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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01570686
• Other study ID #: CSPP100A2413
• Secondary ID: 2011-005297-36
• Status: Completed
• Phase: Phase 4
• First received: April 2, 2012
• Last updated: January 15, 2014
• Start date: April 2012
• Est. completion date: November 2012

Study information

• Verified date: January 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Products and Food BranchEurope: European Medicines AgencyTaiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 589
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Aliskiren
Aliskiren 300 mg once daily

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Brampton	Ontario
Canada	Novartis Investigative Site	Mirabel	Quebec
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	St. John's	Newfoundland and Labrador
Canada	Novartis Investigative Site	Toronto	Ontario
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Pozzilli	IS
Italy	Novartis Investigative Site	Sassari	SS
Puerto Rico	Novartis Investigative Site	Carolina
Puerto Rico	Novartis Investigative Site	Cidra
Puerto Rico	Novartis Investigative Site	Manati
Slovakia	Novartis Investigative Site	Banská Bystrica	Slovak republic
Slovakia	Novartis Investigative Site	Bratislava	Slovak republic
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice	Slovak republic
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Nitra	Slovak republic
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Rimavska Sobota	Slovak republic
Slovakia	Novartis Investigative Site	Sala
Slovakia	Novartis Investigative Site	Senec	Slovak republic
Slovakia	Novartis Investigative Site	Snina	Slovak republic
Slovakia	Novartis Investigative Site	Svidnik	Slovak Republic
Slovakia	Novartis Investigative Site	Trnava	Slovak republic
Slovakia	Novartis Investigative Site	Zvolen
Spain	Novartis Investigative Site	Alzira	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Centelles	Cataluña
Spain	Novartis Investigative Site	Corbera de Llobregat	Cataluña
Spain	Novartis Investigative Site	Hostalets de Balenya	Cataluña
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Quart de Poblet	Comunidad Valenciana
Spain	Novartis Investigative Site	Vic	Cataluña
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
United States	Novartis Investigative Site	Arlington	Virginia
United States	Novartis Investigative Site	Beaumont	Texas
United States	Novartis Investigative Site	Centerville	Utah
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Chaska	Minnesota
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Coral Gables	Florida
United States	Novartis Investigative Site	Edina	Minnesota
United States	Novartis Investigative Site	Ettrick	Virginia
United States	Novartis Investigative Site	Eugene	Oregon
United States	Novartis Investigative Site	Evansville	Indiana
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Lake Jackson	Texas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Lyndhurst	Ohio
United States	Novartis Investigative Site	Marion	Ohio
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Midlothian	Virginia
United States	Novartis Investigative Site	Norman	Oklahoma
United States	Novartis Investigative Site	Opelousas	Louisiana
United States	Novartis Investigative Site	Oregon City	Oregon
United States	Novartis Investigative Site	Pasadena	Texas
United States	Novartis Investigative Site	Picayune	Mississippi
United States	Novartis Investigative Site	Port Orchard	Washington
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Riverside	California
United States	Novartis Investigative Site	Salisbury	North Carolina
United States	Novartis Investigative Site	Santa Monica	California
United States	Novartis Investigative Site	Shelby	North Carolina
United States	Novartis Investigative Site	South Miami	Florida
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	St. Paul	Minnesota
United States	Novartis Investigative Site	Topeka	Kansas
United States	Novartis Investigative Site	Walnut Creek	California
United States	Novartis Investigative Site	Westlake Village	California
United States	Novartis Investigative Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Puerto Rico,  Slovakia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	Number of Patients With Adverse Events, Serious Adverse Events and Death		8 weeks	Yes