Combination of Telmisartan and Simvastatin in the Treatment of Hypertension and Hypercholesterolemia

Reduced Factorial Design, Randomized, Double Blind Trial Comparing Combinations of Telmisartan 20 or 80 mg and Simvastatin 20 or 40 mg With Single Component Therapies in the Treatment of Hypertension and Dyslipidemia

This study will investigate two registered drugs, one for the treatment of high blood pressure and one for the treatment of elevated cholesterol. High blood pressure (hypertension) is a common medical condition affecting millions of people worldwide. A wide variety of effective drug treatments is available to reduce blood pressure. Elevated cholesterol (hypercholesterolemia) is a common medical condition affecting people worldwide. A wide variety of effective drug treatments is available to reduce cholesterol levels.

Hypertension and hypercholesterolemia often occur together. They are both important risk factors for the development of heart and vessel diseases (e.g. heart attack or stroke). Current guidelines advise treatment of high blood pressure and elevated cholesterol to reduce the risk of cardiovascular diseases. This study will test the simultaneous use of a drug to reduce blood pressure and a drug to reduce elevated cholesterol. Both drugs are registered and are effective. The drug for treatment of high blood pressure is telmisartan Micardis). The drug for treatment of elevated cholesterol is simvastatin (Zocor). Since hypertension and hypercholesterolemia frequently occur together, the purpose of this study is to investigate whether both drugs can be used simultaneously. A low dose and a high dose of these drugs will be used. It will be investigated whether each of the drugs is still as effective when given together, at the same time of day, with the other drug.

Study Overview

• Status: Completed
• Conditions: Hypertension; Dyslipidemias
• Intervention / Treatment: Drug: simvastatin; Drug: telmisartan

