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

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

Sponsors

Lead Sponsor: Bayer

Source Bayer
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.

Overall Status Completed
Start Date 2011-04-01
Completion Date 2012-05-01
Primary Completion Date 2012-05-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
The primary efficacy variable is the change from baseline in mean seated diastolic blood pressure (MSDBP) at Week 8 Baseline taken at Visit 1; primary outcome variable assesed at 8 weeks
Secondary Outcome
Measure Time Frame
Change in mean seated systolic blood pressure (MSSBP) at Week 8 8 weeks
Control rate at Week 8 8 weeks
Response rate at Week 8 8 weeks
Peripheral Edema 8 weeks
Time to achieve first BP control 8 weeks
Enrollment 1381
Condition
Intervention

Intervention Type: Drug

Intervention Name: Candesartan cilexetil (Atacand), 4 mg

Description: 4 mg of candesartan as capsule

Intervention Type: Drug

Intervention Name: Candesartan cilexetil (Atacand), 8 mg

Description: 8 mg candesartan as capsule

Intervention Type: Drug

Intervention Name: Nifedipine GITS (Adalat, BAYA1040), 20 mg

Description: 20 mg nifedipine as tablet

Intervention Type: Drug

Intervention Name: Nifedipine GITS (Adalat, BAYA1040), 30 mg

Description: 30 mg nifedipine as tablet

Intervention Type: Drug

Intervention Name: Nifedipine GITS (Adalat, BAYA1040), 60 mg

Description: 60 mg nifedipine as tablet

Intervention Type: Drug

Intervention Name: Placebo

Description: 3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses

Intervention Type: Drug

Intervention Name: Candesartan cilexetil (Atacand), 16 mg

Description: 16 mg of candesartan as capsule

Intervention Type: Drug

Intervention Name: Candesartan cilexetil (Atacand), 32 mg

Description: 32 mg of candesartan as capsule

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 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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

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

Argentina

Belgium

Brazil

Canada

Italy

Korea, Republic of

Lithuania

Russian Federation

South Africa

Spain

Ukraine

United Kingdom

United States

Verification Date

2017-04-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 16
Arm Group

Label: Nifedipine GITS 20 mg

Type: Experimental

Description: Subjects received 20 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule

Label: Nifedipine GITS 30 mg

Type: Experimental

Description: Subjects received 30 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule

Label: Nifedipine GITS 60 mg

Type: Experimental

Description: Subjects received 60 mg of nifedipine GITS (single tablet) monotherapy once daily for 8 weeks along with 2 placebo tablets and 1 placebo capsule

Label: Candesartan cilexetil 4 mg

Type: Experimental

Description: Subjects received 4 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets

Label: Candesartan cilexetil 8 mg

Type: Experimental

Description: Subjects received 8 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets

Label: Candesartan cilexetil 16 mg

Type: Experimental

Description: Subjects received 16 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets

Label: Candesartan cilexetil 32 mg

Type: Experimental

Description: Subjects received 32 mg of candesartan cilexetil (single capsule) monotherapy once daily for 8 weeks along with 3 placebo tablets

Label: Nifedipine/candesartan 20/4 mg

Type: Experimental

Description: 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

Label: Nifedipine/candesartan 20/8 mg

Type: Experimental

Description: 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

Label: Nifedipine/candesartan 20/16 mg

Type: Experimental

Description: 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

Label: Nifedipine/candesartan 30/8 mg

Type: Experimental

Description: 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

Label: Nifedipine/candesartan 30/16 mg

Type: Experimental

Description: 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

Label: Nifedipine/candesartan 30/32 mg

Type: Experimental

Description: 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

Label: Nifedipine/candesartan 60/16 mg

Type: Experimental

Description: 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

Label: Nifedipine/candesartan 60/32 mg

Type: Experimental

Description: 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

Label: Placebo

Type: Placebo Comparator

Description: Subjects received placebo (3 tablets and 1 capsule) once daily for 8 weeks

Acronym DISTINCT
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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