Efficacy and Safety of Once Daily Dosing of Aliskiren (300 mg (qd) Once a Day) to Twice Daily Dosing of Aliskiren (150 mg (Bid) Twice a Day) in Treating Moderate Hypertension.

A 10 Week, Randomized, Double-blind, Parallel Group, Multi-center Study to Evaluate the Efficacy and Safety of Once Daily Dosing of Aliskiren (300 mg qd) to Twice Daily Dosing of Aliskiren (150 mg Bid) in Patients With Essential Hypertension.

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00654875

Enrollment

328

Registered

2008-04-09

Start date

2008-03-31

Completion date

2008-11-30

Last updated

2011-06-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Essential Hypertension

Keywords

Essential Hypertension

Brief summary

This study will compare the safety and efficacy of once daily dosing of aliskiren to twice daily dosing of aliskiren in patients with moderate hypertension

Interventions

DRUGAliskiren

Aliskiren supplied in 150 mg and 300 mg tablets.

DRUGPlacebo to Aliskiren

Placebo to Aliskiren matching 150 and 300 mg tablets

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Have diagnosis of uncomplicated essential hypertension; newly diagnosed or who have not received antihypertension medication within 4 weeks of visit 1 must have an office cuff mean sitting Diastolic Blood pressure (msDBP) \> 100 mmHg and \< 110 mmHg at visit 1. If patient is receiving antihypertensive treatment, must have a cuff msDBP \> 95 mmHg and \< 110 mmHg at visit 1 * Prior to randomization, all patients must have an office cuff msDBP \>or= 100 mmHg and \<or = 110 mmHg.

Exclusion criteria

* Participation in another aliskiren trial or previous treatment with aliskiren during last 6 months and who qualified to be randomized or enrolled into the active drug treatment period * Pregnant or nursing women * Women of child bearing potential unwilling to use protocol specific contraceptive methods * Office cuff blood pressure of msDBP ≥ 112 mmHg and/or mean sitting Systolic Blood Pressure (msSBP) ≥ 200 mmHg). * Secondary form of hypertension * History of heart failure New York Heart Association (NYHA Class II, III and IV) * Previous history of hypertensive encephalopathy or stroke, transient ischemic attack (TIA), heart attack, coronary bypass surgery or any percutaneous coronary intervention (PCI) * Elevated Serum potassium (\> or = 5.3 mEq/L (mmol/L) at Visit 1 * Type 1 or Type 2 diabetes mellitus not well controlled * Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Week 6 in the Mean 24-hour Ambulatory Diastolic Blood Pressure (MADBP)	Baseline, Week 6	An Ambulatory Blood Pressure Monitoring (ABPM) device was attached to the non-dominant arm of the participant. The mean of Blood Pressure readings during the 24 hour period were calculated. The difference of the 24 hour MADBP from baseline to the 24 hour MADBP at 6 weeks was calculated using an Analysis of covariance (ANCOVA) model with baseline mean 24 hour ambulatory diastolic blood pressure as a covariate.

