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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01570686
First received: April 2, 2012
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Aliskiren
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Systolic Blood Pressure (maSBP) [ Time Frame: Baseline, week 8 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Diastolic Blood Pressure (maDBP) [ Time Frame: Baseline, week 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients Achieving Blood Pressure Control [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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

  • 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) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients Achieving a Successful Response in Systolic Blood Pressure Reduction [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    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.

  • Pharmacokinetic (PK) of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration in Fasted vs. Fed [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.

  • 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.

  • Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration in Fasted vs. Fed [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.

  • Change From Baseline to Week 8 in Plasma Renin Activity (PRA) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 8 in Plasma Renin Concentration (PRC) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With Adverse Events, Serious Adverse Events and Death [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 589
Study Start Date: April 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aliskiren: Fed
Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast
Drug: Aliskiren
Aliskiren 300 mg once daily
Other Name: Tekturna, rasilez
Experimental: Aliskiren: Fasting
Aliskiren 300 mg once daily taken after after an overnight fast
Drug: Aliskiren
Aliskiren 300 mg once daily
Other Name: Tekturna, rasilez

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01570686

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United States, California
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Los Angeles, California, United States, 90057
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Riverside, California, United States, 92506
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Santa Monica, California, United States, 90404
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Westlake Village, California, United States, 91361
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01570686     History of Changes
Other Study ID Numbers: CSPP100A2413, 2011-005297-36
Study First Received: April 2, 2012
Results First Received: November 10, 2013
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Products and Food Branch
Europe: European Medicines Agency
Taiwan: Department of Health

Keywords provided by Novartis:
Food effect, hypertension, aliskiren

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 23, 2014