Efficacy and Safety of SPA100 (Fixed-dose Combination of Aliskiren/Amlodipine) in Patients With Essential Hypertension

Phase 3

Completed

Conditions: Essential Hypertension

Interventions: Drug: Aliskiren 150 mg
Drug: Amlodipine 2.5 mg
Drug: Aliskiren/Amlodipine 150/2.5 mg
Drug: Aliskiren/amlodipine 150/5 mg
Drug: Placebo of Amlodipine
Drug: Placebo of Aliskiren
Drug: Placebo of Aliskiren/amlodipine 150/2.5 mg
Drug: Placebo of Aliskiren/amlodipine 150/5 mg

Registration Number: NCT01237223

Lead Sponsor: Novartis

Brief Summary: The purpose of the study was to evaluate the efficacy (blood pressure lowering effect) and safety of SPA100 (Fixed-dose Combination of Aliskiren and Amlodipine) in patients with essential hypertension (mean sitting diastolic blood pressure \[msDBP\] ≥ 95 mmHg and \< 110 mmHg and mean sitting systolic blood pressure \[msSBP\] ≥ 140 mmHg ). This study was conducted to support registration of the fixed-dose combination of aliskiren and amlodipine for the treatment of hypertension in Japan.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1342

Inclusion Criteria

Patients with essential hypertension (msDBP ≥ 95 mmHg and < 110 mmHg and msSBP ≥140 mmHg )
Outpatients

Exclusion Criteria

Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
History of allergy or hypersensitivity to renin inhibitors, calcium channel blockers
History or evidence of a secondary hypertension

