Telmisartan Fixed Dose Combination vs Amlodipine in Hypertensive Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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To demonstrate that the fixed dose combination of telmisartan and amlodipine is more effective in lowering blood pressure.

Official Title
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An 8-week Randomised, Double-blind Study to Compare the Fixed-dose Combination of Telmisartan 80 + Amlodipine 10mg Versus Amlodipine 10 mg Monotherapy as First Line Therapy in Type 2 Diabetes Patients With Hypertension.

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Telmisartan 80
* Drug: Amlodipine 10
* Drug: Amlodipine 10


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Hypertension defined as a mean in-clinic seated cuff Systolic Blood Pressure >150 mmHg at Visit 3 (Randomisation visit) Diagnosis of Type 2 diabetes mellitus =18 years of age at the date of signing the informed consent Ability to stop current antihypertensive therapy without unacceptable risk to the patient (investigator's discretion) Ability to provide written informed consent Exclusion criteria: Pre-menopausal women (last menstruation <=1 year prior to start of run-in period) who: are not surgically sterile; and/or are nursing or pregnant, or are of child-bearing potential and are NOT practicing acceptable means of birth control or do NOT plan to continue practising an acceptable method throughout the study. The only acceptable methods of birth control are: Intrauterine device (IUD); Oral contraceptives (started at least three months prior to start of run-in period) Implantable or injectable contraceptives and Estrogen patch Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m. Known or suspected secondary hypertension (e.g., renal artery stenosis, phaeochromocytoma) Mean seated Systolic Blood Pressure (SBP) =180 mm Hg and/or mean seated Diastolic Blood Pressure (DBP) =110 mm Hg during any visit of the screening and placebo run-in periods Patients with Type 1 diabetes mellitus Renal dysfunction as defined by the following laboratory parameters: Serum creatinine >3.0 mg/dL (or >265 µmol /L) or known creatinine clearance <30 mL/min or clinical markers of severe renal impairment Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant patients or patients with only one kidney Clinically relevant hypokalaemia or hyperkalaemia Uncorrected sodium or volume depletion Primary aldosteronism Hereditary fructose intolerance Biliary obstructive disorders (e.g., cholestatis) or hepatic insufficiency Congestive heart failure New York Heart Academy (NYHA) functional class CHF III-IV (Refer to Appendix 10.3) Contraindication to a placebo run-in period (e.g., stroke with-in the past six months, myocardial infarction, cardiac surgery, percutaneous transluminal coronary angioplasty, unstable angina or coronary artery bypass graft within the past three months prior to start of run-in period) Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the Investigator Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve Patients whose diabetes has not been stable and controlled for at least the past three months as defined by an HbA1C >10% Patients who have previously experienced symptoms characteristic of angioedema during treatment with Angiotensin Converting Enzyme (ACE) inhibitors or angiotensin-II receptor antagonists History of drug or alcohol dependency within six months prior to signing the informed consent form Concomitant administration of any medications known to affect blood pressure, except medications allowed by the protocol Any investigational drug therapy within one month of signing the informed consent Known hypersensitivity to any component of the study drugs (telmisartan, amlodipine, or placebo) History of non-compliance or inability to comply with prescribed medications or protocol procedures Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of telmisartan and amlodipine