• Study Type: Interventional
• Enrollment: 1695
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czech Republic
  • Benatky nad Jizerou, Czech Republic, 294 71
    • Boehringer Ingelheim Investigational Site
  • Brno, Czech Republic, 65691
    • Boehringer Ingelheim Investigational Site
  • Mlada Boleslav, Czech Republic, 293 01
    • Boehringer Ingelheim Investigational Site
  • Plzen, Czech Republic, 301 00
    • Boehringer Ingelheim Investigational Site
  • Praha 5, Czech Republic, 158 00
    • Boehringer Ingelheim Investigational Site
  • Pribram, Czech Republic, 261 01
    • Boehringer Ingelheim Investigational Site
  • Unicov, Czech Republic, 783 91
    • Boehringer Ingelheim Investigational Site
  • Usti nad Orlici, Czech Republic, 562 18
    • Boehringer Ingelheim Investigational Site
• France
  • Angers, France, 49000
    • ALTI
  • Angers, France, 49000
    • Boehringer Ingelheim Investigational Site
  • Sidi Daoud Tunis, France, 2046
    • Boehringer Ingelheim Investigational Site
  • Tunis, France, 1089
    • Boehringer Ingelheim Investigational Site
• Germany
  • Haag, Germany, 83527
    • Boehringer Ingelheim Investigational Site
  • Mainz, Germany, 55116
    • Boehringer Ingelheim Investigational Site
  • Neuburg a. d. Donau, Germany, 86633
    • Boehringer Ingelheim Investigational Site
  • Nurnberg, Germany, 90402
    • Boehringer Ingelheim Investigational Site
  • Rednitzhembach, Germany, 91126
    • Boehringer Ingelheim Investigational Site
  • Unterschneidheim, Germany, 73485
    • Boehringer Ingelheim Investigational Site
  • Westerkappeln, Germany, 49492
    • Boehringer Ingelheim Investigational Site
  • Wiesbaden, Germany, 65191
    • Boehringer Ingelheim Investigational Site
  • Wurzburg, Germany, 97072
    • Boehringer Ingelheim Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Boehringer Ingelheim Investigational Site
• Korea, Republic of
  • Kwangju, Korea, Republic of, 501757
    • Chonnam National University Hospital
  • Kyunggi-do, Korea, Republic of, 431070
    • Hallym University Sacred Heart Hospital
  • Seoul, Korea, Republic of, 110774
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120752
    • Severance Hospital
  • Seoul, Korea, Republic of, 136705
    • Korea University Medical Center
  • Seoul, Korea, Republic of, 150713
    • St. Mary Hospital
• Netherlands
  • Almere, Netherlands, 1311RL
    • Boehringer Ingelheim Investigational Site
  • Beek en Donk, Netherlands, 5741 CG
    • Boehringer Ingelheim Investigational Site
  • Breda, Netherlands, 4811 VL
    • Andromed Breda
  • Den Helder, Netherlands, 1782 GZ
    • Gemini Ziekenhuis
  • Eindhoven, Netherlands, 5611 NJ
    • Andromed Eindhoven
  • Ewijk, Netherlands, 6644 CL
    • Boehringer Ingelheim Investigational Site
  • Groningen, Netherlands, 9711 SG
    • Andromed Noord
  • Leiden, Netherlands, 2311 GZ
    • Andromed Leiden
  • Nijmegen, Netherlands, 6533 HL
    • Andromed Nijmegen
  • Oude Pekela, Netherlands, 9665 BJ
    • Boehringer Ingelheim Investigational Site
  • Rotterdam, Netherlands, 3021 HC
    • Andromed Rotterdam
  • Utrecht, Netherlands, 3584 CJ
    • Julius Center for Patient oriented Research
  • Velp, Netherlands, 6883 ES
    • Andromed Oost
  • Wildervank, Netherlands, 9648 BE
    • Boehringer Ingelheim Investigational Site
  • Zoetermeer, Netherlands, 2724 EK
    • Andromed Zoetermeer
• Russian Federation
  • Moscow, Russian Federation, 101990
    • Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation, 117036
    • Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation, 119992
    • Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation, 121356
    • Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation, 121552
    • Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation, 127018
    • Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation, 129010
    • Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation, 195257
    • Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation, 198013
    • Boehringer Ingelheim Investigational Site
• Slovakia
  • Bratislava, Slovakia, 82606
    • Boehringer Ingelheim Investigational Site
  • Kosice, Slovakia, 040 01
    • Boehringer Ingelheim Investigational Site
  • Kralovsky Chmlec, Slovakia, 077 01
    • Boehringer Ingelheim Investigational Site
  • Liptovsky Hradok, Slovakia, 033 01
    • Boehringer Ingelheim Investigational Site
  • Nitra, Slovakia, 950 01
    • Boehringer Ingelheim Investigational Site
  • Povazska Bystrica, Slovakia, 017 01
    • Boehringer Ingelheim Investigational Site
  • Presov, Slovakia, 081 81
    • Boehringer Ingelheim Investigational Site
  • Trencin, Slovakia, 911 05
    • Boehringer Ingelheim Investigational Site
  • Vrable, Slovakia, 952 01
    • Boehringer Ingelheim Investigational Site
• South Africa
  • Boksburg, South Africa, 1461
    • Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa, 7405
    • Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa, 7925
    • Boehringer Ingelheim Investigational Site
  • Durban, South Africa, 4091
    • Boehringer Ingelheim Investigational Site
  • Johannesburg, South Africa, 2033
    • Boehringer Ingelheim Investigational Site
  • Krugersdorp, South Africa, 1739
    • Boehringer Ingelheim Investigational Site
  • Midrand, South Africa, 1685
    • Boehringer Ingelheim Investigational Site
• Sweden
  • Goteborg, Sweden, 416 85
    • Medicinkliniken
  • Lule?, Sweden, 971 80
    • Medicinkliniken
  • Lule?, Sweden, S-971 31
    • Boehringer Ingelheim Investigational Site
  • Malmo, Sweden, 205 02
    • Endokrinologkliniken
  • Rattvik, Sweden, 795 33
    • Boehringer Ingelheim Investigational Site
  • Stockholm, Sweden, 182 88
    • Medicinkliniken
  • Uppsala, Sweden, S-752 23
    • Boehringer Ingelheim Investigational Site
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 104
    • Mackay Memorial Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital
• Ukraine
  • Dnepropetrovsk, Ukraine, 49006
    • Boehringer Ingelheim Investigational Site
  • Dnepropetrovsk, Ukraine, 49023
    • Boehringer Ingelheim Investigational Site
  • Ivano-Frankovsk, Ukraine, 76000
    • Boehringer Ingelheim Investigational Site
  • Kharkov, Ukraine, 61018
    • Boehringer Ingelheim Investigational Site
  • Kharkov, Ukraine, 61037
    • Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine, 02175
    • Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine, 03151
    • Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine, 03680
    • Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine, 04114
    • Boehringer Ingelheim Investigational Site
  • Lutsk, Ukraine, 43024
    • Boehringer Ingelheim Investigational Site
  • Lvov, Ukraine, 73013
    • Boehringer Ingelheim Investigational Site
  • Lvov, Ukraine, 79015
    • Boehringer Ingelheim Investigational Site
  • Zaporozhye, Ukraine, 69035
    • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to provide written informed consent
• Age 18 years or older
• Hypertension as defined by a mean seated cuff DBP of >=95 - 109 mmHg
• Hypercholesterolemia as defined by a fasting LDL-C level at visit 2 according to