Other protocol-defined inclusion/exclusion criteria applied

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Aliskiren 150 mg	Aliskiren 150 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Aliskiren 150 mg tablet once daily (o.d)+ placebo of two amlodipine 2.5 mg capsule o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 5 mg	Amlodipine 2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received amlodipine 5 mg (two amlodipine 2.5 mg capsules o.d.)+ placebo of aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. , aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren 150 mg	Placebo of Amlodipine	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Aliskiren 150 mg tablet once daily (o.d)+ placebo of two amlodipine 2.5 mg capsule o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 5 mg	Placebo of Aliskiren	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received amlodipine 5 mg (two amlodipine 2.5 mg capsules o.d.)+ placebo of aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. , aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/2.5 mg	Placebo of Aliskiren	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/2.5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/5 mg	Placebo of Aliskiren	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.
Placebo	Placebo of Aliskiren	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. In single blind run-in (4 weeks) and double blind treatment period (8 weeks), patients were received matching placebo of aliskiren/amlodipine 150/5 mg tablet, aliskiren/amlodipine 150/2.5 mg tablet, aliskiren 150 mg tablet and two amlodipine 2.5 mg capsules once daily.
Placebo	Placebo of Amlodipine	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. In single blind run-in (4 weeks) and double blind treatment period (8 weeks), patients were received matching placebo of aliskiren/amlodipine 150/5 mg tablet, aliskiren/amlodipine 150/2.5 mg tablet, aliskiren 150 mg tablet and two amlodipine 2.5 mg capsules once daily.
Placebo	Placebo of Aliskiren/amlodipine 150/2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. In single blind run-in (4 weeks) and double blind treatment period (8 weeks), patients were received matching placebo of aliskiren/amlodipine 150/5 mg tablet, aliskiren/amlodipine 150/2.5 mg tablet, aliskiren 150 mg tablet and two amlodipine 2.5 mg capsules once daily.
Placebo	Placebo of Aliskiren/amlodipine 150/5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. In single blind run-in (4 weeks) and double blind treatment period (8 weeks), patients were received matching placebo of aliskiren/amlodipine 150/5 mg tablet, aliskiren/amlodipine 150/2.5 mg tablet, aliskiren 150 mg tablet and two amlodipine 2.5 mg capsules once daily.
Aliskiren 150 mg	Placebo of Aliskiren/amlodipine 150/2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Aliskiren 150 mg tablet once daily (o.d)+ placebo of two amlodipine 2.5 mg capsule o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Aliskiren 150 mg	Placebo of Aliskiren/amlodipine 150/5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Aliskiren 150 mg tablet once daily (o.d)+ placebo of two amlodipine 2.5 mg capsule o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 2.5 mg	Amlodipine 2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Amlodipine 2.5 mg capsule once daily (o.d)+ placebo of amlodipine 2.5 mg capsule o.d., Aliskiren 150 mg o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 2.5 mg	Placebo of Aliskiren	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Amlodipine 2.5 mg capsule once daily (o.d)+ placebo of amlodipine 2.5 mg capsule o.d., Aliskiren 150 mg o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 2.5 mg	Placebo of Amlodipine	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Amlodipine 2.5 mg capsule once daily (o.d)+ placebo of amlodipine 2.5 mg capsule o.d., Aliskiren 150 mg o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 2.5 mg	Placebo of Aliskiren/amlodipine 150/2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Amlodipine 2.5 mg capsule once daily (o.d)+ placebo of amlodipine 2.5 mg capsule o.d., Aliskiren 150 mg o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 2.5 mg	Placebo of Aliskiren/amlodipine 150/5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Amlodipine 2.5 mg capsule once daily (o.d)+ placebo of amlodipine 2.5 mg capsule o.d., Aliskiren 150 mg o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period.
Amlodipine 5 mg	Placebo of Aliskiren/amlodipine 150/2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received amlodipine 5 mg (two amlodipine 2.5 mg capsules o.d.)+ placebo of aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. , aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.
Amlodipine 5 mg	Placebo of Aliskiren/amlodipine 150/5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received amlodipine 5 mg (two amlodipine 2.5 mg capsules o.d.)+ placebo of aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. , aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/2.5 mg	Aliskiren/Amlodipine 150/2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/2.5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/2.5 mg	Placebo of Amlodipine	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/2.5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/2.5 mg	Placebo of Aliskiren/amlodipine 150/5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/2.5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/5 mg	Aliskiren/amlodipine 150/5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/5 mg	Placebo of Amlodipine	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.
Aliskiren/amlodipine 150/5 mg	Placebo of Aliskiren/amlodipine 150/2.5 mg	In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) to End of Study (Week 8)	Baseline, Week 8	Sitting blood pressure was measured at trough (24 hours ± 2 hours post dose) and recorded at all study visits. At the first study visit, blood pressure was measured in both arms and the arm with highest sitting DBP was found and used for all subsequent readings throughout the study. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these three sitting blood pressure measurements were used as the average sitting blood pressure for that visit. Analysis of covariance (ANCOVA) model contained treatment and region as two factors and baseline as a covariate.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) to End of Study (Week 8)	Baseline, Week 8	Sitting blood pressure was measured at trough (24 hours ± 2 hours post dose) and recorded at all study visits. At the first study visit, blood pressure was measured in both arms and the arm with highest sitting DBP was found and used for all subsequent readings throughout the study. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these three sitting blood pressure measurements were used as the average sitting blood pressure for that visit. Analysis of covariance (ANCOVA) model contained treatment and region as two factors and baseline as a covariate.
Percentage of Participants Achieving Blood Pressure Control at Endpoint	8 weeks	Blood pressure control is defined as having as a msDBP \< 90 mmHg and a msSBP \< 140 mmHg.
Percentage of Participants Achieving a Successful Response Rate	8 weeks	The response rate was defined as percentage of participants who achieved msDBP \< 90 mmHg or its reduction ≥ 10 mmHg from baseline to endpoint.
Number of Participants With Adverse Events, Serious Adverse Events and Death	8 weeks	Number of patients with adverse events regardless of study drug relationship during the double-blind treatment period were reported. Serious adverse events of double blind period were reported.