Hypertension
Conditions
Brief summary
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)
Interventions
DRUGTelmisartan
DRUGValsartan
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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 2. 24-hour mean DBP of ≥ 85 mmHg at Visit 3 as measured by ABPM 3. Age 18 years or older 4. Ability to stop any current antihypertensive therapy without risk to the patient (investigator's discretion) 5. Patient's written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
Exclusion criteria
1. Pre-menopausal women (last menstruation ≤ 1 year prior to start of run-in period) who 1. are not surgically sterile, 2. are nursing, 3. 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) 2. Known or suspected secondary hypertension 3. Mean sitting SBP ≥180 mmHg or mean sitting DBP ≥110 mmHg during any visit of the placebo run-in period 4. Hepatic and/or renal dysfunction as defined by the following laboratory parameters: 1. 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, 2. Serum creatinine \> 2.3 mg/dL (or \> 203 μmol/l) 5. Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients postrenal transplant or with only one kidney 6. Clinically relevant sodium depletion, hypokalaemia or hyperkalaemia 7. Uncorrected volume depletion 8. Primary aldosteronism 9. Hereditary fructose intolerance 10. Biliary obstructive disorders 11. Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists 12. History of drug or alcohol dependency within six months prior to start of run-in period 13. Concomitant administration of any medications known to affect blood pressure, except medication allowed by the protocol 14. Any investigational therapy within one month of signing the informed consent form 15. Congestive heart failure (New York Heart Association (NYHA) functional class Congestive Heart Failure (CHF III-IV)) 16. Unstable angina within the past three months prior to start of run-in period 17. Stroke within the past six months prior to start of run-in period 18. Myocardial infarction or cardiac surgery within the past three months prior to start of run-in period 19. Percutaneous Transluminal Coronary Angioplasty (PTCA) within the past three months prior to start of run-in period 20. Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the investigator 21. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve 22. 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% 23. Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 Ante Meridiem (AM) 24. Known hypersensitivity to any component of the formulations 25. Any clinical condition which, in the opinion of the investigator would not allow safe completion of the protocol and safe administration of trial medication 26. Inability to comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24 hour mean Diastolic blood pressure (DBP) after a missed dose | Baseline, Day 41, Day 55 | measured by ambulatory blood pressure monitoring (ABPM) |
| Change in mean DBP during the last 6 hours of the 24 hour dosing interval | up to 8 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 systolic blood pressure (SBP) after a missed dose | Baseline, Day 41, Day 55 | — |
| 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 | — |
| Change in 24-hour mean SBP after an active dose of study medication | up to 8 weeks | — |
| Responder rate measured by ABPM after an active dose of study medication | up to 8 weeks | * 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) |
| Responder rate in- clinic manual trough cuff measurements after a missed dose of study medication | Baseline, Day 41, Day 55 | * 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). |
| Responder rate in- clinic manual trough cuff measurements after an active dose of study medication | up to 8 weeks | * 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). |
| 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 | — |
| Responder rate measured by ABPM after a missed dose of study medication | Baseline, Day 41, Day 55 | * 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) |
| Change in mean SBP during the last 6 hours of the 24-hour dosing interval | up to 8 weeks | — |
Outcome results
None listed