check_circleStudy Completed

Hypertension, essential

Study of Nifedipine GITS and Candesartan Combination compared to monotherapy in patients with essential hypertension

Trial 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.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - 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).
  • - 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
    a) Gastrointestinal disease or surgery resulting in the potential for malabsorption
    b) Severe gastrointestinal tract narrowing; kock pouch (ileostomy after proctocolectomy)
    c) Cholestasis or biliary obstruction or history of pancreatic injury or clinical significant increase of lipase, amylase, or bilirubin.
    d) Liver disease or AST/ALT levels >3 x ULN
    e) 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.

Trial summary

Enrollment Goal
1381
Trial Dates
April 2011 - May 2012
Phase
Phase 2
Could I Receive a placebo
Yes
Products
Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Newmarket, L3Y 5G8, Canada
Completed
Addlestone, KT15 2BH, United Kingdom
Completed
Chesterfield, S40 4AA, United Kingdom
Completed
Trowbridge, BA14 8QA, United Kingdom
Completed
Bath, BA2 4JT, United Kingdom
Completed
Chippenham, SN15 2SB, United Kingdom
Completed
Leamington Spa, CV32 4RA, United Kingdom
Terminated
Fowey, PL23 1DT, United Kingdom
Completed
Penzance, TR18 4JH, United Kingdom
Completed
Penzance, TR19 7HX, United Kingdom
Completed
Blackpool, FY3 7EN, United Kingdom
Completed
Mt. Pleasant, 29464, United States
Completed
Dallas, 75230, United States
Completed
Jacksonville, 32216, United States
Completed
Cincinnati, 45224, United States
Completed
Mobile, 36617, United States
Completed
Atlanta, 30338, United States
Completed
Salisbury, 28144, United States
Completed
Charlotte, 28209, United States
Completed
Pavia, 27100, Italy
Completed
Sassari, 07100, Italy
Completed
Chieti, 66013, Italy
Terminated
Milano, 20132, Italy
Completed
Granada, 18012, Spain
Completed
Petrer, 03610, Spain
Completed
Peralada, 17491, Spain
Completed
Montreal, H4N 2W2, Canada
Completed
St. John's, A1A 3R5, Canada
Completed
St. John's, A1E 2E2, Canada
Completed
Sarnia, N7T 4X3, Canada
Completed
Corunna, N0N 1G0, Canada
Completed
Langley, V3A 4H9, Canada
Completed
Downsview, M3J 1N2, Canada
Completed
Seoul, 150-713, Korea, Republic Of
Completed
Goyang-si, 411-706, Korea, Republic Of
Completed
Seoul, 120-752, Korea, Republic Of
Completed
Seoul, 135-720, Korea, Republic Of
Completed
Busan, 602-793, Korea, Republic Of
Completed
Uijeongbu, 480-130, Korea, Republic Of
Terminated
Seoul, 156-707, Korea, Republic Of
Completed
Seoul, 156-755, Korea, Republic Of
Completed
Seoul, 158 710, Korea, Republic Of
Completed
Goyang-si, 410-773, Korea, Republic Of
Completed
Wonju-si, 220-701, Korea, Republic Of
Completed
Seoul, 152-703, Korea, Republic Of
Completed
Seoul, 150-950, Korea, Republic Of
Completed
Seoul, 110-744, Korea, Republic Of
Completed
Daejeon, 301-723, Korea, Republic Of
Completed
Goyang-si, 412-270, Korea, Republic Of
Completed
Kaunas, LT-50009, Lithuania
Completed
Vilnius, LT-08661, Lithuania
Completed
Kaunas, LT-50009, Lithuania
Completed
Kaunas, LT-49387, Lithuania
Completed
Alytus, LT-62381, Lithuania
Completed
Valencia, 46006, Spain
Completed
Hostalets de Balenyà, 08550, Spain
Completed
Stellenbosch, 7505, South Africa
Completed
Roodepoort, 1724, South Africa
Completed
Port Elizabeth, 6014, South Africa
Completed
Johannesburg, South Africa
Completed
Witbank, 1035, South Africa
Completed
Pisa, 56124, Italy
Terminated
Pavia, 27100, Italy
Terminated
Trieste, 34149, Italy
Completed
Bologna, 40138, Italy
Completed
Perugia, 06129, Italy
Completed
Mercato San Severino, 84085, Italy
Completed
Durban, 4037, South Africa
Terminated
São Paulo, 04025-011, Brazil
Terminated
Sao Paulo, 01244-030, Brazil
Terminated
Fortaleza, 60120-021, Brazil
Terminated
Goiania, 74605-050, Brazil
Terminated
Rio de Janeiro, 22271-100, Brazil
Terminated
Campinas, 13010-001, Brazil
Terminated
Campinas, 13060904, Brazil
Terminated
Brasília, 71265 009, Brazil
Completed
Bahía Blanca, 8000, Argentina
Completed
Zárate, B2800DGH, Argentina
Completed
Santa Fe, 3000, Argentina
Completed
Buenos Aires, C1425AWC, Argentina
Completed
Buenos Aires, C1280AEB, Argentina