Secondary

Measure	Time frame	Description
Change From Baseline to Week 6 in the Mean Ambulatory Systolic Blood Pressure (MASBP) During the Last Three Hours of the 24-hour Dosing Period	Baseline, Week 6	An Ambulatory Blood Pressure Monitoring (ABPM) device was attached to the non-dominant arm of the participant. The mean of Blood Pressure readings during the 22-24 hour period were calculated. The difference from the last 3 hours MASBP at baseline to the last 3 hour MASBP at Week 6 was calculated using an ANCOVA model with baseline mean 24 hour ambulatory systolic blood pressure as a covariate.
Change From Baseline to Week 6 in the Mean 24-hour Ambulatory Systolic Blood Pressure (MASBP)	Baseline, Week 6	An Ambulatory Blood Pressure Monitoring (ABPM) device was attached to the non-dominant arm of the participant. The mean of Blood Pressure readings during the 24 hour period were calculated. The difference of the 24 hour MASBP from baseline to the 24 hour MASBP at 6 weeks was calculated using an ANCOVA model with baseline mean 24 hour ambulatory systolic blood pressure as a covariate.
Change From Baseline to Week 6 in the Mean Ambulatory Diastolic Blood Pressure (MADBP) During the Last 3 Hours of the 24-hour Dosing Period	Baseline, Week 6	An Ambulatory Blood Pressure Monitoring (ABPM) device was attached to the non-dominant arm of the participant. The mean of Blood Pressure readings during the 22-24 hour period were calculated. The difference from the last 3 hours MADBP at baseline to the last 3 hour MADBP at Week 6 was calculated using an ANCOVA model with baseline mean 24 hour ambulatory diastolic blood pressure as a covariate.
Percentage of Participants Achieving Blood Pressure Control at Week 6	Week 6	After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using a calibrated standard sphygmomanometer. The mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure at visit 3 (week 6). Blood pressure control was defined as having a mean sitting diastolic blood pressure (msDBP) \<90 mm Hg and a mean sitting systolic blood pressure (msSBP) \<140 mm Hg.
Percentage of Participants Achieving Blood Pressure Control at the End of the Study (Week 10)	Week 10	After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using a calibrated standard sphygmomanometer. The mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure at visit 4 (week 10). Blood pressure control was defined as having a mean sitting diastolic blood pressure (msDBP) \<90 mm Hg and a mean sitting systolic blood pressure (msSBP) \<140 mm Hg.
Change From Baseline to Week 6 in the Mean Sitting Systolic and Mean Sitting Diastolic Blood Pressure	Baseline, Week 6	After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using a calibrated standard sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A negative number indicates lowered blood pressure. The ANCOVA model used baseline as a covariate.

Countries

Germany, Spain, United States

Participant flow

Participants by arm

Arm	Count
Aliskiren 300 mg (Once a Day) Participants received Aliskiren 300 mg tablet + Placebo to Aliskiren matching 150 mg tablet daily in the morning and Placebo to Aliskiren matching 150 mg tablet daily in the evening for a total of 10 weeks.	164
Aliskiren 150 mg (Twice a Day) Participants received Aliskiren 150 mg tablet + Placebo to Aliskiren matching 300 mg tablet daily in the morning and Aliskiren 150 mg tablet daily in the evening for the first 6 weeks then for the next 4 weeks received Aliskiren 300 mg tablet + Placebo to Aliskiren matching 150 mg tablet daily in the morning and Placebo to Aliskiren matching 150 mg tablet daily in the evening.	164
Total	328

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Abnormal Test Procedure Result(s)	1	0
Overall Study	Administrative Problems	1	0
Overall Study	Adverse Event	5	5
Overall Study	Lack of Efficacy	2	2
Overall Study	Lost to Follow-up	1	3
Overall Study	Protocol Violation	3	3
Overall Study	Withdrawal by Subject	4	4

Baseline characteristics

Characteristic	Aliskiren 300 mg (Once a Day)	Aliskiren 150 mg (Twice a Day)	Total
Age Continuous	55 years STANDARD_DEVIATION 10.3	54 years STANDARD_DEVIATION 10.2	54 years STANDARD_DEVIATION 10.3
Sex: Female, Male Female	63 Participants	77 Participants	140 Participants
Sex: Female, Male Male	101 Participants	87 Participants	188 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 164	0 / 164
serious Total, serious adverse events	2 / 164	2 / 164

Outcome results

Primary

Change From Baseline to Week 6 in the Mean 24-hour Ambulatory Diastolic Blood Pressure (MADBP)

An Ambulatory Blood Pressure Monitoring (ABPM) device was attached to the non-dominant arm of the participant. The mean of Blood Pressure readings during the 24 hour period were calculated. The difference of the 24 hour MADBP from baseline to the 24 hour MADBP at 6 weeks was calculated using an Analysis of covariance (ANCOVA) model with baseline mean 24 hour ambulatory diastolic blood pressure as a covariate.

Time frame: Baseline, Week 6