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 80 / Amlodipine 10<br>Telmisartan 80 / Amlodipine 5 for two weeks, then forced titration to Telmisartan 80 / Amlodipine 10 Fixed Dose Combination | Drug: Telmisartan 80<br>* Telmisartan 80 mg<br>Drug: Amlodipine 10<br>* Amlodipine 5 for two weeks, then forced titration to Amlodipine 10<br>|
| Active Comparator: Amlodipine 10<br>Amlodipine 5 for two weeks, then forced titration to Amlodipine 10 | Drug: Amlodipine 10<br>* Amlodipine 5 for two weeks, then forced titration to Amlodipine 10<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Seated Systolic Blood Pressure to Week 8 | Trough blood pressure measurements were the measurements observed at the end of the dosing interval just prior to the next dose of medication. | Baseline, week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Seated Systolic Blood Pressure to Week 6 | Trough blood pressure measurements were the measurements observed at the end of the dosing interval just prior to the next dose of medication. | Baseline, week 6 | 
| Change From Baseline in Trough Seated Systolic Blood Pressure to Week 4 | Trough blood pressure measurements were the measurements observed at the end of the dosing interval just prior to the next dose of medication. | Baseline, week 4 | 
| Change From Baseline in Trough Seated Systolic Blood Pressure to Week 2 | Trough blood pressure measurements were the measurements observed at the end of the dosing interval just prior to the next dose of medication. | Baseline, week 2 | 
| Change From Baseline in Trough Seated Systolic Blood Pressure to Week 1 | Trough blood pressure measurements were the measurements observed at the end of the dosing interval just prior to the next dose of medication. | Baseline, week 1 | 
| Blood Pressure (BP) Control (SBP<140 mmHg, DBP<90 mmHg) at Eight Weeks | Mean seated SBP<140 mmHg and mean seated DBP<90 mmHg | Baseline, week 8 | 
| BP Control (SBP<140 mmHg, DBP<90 mmHg) at Six Weeks | Mean seated SBP<140 mmHg and mean seated DBP<90 mmHg | Baseline, week 6 | 
| BP Control (SBP<140 mmHg, DBP<90 mmHg) at Four Weeks | Mean seated SBP<140 mmHg and mean seated DBP<90 mmHg | Baseline, week 4 | 
| BP Control (SBP<140 mmHg, DBP<90 mmHg) at Two Weeks | Mean seated SBP<140 mmHg and mean seated DBP<90 mmHg | Baseline, week 2 | 
| BP Control (SBP<140 mmHg, DBP<90 mmHg) at One Week | Mean seated SBP<140 mmHg and mean seated DBP<90 mmHg | Baseline, week 1 | 
| BP Control (SBP<130 mmHg, DBP<80 mmHg) at Eight Weeks | Mean seated SBP<130 mmHg and mean seated DBP<80 mmHg | Baseline, week 8 | 
| BP Control (SBP<130 mmHg, DBP<80 mmHg) at Six Weeks | Mean seated SBP<130 mmHg and mean seated DBP<80 mmHg | Baseline, week 6 | 
| BP Control (SBP<130 mmHg, DBP<80 mmHg) at Four Weeks | Mean seated SBP<130 mmHg and mean seated DBP<80 mmHg | Baseline, week 4 | 
| BP Control (SBP<130 mmHg, DBP<80 mmHg) at Two Weeks | Mean seated SBP<130 mmHg and mean seated DBP<80 mmHg | Baseline, week 2 | 
| BP Control (SBP<130 mmHg, DBP<80 mmHg) at One Week | Mean seated SBP<130 mmHg and mean seated DBP<80 mmHg | Baseline, week 1 | 
| Systolic Blood Pressure (SBP) Control 140 at Eight Weeks | Mean seated SBP < 140 mmHg | Baseline, week 8 | 
| SBP Control 140 at Six Weeks | Mean seated SBP < 140 mmHg | Baseline, week 6 | 
| SBP Control 140 at Four Weeks | Mean seated SBP < 140 mmHg | Baseline, week 4 | 
| SBP Control 140 at Two Weeks | Mean seated SBP < 140 mmHg | Baseline, week 2 | 
| SBP Control 140 at One Week | Mean seated SBP < 140 mmHg | Baseline, week 1 | 
| SBP Control 130 at Eight Weeks | Mean seated SBP < 130 mmHg | Baseline, week 8 | 
| SBP Control 130 at Six Weeks | Mean seated SBP < 130 mmHg | Baseline, week 6 | 
| SBP Control 130 at Four Weeks | Mean seated SBP < 130 mmHg | Baseline, week 4 | 
| SBP Control 130 at Two Weeks | Mean seated SBP < 130 mmHg | Baseline, week 2 | 
| SBP Control 130 at One Week | Mean seated SBP < 130 mmHg | Baseline, week 1 | 
| SBP Response 140 at Eight Weeks | SBP < 140 mmHg or a reduction >=10 mmHg | Baseline, week 8 | 
| SBP Response 140 at Six Weeks | SBP <140 mmHg or a reduction >=10 mmHg | Baseline, week 6 | 
| SBP Response 140 at Four Weeks | SBP <140 mmHg or a reduction >=10 mmHg | Baseline, week 4 | 
| SBP Response 140 at Two Weeks | SBP <140 mmHg or a reduction >=10 mmHg | Baseline, week 2 | 
| SBP Response 140 at One Week | SBP <140 mmHg or a reduction >=10 mmHg | Baseline, week 1 | 
| SBP Response 130 at Eight Weeks | SBP <130 mmHg or a reduction >=10 mmHg | Baseline, week 8 | 
| SBP Response 130 at Six Weeks | SBP <130 mmHg or a reduction >=10 mmHg | Baseline, week 6 | 
| SBP Response 130 at Four Weeks | SBP <130 mmHg or a reduction >=10 mmHg | Baseline, week 4 | 
| SBP Response 130 at Two Weeks | SBP <130 mmHg or a reduction >=10 mmHg | Baseline, week 2 | 
| SBP Response 130 at One Week | SBP <130 mmHg or a reduction >=10 mmHg | Baseline, week 1 | 
| DBP Response at Eight Weeks | Mean seated DBP<80 mmHg or a reduction of <=10 mmHg | Week 8 | 
| DBP Response at Six Weeks | Mean seated DBP<80 mmHg or a reduction of <=10 mmHg | week 6 | 
| DBP Response at Week Four | Mean seated DBP <80 mmHg or a reduction of >=10 mmHg | Week 4 | 
| DBP Response at Week Two | Mean seated DBP <80 mmHg or a reduction of >=10 mmHg | Week 2 | 
| DBP Response at Week One | Mean seated DBP <80 mmHg or a reduction of >=10 mmHg | Week 1 | 
| Change From Baseline in Urine Albumin:Creatinine Ratio (UACR) | Change from baseline in UACR (measured in spot urine) after eight weeks of treatment | 8 weeks |