8-week Randomized, Open-label Study to Evaluate Food Effect on Efficacy and Safety of Oral Aliskiren 300 mg in Patients With Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of food on aliskiren's efficacy, pharmacokinetics and safety following an oral dose of 300 mg, given once daily under light meal versus fasted conditions.

Official Title
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An 8-week Randomized, Open-label, Multi-center Study to Evaluate the Efficacy and Safety of Oral Aliskiren 300 mg Once Daily Under Light Meal Versus Fasted Condition in Patients With Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy). Patients with an office BP ≥ 140/90 mmHg and < 180/110mmHg at the randomization visit and the preceding visit Patients must have an absolute difference of ≤ 10 mmHg in both their msSBP and their msDBP between the randomization visit and the preceding visit Exclusion Criteria: Malignant hypertension or severe hypertension (grade 3 of WHO classification; msSBP ≥180 mmHg or msDBP ≥110 mmHg) History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, drug-induced hypertension, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease (PKD). Type 1 or Type 2 diabetes mellitus with a fasting glycosylated hemoglobin (HbA1c) > 8% Evidence of renal impairment as determined by one of the following: serum creatinine >1.5 x ULN or eGFR < 30 ml/min/1.73m2 at Visit 1, a history of dialysis, or a history of nephrotic syndrome Other protocol-defined inclusion/exclusion criteria may apply. -

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren: Fed<br>Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast | Drug: Aliskiren<br>* Aliskiren 300 mg once daily<br>* Other names: Tekturna, rasilez;|
| Experimental: Aliskiren: Fasting<br>Aliskiren 300 mg once daily taken after after an overnight fast | Drug: Aliskiren<br>* Aliskiren 300 mg once daily<br>* Other names: Tekturna, rasilez;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Systolic Blood Pressure (maSBP) | 24 hour ambulatory blood pressure measurement (ABPM) were taken twice, at baseline and at the end of 8 weeks. An Ambulatory Blood Pressure Monitoring device (ABPM) was attached to the non-dominant arm. The mean change of 24 hours maSBP from baseline to week 8 was estimated using an Analysis of Covariance (ANCOVA) model by using treatment, region as factors, and baseline as covariate. | Baseline, week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) in Fasted vs. Fed | Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis. | Week 4 (0, 0.5, 1, 1.5, 2, 4, 6 and 24 hrs post-dose) and week 8 (0, 0.5, 1, 1.5, 2, 4, 6 and 24 hrs post-dose) | 
| Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration in Fasted vs. Fed | Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis. | Week 4 (0, 0.5, 1, 1.5, 2, 4, 6 and 24 hrs post-dose) and week 8 (0, 0.5, 1, 1.5, 2, 4, 6 and 24 hrs post-dose) | 
| Change From Baseline to Week 8 in Plasma Renin Activity (PRA) | Biomarkers related to hypertension-related pathophysiology were evaluated in this study, such as plasma renin activity (PRA) . Blood samples were taken at Visit 3 (baseline) and Visit 6 (week 8).The difference between baseline and week 8 was calculated. | Baseline, Week 8 | 
| Change From Baseline to Week 8 in Plasma Renin Concentration (PRC) | Biomarkers related to hypertension-related pathophysiology were evaluated in this study, such as plasma renin concentration (PRC). Blood samples were taken at Visit 3 (baseline) and Visit 6 (week 8). The difference between baseline and week 8 was calculated. | Baseline, Week 8 | 
| Number of Patients With Adverse Events, Serious Adverse Events and Death |  | 8 weeks | 
| Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Diastolic Blood Pressure (maDBP) | 24 hour ambulatory blood pressure measurement (ABPM) were taken twice, at baseline and at the end of 8 weeks. An Ambulatory Blood Pressure Monitoring device (ABPM) was attached to the non-dominant arm. The mean change of 24 hours maDBP from baseline to week 8 was estimated using an Analysis of Covariance (ANCOVA) model by using treatment, region as factors, and baseline as covariate. | Baseline, week 8 | 
| Percentage of Patients Achieving Blood Pressure Control | Patients achieving blood pressure control were patients who, at week 8, had a mean sitting systolic blood pressure (msSBP)/ mean sitting diastolic blood pressure (msDBP) < 140/90 mmHg | 8 weeks | 
| Change From Baseline (Visit 3) to End of Study (8 Weeks) in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | Sitting blood pressure (BP) was measured at trough (approximately 24 hours ± 3 hours post dose) and recorded at all study visits. At the first study visit, the BP was checked in both arms and the arm with higher systolic BP (SBP) was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for five minutes, systolic and diastolic blood pressures (msSBP and msDBP) were measured four times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 2 minute intervals and the mean of all four sitting blood pressure measurements was used as the average sitting office blood pressure for that visit. The analysis of covariance (ANCOVA) model used treatment, region as factors, and baseline as covariate. | Baseline, Week 8 | 
| Percentage of Patients Achieving a Successful Response in Systolic Blood Pressure Reduction | Successful response in systolic blood pressure reduction at end of 8-week treatment was defined as msSBP <140 mmHg or a reduction in msSBP ≥ 20 mmHg from baseline. | Baseline, Week 8 | 
| Pharmacokinetic (PK) of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration in Fasted vs. Fed | Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis. | Week 4 (0, 0.5, 1, 1.5, 2, 4, 6 and 24 hrs post-dose) and week 8 (0, 0.5, 1, 1.5, 2, 4, 6 and 24 hrs post-dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food effect, hypertension, aliskiren