mt. Pleasant, South Carolina, United States, 29464
United States, South Dakota
Rapid City, South Dakota, United States, 57702
United States, Tennessee
Nashville, Tennessee, United States, 37203
New Tazewell, Tennessee, United States, 37825
United States, Texas
Beaumont, Texas, United States, 77701
Bryan, Texas, United States, 77802
Carrollton, Texas, United States, 75010
Dallas, Texas, United States, 75230
San Antonio, Texas, United States, 78229
United States, Utah
Salt Lake City, Utah, United States, 84121
Salt Lake City, Utah, United States, 84109
United States, Wisconsin
Kenosha, Wisconsin, United States, 53142
Belgium
Moorsel, Oost-Vlaanderen, Belgium, 9310
Wetteren, Oost-Vlaanderen, Belgium, 9230
Steenokkerzeel, Vlaams Brabant, Belgium, 1820
Deurne, Belgium, 2100
HAM, Belgium, 3545
Canada, British Columbia
Burnaby, British Columbia, Canada, V5G 1T4
Langley, British Columbia, Canada, V3A 4H9
Vancouver, British Columbia, Canada, V5Z 1K3
Canada, Ontario
Brampton, Ontario, Canada, L6T 0G1
Burlington, Ontario, Canada, L7M 4Y1
Etobicoke, Ontario, Canada, M8V 3X8
London, Ontario, Canada, N5W 6A2
Newmarket, Ontario, Canada, L3Y 5G8
Sarnia, Ontario, Canada, N7T 4X3
Stayner, Ontario, Canada, L0M 1S0
Toronto, Ontario, Canada, M4S 1Y2
Toronto, Ontario, Canada, M9V 4B4
Woodstock, Ontario, Canada, N4S 4G3
Canada, Quebec
Pointe-Claire, Quebec, Canada, H9R 3J1
Ste-Foy, Quebec, Canada, G1W 1S2
Germany
Frankfurt, Hessen, Germany, 60596
Bochum, Nordrhein-Westfalen, Germany, 44787
Magdeburg, Sachsen-Anhalt, Germany, 39104
Görlitz, Sachsen, Germany, 02826
Leipzig, Sachsen, Germany, 04103
Berlin, Germany, 12627
Dresden, Germany
Poland
Gdynia, Poland, 81-384
Katowice, Poland, 40-040
Warszawa, Poland, 01-192
Wroclaw, Poland, 50-088
United Kingdom
Reading, Berkshire, United Kingdom, RG2 0TG
Chesterfield, Derbyshire, United Kingdom, S40 4AA
Blackpool, Lancashire, United Kingdom, FY3 7EN
Bath, Somerset, United Kingdom, BA3 2UH
Bury St Edmonds, Suffolk, United Kingdom, IP30 9QU
Coventry, Warwickshire, United Kingdom, CV6 4DD
Birmingham, West Midlands, United Kingdom, B15 2SQ
Cardiff, United Kingdom, CF14 5GJ
Chorley, United Kingdom, PR7 7NA
Glasgow, United Kingdom, G20 OSP
Liverpool, United Kingdom, L22 0LG
Manchester, United Kingdom, M15 6SX
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01788358     History of Changes
Other Study ID Numbers: 14801, 2012-004515-32
Study First Received: February 7, 2013
Last Updated: July 28, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Bayer:
Drug combination
Nifedipine GITS
Candesartan Cilexetil
Hypertension
Combination therapy

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

ClinicalTrials.gov processed this record on August 01, 2014