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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Aliskiren

• Study Type: Interventional
• Enrollment (Actual): 589
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • Novartis Investigative Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1A 3R5
      • Novartis Investigative Site
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M9W 4L6
      • Novartis Investigative Site
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Novartis Investigative Site
    • Sainte-Foy, Quebec, Canada, G1W 4R4
      • Novartis Investigative Site
• Italy
  • IS
    • Pozzilli, IS, Italy, 86077
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • SS
    • Sassari, SS, Italy, 07100
      • Novartis Investigative Site
• Puerto Rico
  • Carolina, Puerto Rico, 00983
    • Novartis Investigative Site
  • Cidra, Puerto Rico, 00739
    • Novartis Investigative Site
  • Manati, Puerto Rico, 00674
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 821 07
    • Novartis Investigative Site
  • Martin, Slovakia, 036 01
    • Novartis Investigative Site
  • Presov, Slovakia, 080 01
    • Novartis Investigative Site
  • Sala, Slovakia, 927 03
    • Novartis Investigative Site
  • Zvolen, Slovakia, 960 01
    • Novartis Investigative Site
  • Slovak Republic
    • Kosice, Slovak Republic, Slovakia, 040 11
      • Novartis Investigative Site
    • Svidnik, Slovak Republic, Slovakia, 08901
      • Novartis Investigative Site
  • Slovak republic
    • Banská Bystrica, Slovak republic, Slovakia, 97405
      • Novartis Investigative Site
    • Bratislava, Slovak republic, Slovakia, 83299
      • Novartis Investigative Site
    • Kosice, Slovak republic, Slovakia, 04001
      • Novartis Investigative Site
    • Nitra, Slovak republic, Slovakia, 95201
      • Novartis Investigative Site
    • Rimavska Sobota, Slovak republic, Slovakia, 97901
      • Novartis Investigative Site
    • Senec, Slovak republic, Slovakia, 90301
      • Novartis Investigative Site
    • Snina, Slovak republic, Slovakia, 09601
      • Novartis Investigative Site
    • Trnava, Slovak republic, Slovakia, 91701
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08905
      • Novartis Investigative Site
    • Centelles, Cataluña, Spain, 08540
      • Novartis Investigative Site
    • Corbera de Llobregat, Cataluña, Spain, 08757
      • Novartis Investigative Site
    • Hostalets de Balenya, Cataluña, Spain, 08550
      • Novartis Investigative Site
    • Vic, Cataluña, Spain, 08500
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alzira, Comunidad Valenciana, Spain, 46600
      • Novartis Investigative Site
    • Quart de Poblet, Comunidad Valenciana, Spain, 46930
      • Novartis Investigative Site
• Taiwan
  • Changhua, Taiwan, 500
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 114
    • Novartis Investigative Site
  • Taiwan, ROC
    • Taipei, Taiwan, ROC, Taiwan, 112
      • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90057
      • Novartis Investigative Site
    • Riverside, California, United States, 92506
      • Novartis Investigative Site
    • Santa Monica, California, United States, 90404
      • Novartis Investigative Site
    • Walnut Creek, California, United States, 94598
      • Novartis Investigative Site
    • Westlake Village, California, United States, 91361
      • Novartis Investigative Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Novartis Investigative Site
    • Miami, Florida, United States, 33169
      • Novartis Investigative Site
    • South Miami, Florida, United States, 33143
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Novartis Investigative Site
    • Chicago, Illinois, United States, 60610
      • Novartis Investigative Site
  • Indiana
    • Evansville, Indiana, United States, 47712
      • Novartis Investigative Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novartis Investigative Site
  • Louisiana
    • Opelousas, Louisiana, United States, 70570
      • Novartis Investigative Site
  • Minnesota
    • Chaska, Minnesota, United States, 55318
      • Novartis Investigative Site
    • Edina, Minnesota, United States, 55435
      • Novartis Investigative Site
    • St. Paul, Minnesota, United States, 55114
      • Novartis Investigative Site
  • Mississippi
    • Jackson, Mississippi, United States, 39209
      • Novartis Investigative Site
    • Picayune, Mississippi, United States, 39466
      • Novartis Investigative Site
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Novartis Investigative Site
    • Greensboro, North Carolina, United States, 27401
      • Novartis Investigative Site
    • Greensboro, North Carolina, United States, 27408
      • Novartis Investigative Site
    • Salisbury, North Carolina, United States, 28144
      • Novartis Investigative Site
    • Shelby, North Carolina, United States, 28152
      • Novartis Investigative Site
    • Winston-Salem, North Carolina, United States, 27103
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43213
      • Novartis Investigative Site
    • Lyndhurst, Ohio, United States, 44124
      • Novartis Investigative Site
    • Marion, Ohio, United States, 43302
      • Novartis Investigative Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Novartis Investigative Site
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Novartis Investigative Site
    • Oregon City, Oregon, United States, 97045
      • Novartis Investigative Site
    • Portland, Oregon, United States, 97239
      • Novartis Investigative Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Novartis Investigative Site
  • Texas
    • Beaumont, Texas, United States, 77702
      • Novartis Investigative Site
    • Houston, Texas, United States, 77081
      • Novartis Investigative Site
    • Lake Jackson, Texas, United States, 77566
      • Novartis Investigative Site
    • Pasadena, Texas, United States, 77504
      • Novartis Investigative Site
  • Utah
    • Centerville, Utah, United States, 84104
      • Novartis Investigative Site
  • Virginia
    • Arlington, Virginia, United States, 22203
      • Novartis Investigative Site
    • Ettrick, Virginia, United States, 23803
      • Novartis Investigative Site
    • Midlothian, Virginia, United States, 23114
      • Novartis Investigative Site
  • Washington
    • Port Orchard, Washington, United States, 98366
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
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)
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: April 2, 2012
• First Submitted That Met QC Criteria: April 2, 2012
• First Posted (Estimate): April 4, 2012

Study Record Updates

• Last Update Posted (Estimate): January 22, 2014
• Last Update Submitted That Met QC Criteria: January 15, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Food effect, hypertension, aliskiren
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CSPP100A2413; 2011-005297-36 (EudraCT Number)