Trial Outcomes & Findings for A Long Term Safety Study to Test the Combination of Aliskiren/ Amlodipine / Hydrochlorothiazide in Participants With Essential Hypertension (NCT NCT00667719)

Last Updated: 2021-06-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

564 participants

Primary outcome timeframe

54 weeks

Results posted on

2021-06-07

Participant Flow

Participants with essential hypertension were enrolled in the study at 82 investigative sites worldwide from 5 June 2008 to 5 October 2009.

A total of 635 participants entered the washout period, of which 564 participants met the study entry criteria and entered the study treatment phase.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	564
Overall Study COMPLETED	493
Overall Study NOT COMPLETED	71

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	39
Overall Study Abnormal Test Procedure	1
Overall Study Unsatisfactory Therapeutic Effect	3
Overall Study Protocol Violation	3
Overall Study Withdrawal by Subject	17
Overall Study Lost to Follow-up	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aliskiren /Amlodipine/Hydrochlorothiazide n=564 Participants Participants received aliskiren 300 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.
Age, Continuous	55.9 years STANDARD_DEVIATION 11.34 • n=5 Participants
Sex: Female, Male Female	238 Participants n=5 Participants
Sex: Female, Male Male	326 Participants n=5 Participants

PRIMARY outcome

Timeframe: 54 weeks

Population: Treated Population consisted of all participants who received at least one dose of trial medication.

Outcome measures

Outcome measures
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 Participants Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg n=561 Participants Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg n=556 Participants Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death Any Adverse Events	57 Participants	54 Participants	255 Participants
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death Serious Adverse Events	0 Participants	1 Participants	14 Participants
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death Death	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 28 and 54 endpoint

Population: Treated Population consisted of all participants who received at least one dose of trial medication. Number analyzed is the number of participants with data available at both baseline and post-baseline time points.

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.

Outcome measures

Outcome measures
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 Participants Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Baseline	101.8 mmHg Standard Deviation 7.74	—	—
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Change from Baseline to Week 28 Endpoint	-20.3 mmHg Standard Deviation 8.92	—	—
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Change from Baseline to Week 54 Endpoint	-21.8 mmHg Standard Deviation 8.66	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 28 and 54 endpoints

Outcome measures

Outcome measures
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 Participants Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Baseline	166.1 millimeters of mercury Standard Deviation 11.59	—	—
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Change from baseline to Week 28 Endpoint	-34.2 millimeters of mercury Standard Deviation 14.16	—	—
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Change from Baseline to Week 54 Endpoint	-37.3 millimeters of mercury Standard Deviation 14.63	—	—

SECONDARY outcome

Timeframe: Weeks 28 and 54 endpoints

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.

Outcome measures

Outcome measures
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 Participants Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Percentage of Participants Achieving the Blood Pressure Control Target of <140/90 mmHg Week 28 Endpoint	69.1 percentage of participants	—	—
Percentage of Participants Achieving the Blood Pressure Control Target of <140/90 mmHg Week 54 Endpoint	77.1 percentage of participants	—	—

SECONDARY outcome

Timeframe: Weeks 28 and 54 endpoints

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.

Outcome measures

Outcome measures
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 Participants Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Diastolic Blood Pressure Week 28 Endpoint	91.8 percentage of participants	—	—
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Diastolic Blood Pressure Week 54 Endpoint	96.6 percentage of participants	—	—

SECONDARY outcome

Timeframe: Weeks 28 and 54 endpoints

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.

Outcome measures

Outcome measures
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 Participants Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Systolic Blood Pressure Week 28 Endpoint	90.2 percentage of participants	—	—
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Systolic Blood Pressure Week 54 Endpoint	93.7 percentage of participants	—	—

Adverse Events

Aliskiren/Hydrochlorothiazide 300/12.5 mg

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg

Serious events: 14 serious events

Other events: 141 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 participants at risk Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg n=561 participants at risk Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg n=556 participants at risk Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Cardiac disorders Atrial fibrillation	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Cardiac disorders Palpitations	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.36% 2/556 • From Baseline up to 54 weeks.
Gastrointestinal disorders Inguinal hernia, obstructive	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
General disorders Non-cardiac chest pain	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Infections and infestations Bronchitis	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Infections and infestations Sinusitis	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/564 • From Baseline up to 54 weeks.	0.18% 1/561 • From Baseline up to 54 weeks.	0.00% 0/556 • From Baseline up to 54 weeks.
Nervous system disorders Carotid artery stenosis	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Nervous system disorders Cerebrovascular accident	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Nervous system disorders Cervical myelopathy	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Nervous system disorders Headache	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Nervous system disorders Presyncope	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Psychiatric disorders Drug dependence	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Renal and urinary disorders Renal failure	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Vascular disorders Peripheral ischaemia	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.
Vascular disorders Venous thrombosis	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	0.18% 1/556 • From Baseline up to 54 weeks.

Other adverse events

Other adverse events
Measure	Aliskiren/Hydrochlorothiazide 300/12.5 mg n=564 participants at risk Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg, orally with water, once daily in the morning, for one week, at Week 1.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg n=561 participants at risk Following Week 1, participants received combination of aliskiren 300 mg plus amolodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. All study medications were taken orally with water, once daily in the morning.	Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg n=556 participants at risk Following Week 2, participants were force titrated up to aliskiren 300 mg plus amolodipine 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.
Gastrointestinal disorders Diarrhoea	0.89% 5/564 • From Baseline up to 54 weeks.	0.18% 1/561 • From Baseline up to 54 weeks.	2.0% 11/556 • From Baseline up to 54 weeks.
General disorders Oedema peripheral	0.18% 1/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	9.4% 52/556 • From Baseline up to 54 weeks.
Infections and infestations Bronchitis	0.35% 2/564 • From Baseline up to 54 weeks.	0.53% 3/561 • From Baseline up to 54 weeks.	2.9% 16/556 • From Baseline up to 54 weeks.
Infections and infestations Influenza	0.00% 0/564 • From Baseline up to 54 weeks.	0.00% 0/561 • From Baseline up to 54 weeks.	2.7% 15/556 • From Baseline up to 54 weeks.
Infections and infestations Nasopharyngitis	0.53% 3/564 • From Baseline up to 54 weeks.	0.36% 2/561 • From Baseline up to 54 weeks.	3.6% 20/556 • From Baseline up to 54 weeks.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/564 • From Baseline up to 54 weeks.	0.36% 2/561 • From Baseline up to 54 weeks.	2.2% 12/556 • From Baseline up to 54 weeks.
Nervous system disorders Headache	1.8% 10/564 • From Baseline up to 54 weeks.	1.1% 6/561 • From Baseline up to 54 weeks.	2.7% 15/556 • From Baseline up to 54 weeks.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER