Study to Evaluate Efficacy of Micardis® (Telmisartan) and Valsartan in Patients With Mild-to-moderate Hypertension After Missing One Dose Using Ambulatory Blood Pressure Monitoring

Study Overview
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Brief Summary
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The primary aim of the trial is to compare telmisartan 80 mg to valsartan 160 mg in lowering diastolic blood pressure in patients who missed a dose of their medication, as measured by ABPM (change from baseline in mean DBP over 24 hours), and to compare telmisartan 80 mg to valsartan 160 mg in lowering DBP during the last six hours of the dosing interval at the end of a 6 to 8-week treatment period, as measured by ABPM (change from baseline)

Official Title
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A Prospective, Randomised, Double-blind, Double-dummy Trial to Compare the Efficacy of Micardis® (Telmisartan) (80 mg p.o. Once Daily) and Valsartan (160 mg p.o. Once Daily) in Patients With Mild-to-moderate Hypertension After Missing One Dose Using Ambulatory Blood Pressure Monitoring

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Valsartan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild-to-moderate hypertension defined as a mean seated diastolic blood pressure of ≥ 95 mmHg and ≤ 109 mmHg, measured by manual cuff sphygmomanometer, at Visit 2 24-hour mean DBP of ≥ 85 mmHg at Visit 3 as measured by ABPM Age 18 years or older Ability to stop any current antihypertensive therapy without risk to the patient (investigator's discretion) Patient's written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Exclusion Criteria: Pre-menopausal women (last menstruation ≤ 1 year prior to start of run-in period) who are not surgically sterile, are nursing, are of child-bearing potential and are NOT practising acceptable methods of birth control, or do NOT plan to continue practising an acceptable method throughout the study. Acceptable methods of birth control include oral, implantable or injectable contraceptives and Intra Uterine Devices (IUD) Known or suspected secondary hypertension Mean sitting SBP ≥180 mmHg or mean sitting DBP ≥110 mmHg during any visit of the placebo run-in period Hepatic and/or renal dysfunction as defined by the following laboratory parameters: Serum Glutamate-Pyruvate-Transaminase (Alanine Aminotransferase) (SGPT (ALT)) or Serum Glutamate-Oxaloacetate-Transaminase (Aspartate Aminotransferase) (SGOT (AST)) > than 2 times the upper limit of normal range, Serum creatinine > 2.3 mg/dL (or > 203 μmol/l) Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients postrenal transplant or with only one kidney Clinically relevant sodium depletion, hypokalaemia or hyperkalaemia Uncorrected volume depletion Primary aldosteronism Hereditary fructose intolerance Biliary obstructive disorders Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists History of drug or alcohol dependency within six months prior to start of run-in period Concomitant administration of any medications known to affect blood pressure, except medication allowed by the protocol Any investigational therapy within one month of signing the informed consent form Congestive heart failure (New York Heart Association (NYHA) functional class Congestive Heart Failure (CHF III-IV)) Unstable angina within the past three months prior to start of run-in period Stroke within the past six months prior to start of run-in period Myocardial infarction or cardiac surgery within the past three months prior to start of run-in period Percutaneous Transluminal Coronary Angioplasty (PTCA) within the past three months prior to start of run-in period Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the investigator Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve Patients with insulin-dependent diabetes mellitus whose diabetes has not been stable and controlled for at least the past three months as defined by an HbA1C ≥ 10% Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 Ante Meridiem (AM) Known hypersensitivity to any component of the formulations Any clinical condition which, in the opinion of the investigator would not allow safe completion of the protocol and safe administration of trial medication Inability to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan<br>low dose for two weeks, then up titration to high dose, once daily | Drug: Telmisartan<br> <br> Drug: Placebo<br> <br> |
| Active Comparator: Valsartan<br>low dose for two weeks, then up titration to high dose, once daily | Drug: Valsartan<br> <br> Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24 hour mean Diastolic blood pressure (DBP) after a missed dose | measured by ambulatory blood pressure monitoring (ABPM) | Baseline, Day 41, Day 55 | 
| Change in mean DBP during the last 6 hours of the 24 hour dosing interval |  | up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour mean systolic blood pressure (SBP) after a missed dose |  | Baseline, Day 41, Day 55 | 
| Change in mean SBP during the last 6 hours of the 24-hour dosing interval |  | up to 8 weeks | 
| Change in pulse pressure (PP) |  | up to 8 weeks | 
| Change in 24-hour mean DBP after an active dose of study medication |  | up to 8 weeks | 
| Change in 24-hour mean SBP after an active dose of study medication |  | up to 8 weeks | 
| Change in mean seated trough SBP/DBP/PP in- clinic manual cuff sphygmomanometer after a missed dose |  | up to 8 weeks | 
| Change in the mean seated trough SBP/DBP/PP in- clinic manual cuff sphygmomanometer after an active dose of study medication |  | up to 8 weeks | 
| Responder rate measured by ABPM after a missed dose of study medication | ABPM DBP control (24-hour mean DBP < 80 mmHg), ABPM DBP response (24-hour mean DBP < 80 mmHg and/or reduction from baseline ≥ 10 mmHg), ABPM SBP response (24-hour mean SBP < 130 mmHg and/or reduction from baseline ≥ 10 mmHg) | Baseline, Day 41, Day 55 | 
| Responder rate measured by ABPM after an active dose of study medication | ABPM DBP control (24-hour mean DBP < 80 mmHg), ABPM DBP response (24-hour mean DBP < 80 mmHg and/or reduction from baseline ≥ 10 mmHg), ABPM SBP response (24-hour mean SBP < 130 mmHg and/or reduction from baseline ≥ 10 mmHg) | up to 8 weeks | 
| Responder rate in- clinic manual trough cuff measurements after a missed dose of study medication | DBP control (DBP < 90 mmHg), DBP response (DBP < 90 mmHg and/or fall of ≥ 10 mmHg), SBP response (SBP < 140 mmHg and/or fall of ≥ 10 mmHg), BP normal (SBP < 130 mmHg and DBP < 85 mmHg), BP normal / high normal (SBP < 140 mmHg and DBP < 90 mmHg). | Baseline, Day 41, Day 55 | 
| Responder rate in- clinic manual trough cuff measurements after an active dose of study medication | DBP control (DBP < 90 mmHg), DBP response (DBP < 90 mmHg and/or fall of ≥ 10 mmHg), SBP response (SBP < 140 mmHg and/or fall of ≥ 10 mmHg), BP normal (SBP < 130 mmHg and DBP < 85 mmHg), BP normal / high normal (SBP < 140 mmHg and DBP < 90 mmHg). | up to 8 weeks | 
| Number of patients with adverse events |  | up to 8 weeks | 
| Change in 24-hour Pulse Pressure (PP) after a missed dose |  | Baseline, Day 41, Day 55 |