A Long Term Safety Study to Test the Combination of Aliskiren/ Amlodipine / Hydrochlorothiazide in Participants With Essential Hypertension

A 28 to 54-week, Open-label, Multicenter Study to Assess the Long-term Safety and Tolerability of the Combination of Aliskiren / Amlodipine / Hydrochlorothiazide in Patients With Essential Hypertension

This study tested the safety of the combination of aliskiren/amlodipine/hydrochlorothiazide in participants with essential hypertension.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Aliskiren; Drug: Amlodipine; Drug: Hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Actual): 564
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Belgium, Belgium
    • Investigative Site
• Egypt
  • Egypt, Egypt
    • Investigative Site
• Germany
  • Germany, Germany
    • Investigative Site
• Poland
  • Poland, Poland
    • Investigative Site
• Slovakia
  • Slovakia, Slovakia
    • Investigative Site
• Spain
  • Spain, Spain
    • Investigative Site
• Turkey
  • Turkey, Turkey
    • Investigative Site
• United States
  • Texas
    • Houston, Texas, United States
      • 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:

• Outpatients 18 years of age or older
• Male or female participants are eligible.

• Mean sitting diastolic blood pressure (msDBP) and mean sitting systolic blood pressure (msSBP) Requirements:

  • For newly diagnosed/untreated participants, msDBP ≥ 100 and < 120 millimeters of mercury (mmHg), and/or msSBP ≥ 160 and < 200 mmHg at Visit 1 and Visit 2.
  • For previously treated participants, msDBP ≥ 100 and < 120 mmHg, and/or msSBP ≥ 160 and < 200 mmHg at Visit 2, Visit 3, or Visit 4.
• For participants requiring tapering off their previous antihypertensive medication, they must meet the above criteria and completely discontinue all antihypertensive treatment prior to entering the treatment phase of the study.
• Participants who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent).

Exclusion Criteria:

• Inability to discontinue all prior antihypertensive medications safely for a period of 1 week to 4 weeks as required by the protocol.
• Participants on three antihypertensive drugs with msDBP ≥ 110 mmHg and/or msSBP ≥ 180 mmHg at Visit 1.
• Participants on four or more antihypertensive drugs at Visit 1.
• Participants with an msSBP ≥ 200 and msDBP ≥ 120 mmHg anytime during the washout period of the study Visit 1-4 must be discontinued from the study.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (>= 5 milli-international units per milliliter mIU/mL).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Aliskiren/Amlodipine/Hydrochlorothiazide; Participants received aliskiren 300 milligrams (mg) plus hydrochlorothiazide 12.5 mg for one week, at Week 1 followed by combination of aliskiren 300 mg plus amlodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. Following Week 2, participants were force titrated up to aliskiren 300 mg plus amlodipine 10 mg plus hydrochlorothiazide 25 mg for 26 to 52 weeks (Weeks 28 to 54). All study medications were taken orally with water, once daily in the morning.

Drug: Aliskiren; 300 mg tablet; Drug: Amlodipine; 5 mg tablet; Drug: Hydrochlorothiazide; 12.5 mg and 25 mg capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death	An AE was defined as the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug, even if the event is not considered to be related to study drug. An SAE was defined as an event which was fatal or life-threatening, resulted in persistent or significant disability/incapacity, constituted a congenital anomaly/birth defect, required inpatient hospitalization or prolongation of existing hospitalization, was medically significant, i.e. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above.	54 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the participant in a sitting position for five minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.	Baseline, Weeks 28 and 54 endpoint
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the participant in a sitting position for five minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.	Baseline, Weeks 28 and 54 endpoints
Percentage of Participants Achieving the Blood Pressure Control Target of <140/90 mmHg	Blood pressure control was defined as having a mean sitting diastolic blood pressure <90 mmHg and a mean sitting systolic blood pressure <140 mmHg. Percentage of participants achieving the blood pressure control of < 140/90 mmHg were reported. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28 and Week 54 Endpoint was the last non-missing measurement value after Week 28.	Weeks 28 and 54 endpoints
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Diastolic Blood Pressure	Diastolic Blood pressure response was defined as a mean sitting diastolic blood pressure <90 mmHg or a >=10 mmHg reduction from baseline value. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.	Weeks 28 and 54 endpoints
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Systolic Blood Pressure	Systolic blood pressure response was defined as a mean sitting systolic blood pressure <140 mmHg or a >=20 mmHg reduction from baseline value. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.	Weeks 28 and 54 endpoints

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Murray AV, Koenig W, Garcia-Puig J, Patel S, Uddin A, Zhang J. Safety and efficacy of aliskiren/amlodipine/hydrochlorothiazide triple combination in patients with moderate to severe hypertension: a 54-week, open-label study. J Clin Hypertens (Greenwich). 2012 Dec;14(12):821-7. doi: 10.1111/j.1751-7176.2012.00706.x. Epub 2012 Aug 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 5, 2008
• Primary Completion (ACTUAL): October 5, 2009
• Study Completion (ACTUAL): October 5, 2009

Study Registration Dates

• First Submitted: April 24, 2008
• First Submitted That Met QC Criteria: April 25, 2008
• First Posted (ESTIMATE): April 28, 2008

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Essential hypertension; High blood pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Sodium Chloride Symporter Inhibitors; Amlodipine; Hydrochlorothiazide
• Other Study ID Numbers: CSAH100A2301; 2008-001242-10 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No