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

NCT01788358 | Completed Phase 3 Results

• 2 other identifiers: 148012012-004515-32
• Study Type: interventional
• Target: 508
• Locations: 6 countries
• Sites: 82

Brief Summary

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.

Conditions

Hypertension

Keywords

Drug combination; Nifedipine GITS; Candesartan Cilexetil; Hypertension; Combination therapy

Outcome Measures

Primary Outcomes (4)

• Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 28

  An adverse event (AE) is any untoward medical occurrence (that is, any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.

  From the time of first study drug administration up to Week 28

• Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 28

  An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.

  From the time of first study drug administration up to Week 28

• Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 52/End of Study (EOS)

  An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.

  From the time of first study drug administration up to Week 52/EOS

• Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 52/End of Study (EOS)

  An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.

  From the time of study treatment up to Week 52/EOS

Secondary Outcomes (5)

• Number of Subjects With Clinically Relevant Changes in Laboratory Parameters

  Baseline (Week 0) up to Week 52/EOS

• Change From Baseline In Mean Seated Systolic Blood Pressure (MSSBP) At Weeks 28 And 52

  Baseline (Week 0), Weeks 28 and 52

• Change From Baseline in Mean Seated Diastolic Blood Pressure (MSDBP) at Weeks 28 and 52

  Baseline (Week 0), Weeks 28 and 52

• Blood Pressure Control Rate at Weeks 28 and 52

  Weeks 28 and 52

• Blood Pressure Response Rate at Weeks 28 and 52

  Weeks 28 and 52

Study Arms (1)

Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)

EXPERIMENTAL

Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram \[mg\] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).

Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)

Interventions

Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106) DRUG

Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/8 mg, orally once daily

Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (82)

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Foley, Alabama, 36535, United States

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Carmichael, California, 95608, United States

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Los Angeles, California, 90057, United States

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Spring Valley, California, 91978, United States

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Milford, Connecticut, 06460, United States

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Coral Gables, Florida, 33114-4192, United States

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Hallandale, Florida, 33009, United States

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Hollywood, Florida, 33083, United States

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Jacksonville, Florida, 32216, United States

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Jupiter, Florida, 33458, United States

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Tampa, Florida, 33606, United States

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Atlanta, Georgia, 30338, United States

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Valparaiso, Indiana, 46383, United States

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Newton, Kansas, 67114, United States

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Wichita, Kansas, 67205, United States

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Lexington, Kentucky, 40504, United States

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New Orleans, Louisiana, 70119, United States

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Auburn, Maine, 04240, United States

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Elkridge, Maryland, 21075, United States

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Brockton, Massachusetts, 02301, United States

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St Louis, Missouri, 63141, United States

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Shelby, North Carolina, 28150, United States

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Cincinnati, Ohio, 45224, United States

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Cincinnati, Ohio, 45245, United States

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Cincinnati, Ohio, 45246, United States

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Columbus, Ohio, 43213, United States

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Greenville, South Carolina, 29615, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Rapid City, South Dakota, 57702, United States

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Nashville, Tennessee, 37203, United States

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New Tazewell, Tennessee, 37825, United States

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Beaumont, Texas, 77701, United States

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Bryan, Texas, 77802, United States

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Carrollton, Texas, 75010, United States

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Dallas, Texas, 75230, United States

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San Antonio, Texas, 78229, United States

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Salt Lake City, Utah, 84109, United States

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Salt Lake City, Utah, 84121, United States

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Kenosha, Wisconsin, 53142, United States

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Moorsel, Oost-Vlaanderen, 9310, Belgium

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Wetteren, Oost-Vlaanderen, 9230, Belgium

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Steenokkerzeel, Vlaams Brabant, 1820, Belgium

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Deurne, 2100, Belgium

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Ham, 3545, Belgium

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Burnaby, British Columbia, V5G 1T4, Canada

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Langley, British Columbia, V3A 4H9, Canada

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Vancouver, British Columbia, V5Z 1K3, Canada

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Brampton, Ontario, L6T 0G1, Canada

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Burlington, Ontario, L7M 4Y1, Canada

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Etobicoke, Ontario, M8V 3X8, Canada

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London, Ontario, N5W 6A2, Canada

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Newmarket, Ontario, L3Y 5G8, Canada

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Sarnia, Ontario, N7T 4X3, Canada

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Stayner, Ontario, L0M 1S0, Canada

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Toronto, Ontario, M4S 1Y2, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Woodstock, Ontario, N4S 4G3, Canada

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Pointe-Claire, Quebec, H9R 3J1, Canada

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Ste-Foy, Quebec, G1W 1S2, Canada

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Frankfurt am Main, Hesse, 60313, Germany

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Bochum, North Rhine-Westphalia, 44787, Germany

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Görlitz, Saxony, 02826, Germany

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Leipzig, Saxony, 04103, Germany

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Magdeburg, Saxony-Anhalt, 39104, Germany

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Berlin, 12627, Germany

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Dresden, Germany

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Gdynia, 81-384, Poland

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Katowice, 40-040, Poland

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Warsaw, 01-192, Poland

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Wroclaw, 50-088, Poland

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Reading, Berkshire, RG2 0TG, United Kingdom

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Chesterfield, Derbyshire, S40 4AA, United Kingdom

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Blackpool, Lancashire, FY3 7EN, United Kingdom

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Bath, Somerset, BA3 2UH, United Kingdom

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Bury Saint Edmonds, Suffolk, IP30 9QU, United Kingdom

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Coventry, Warwickshire, CV6 4DD, United Kingdom

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Birmingham, West Midlands, B15 2SQ, United Kingdom

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Cardiff, CF14 5GJ, United Kingdom

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Chorley, PR7 7NA, United Kingdom

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Glasgow, G20 OSP, United Kingdom

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Liverpool, L22 0LG, United Kingdom

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Manchester, M15 6SX, United Kingdom

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Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer HealthCare AG

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2013
• First Posted: February 11, 2013
• Study Start: February 14, 2013
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: October 24, 2017
• Results First Posted: August 17, 2015

Record last verified: 2017-09

Locations

DE (7); BE (5); US (39); PL (4); GB (12); CA (15)