Completed
Buenos Aires, C1425DES, Argentina
Completed
Buenos Aires, C1430AAQ, Argentina
Completed
Córdoba, X5002AOQ, Argentina
Completed
Rosario, 2000, Argentina
Completed
Córdoba, 5000, Argentina
Completed
Buenos Aires, C1440AAD, Argentina
Completed
Quilmes, Argentina
Completed
Rosario, 2000, Argentina
Completed
Kiev, 01 151, Ukraine
Completed
Kiev, 03680, Ukraine
Completed
Kiev, 01151, Ukraine
Completed
Zhytomyr, 10002, Ukraine
Completed
Kharkiv, 61176, Ukraine
Completed
Kiev, 03680, Ukraine
Terminated
St. Petersburg, 197022, Russia
Terminated
St. Petersburg, 197022, Russia
Terminated
Moscow, 117997, Russia
Terminated
St. Petersburg, 199106, Russia
Terminated
St. Petersburg, 199106, Russia
Terminated
Smolensk, 214019, Russia
Terminated
St. Petersburg, 197341, Russia
Terminated
Moscow, 125284, Russia
Terminated
Moscow, 115432, Russia
Terminated
St. Petersburg, 195112, Russia
Terminated
St Petersburg, 198013, Russia
Terminated
St. Petersburg, 196247, Russia
Terminated
Moscow, 119048, Russia
Completed
Moscow, 119415, Russia
Completed
St. Petersburg, 198205, Russia
Terminated
St. Petersburg, 195271, Russia
Completed
Deurne, 2100, Belgium
Completed
HAM, 3545, Belgium
Completed
Wetteren, 9230, Belgium
Completed
De Pinte, 9840, Belgium
Completed
Greenville, 29615, United States
Completed
Deerfield Beach, 33321, United States
Completed
Valparaiso, 46383, United States
Completed
Coral Gables, 33114-4192, United States
Completed
Raleigh, 27609, United States
Completed
Kiev, 03680, Ukraine
Completed
Kiev, 02660, Ukraine
Completed
Vinnitsa, 2108, Ukraine
Completed
Barcelona, 08036, Spain
Terminated
Santiago de Compostela, 15706, Spain
Completed
Benidorm, 03503, Spain
Terminated
Goyang-Si, 410-719, Korea, Republic Of
Terminated
Anyang-si, 431-070, Korea, Republic Of
Completed
Seoul, 133-792, Korea, Republic Of
Completed
Chungchungbuk-do, 361-711, Korea, Republic Of
Terminated
Oviedo, 33013, Spain
Completed
Huelva, 21003, Spain
Completed
Bath, BA11 2FH, United Kingdom
Completed
St Austell, PL26 7RL, United Kingdom
Completed
Kiev, 02 091, Ukraine
Completed
Dnipropetrovsk, 49060, Ukraine
Completed
Zaporizhzhya, 69118, Ukraine
Completed
Somerset West, 7130, South Africa
Terminated
Petoria, South Africa
Completed
Los Angeles, 90057, United States
Completed
Salt Lake City, 84121, United States
Completed
West Palm Beach, 33409, United States
Completed
Philadelphia, 19142, United States
Completed
Deerfield Beach, 33441, United States
Completed
Harrisburg, 28075, United States
Completed
Salt Lake City, 84109, United States
Completed
San Antonio, 78205, United States
Completed
Kenosha, 53142, United States
Completed
London, N5W 6A2, Canada
Completed
Toronto, M9V 4B4, Canada
Completed
Sarnia, N7T 4X3, Canada
Completed
Etobicoke, M8V 3X8, Canada
Completed
Toronto, M9W 4L6, Canada
Completed
Brampton, L6T 0G1, Canada
Completed
Strathroy, N7G 1Y7, Canada
Completed
London, N5Y 5K7, Canada
Terminated
Glasgow, G20 0XA, United Kingdom
Terminated
Glasgow, G20 7LR, United Kingdom
Completed
Bath, BA3 2UH, United Kingdom
Completed
Coventry, CV6 4DD, United Kingdom
Completed
Corrientes, 3400, Argentina
Completed
Rosario, 2000, Argentina
Completed
Buenos Aires, 1405, Argentina
Completed
Ft. Lauderdale, 33309, United States
Terminated
Bath, BA2 4BY, United Kingdom
Completed
Westbury, BA13 3JD, United Kingdom

Primary Outcome

  • The primary efficacy variable is the change from baseline in mean seated diastolic blood pressure (MSDBP) at Week 8
    date_rangeTime Frame:
    Baseline taken at Visit 1; primary outcome variable assesed at 8 weeks
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • Change in mean seated systolic blood pressure (MSSBP) at Week 8
    date_rangeTime Frame:
    8 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Control rate at Week 8
    date_rangeTime Frame:
    8 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Response rate at Week 8
    date_rangeTime Frame:
    8 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Peripheral Edema
    date_rangeTime Frame:
    8 weeks
    enhanced_encryption
    Safety Issue:
    Yes
  • Time to achieve first BP control
    date_rangeTime Frame:
    8 weeks
    enhanced_encryption
    Safety Issue:
    No

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
16