• CV risk shown in table below:

  • CV Risk Group:

    1. Group I Hypertension and Hypercholesterolemia only
    2. Group II Hypertension and Hypercholesterolemia plus > 1 risk factors
    3. Group III Hypertension and Hypercholesterolemia plus CHD and/or diabetes mellitus and/or other athero-sclerotic disease
• Fasting LDL-C group I and II: 100-250 mg/dL (2.6-6.5 mmol/L)
• Fasting LDL-C group III: 100-160 mg/dL (2.6-4.1 mmol/L)
• Risk factors: >= 45 yrs if male, >= 55 years if female, family history of CHD, current smoker, HDL-C < 40 mg/dL

Exclusion Criteria:

• pre-menopausal women who are not surgically sterile or are nursing or pregnant or are of child-bearing potential and are not practicing acceptable means of birth control
• inability to stop current antihypertensive and/or cholesterol-lowering therapies
• contraindication to a washout/placebo treatment
• clinically relevant cardiac arrhythmias
• hypertrophic obstructive cardiomyopathy, hemodynamically relevant stenosis of the aortic or mitral valve
• mean sitting SBP >=180 mmHg or mean sitting DBP >=110 mmHg at two consecutive visits
• known or suspected secondary hypertension
• known or suspected secondary hyperlipidemia of any etiology
• diabetes that has not been stable and controlled for the previous three months
• severe renal dysfunction
• bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant or one kidney
• biliary obstructive disorders, hepatic insufficiency, including past or current liver disease
• clinically relevant hypokalaemia or hyperkalaemia
• uncorrected volume depletion
• uncorrected sodium depletion
• any history of myopathy or rhabdomyolysis during the past treatment with HMG Co-A reductase inhibitors
• concurrent use of large quantities of grapefruit juice
• known hypersensitivity or intolerance to HMG Co-A reductase inhibitors and/or angiotensin receptor blockers, hereditary fructose intolerance
• planned significant diet and/or lifestyle (including exercise) changes during the treatment phase of the trial
• history of drug or alcohol dependency
• any investigational drug therapy within one month of providing informed consent
• any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the trial medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in 24-hour ambulatory blood pressure measurement (ABPM) measured mean diastolic blood pressure (DBP)	8 weeks
Change in 24-hour ambulatory blood pressure measurement (ABPM) measured mean low density lipoprotein (LDL)	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in the 24-hour ABPM (Ambulatory Blood Pressure Monitoring) measured mean SBP	after 8 weeks
Changes in Trough-to-peak ratios of SBP and DBP, taken from ABPM	after 8 weeks
Changes in Seated morning DBP and SBP	after 8 weeks
Response rate to blood pressure treatment	after 8 weeks
Response rate to lipid lowering treatment	after 8 weeks
Change in Total cholesterol	after 8 weeks
Change in HDL-cholesterol	after 8 weeks
Change in triglycerides	after 8 weeks
Change in Apolipoprotein B	after 8 weeks
Change in free fatty acids	after 8 weeks
Change in Adiponectin	after 8 weeks
Change in HOMA-index	after 8 weeks
Change in haemoglobin A1C	after 8 weeks
Changes in high sensitive c-reactive protein	after 8 weeks
Changes in microalbuminuria	after 8 weeks
Adverse events	up to 15 weeks
Changes in clinical laboratory parameter	up to 15 weeks
Assessment of pulse rate	up to 15 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): August 1, 2007
• Study Completion: August 1, 2007

Study Registration Dates

• First Submitted: April 19, 2006
• First Submitted That Met QC Criteria: April 19, 2006
• First Posted (Estimate): April 20, 2006

Study Record Updates

• Last Update Posted (Estimate): November 1, 2013
• Last Update Submitted That Met QC Criteria: October 31, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hypertension; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Simvastatin; Telmisartan
• Other Study ID Numbers: 1228.1; EudraCT No.: 2005-002851-41