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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01570686
• Collaborator: (none)
• Enrollment: 589
• Locations: 83
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 7.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Aliskiren	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 589 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aliskiren: Fed Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Drug: Aliskiren; Aliskiren 300 mg once daily; Other Names: Tekturna, rasilez
Experimental: Aliskiren: Fasting Aliskiren 300 mg once daily taken after after an overnight fast	Drug: Aliskiren; Aliskiren 300 mg once daily; Other Names: Tekturna, rasilez

Outcome Measures

Primary Outcome Measures

1. Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Systolic Blood Pressure (maSBP) [Baseline, week 8]

   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.

Secondary Outcome Measures

1. Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Diastolic Blood Pressure (maDBP) [Baseline, week 8]

   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.

2. Percentage of Patients Achieving Blood Pressure Control [8 weeks]

   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

3. 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) [Baseline, Week 8]

   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.

4. Percentage of Patients Achieving a Successful Response in Systolic Blood Pressure Reduction [Baseline, Week 8]

   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.

5. Pharmacokinetic (PK) of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration in Fasted vs. Fed [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)]

   Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.

6. 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 [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)]

   Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.

7. Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration in Fasted vs. Fed [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)]

   Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.

8. Change From Baseline to Week 8 in Plasma Renin Activity (PRA) [Baseline, Week 8]

   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.

9. Change From Baseline to Week 8 in Plasma Renin Concentration (PRC) [Baseline, Week 8]

   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.

10. Number of Patients With Adverse Events, Serious Adverse Events and Death [8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

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Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Los Angeles	California	United States	90057
2	Novartis Investigative Site	Riverside	California	United States	92506
3	Novartis Investigative Site	Santa Monica	California	United States	90404
4	Novartis Investigative Site	Walnut Creek	California	United States	94598
5	Novartis Investigative Site	Westlake Village	California	United States	91361
6	Novartis Investigative Site	Coral Gables	Florida	United States	33134
7	Novartis Investigative Site	Miami	Florida	United States	33169
8	Novartis Investigative Site	South Miami	Florida	United States	33143
9	Novartis Investigative Site	Chicago	Illinois	United States	60607
10	Novartis Investigative Site	Chicago	Illinois	United States	60610
11	Novartis Investigative Site	Evansville	Indiana	United States	47712
12	Novartis Investigative Site	Topeka	Kansas	United States	66606
13	Novartis Investigative Site	Opelousas	Louisiana	United States	70570
14	Novartis Investigative Site	Chaska	Minnesota	United States	55318
15	Novartis Investigative Site	Edina	Minnesota	United States	55435
16	Novartis Investigative Site	St. Paul	Minnesota	United States	55114
17	Novartis Investigative Site	Jackson	Mississippi	United States	39209
18	Novartis Investigative Site	Picayune	Mississippi	United States	39466
19	Novartis Investigative Site	St. Louis	Missouri	United States	63141
20	Novartis Investigative Site	Charlotte	North Carolina	United States	28209
21	Novartis Investigative Site	Greensboro	North Carolina	United States	27401
22	Novartis Investigative Site	Greensboro	North Carolina	United States	27408
23	Novartis Investigative Site	Salisbury	North Carolina	United States	28144
24	Novartis Investigative Site	Shelby	North Carolina	United States	28152
25	Novartis Investigative Site	Winston-Salem	North Carolina	United States	27103
26	Novartis Investigative Site	Cincinnati	Ohio	United States	45246
27	Novartis Investigative Site	Columbus	Ohio	United States	43213
28	Novartis Investigative Site	Lyndhurst	Ohio	United States	44124
29	Novartis Investigative Site	Marion	Ohio	United States	43302
30	Novartis Investigative Site	Norman	Oklahoma	United States	73069
31	Novartis Investigative Site	Eugene	Oregon	United States	97404
32	Novartis Investigative Site	Oregon City	Oregon	United States	97045
33	Novartis Investigative Site	Portland	Oregon	United States	97239
34	Novartis Investigative Site	Knoxville	Tennessee	United States	37920
35	Novartis Investigative Site	Beaumont	Texas	United States	77702
36	Novartis Investigative Site	Houston	Texas	United States	77081
37	Novartis Investigative Site	Lake Jackson	Texas	United States	77566
38	Novartis Investigative Site	Pasadena	Texas	United States	77504
39	Novartis Investigative Site	Centerville	Utah	United States	84104
40	Novartis Investigative Site	Arlington	Virginia	United States	22203
41	Novartis Investigative Site	Ettrick	Virginia	United States	23803
42	Novartis Investigative Site	Midlothian	Virginia	United States	23114
43	Novartis Investigative Site	Port Orchard	Washington	United States	98366
44	Novartis Investigative Site	Moncton	New Brunswick	Canada	E1G 1A7
45	Novartis Investigative Site	St. John's	Newfoundland and Labrador	Canada	A1A 3R5
46	Novartis Investigative Site	Brampton	Ontario	Canada	L6T 0G1
47	Novartis Investigative Site	Toronto	Ontario	Canada	M9W 4L6
48	Novartis Investigative Site	Mirabel	Quebec	Canada	J7J 2K8
49	Novartis Investigative Site	Sainte-Foy	Quebec	Canada	G1W 4R4
50	Novartis Investigative Site	Pozzilli	IS	Italy	86077
51	Novartis Investigative Site	Pavia	PV	Italy	27100
52	Novartis Investigative Site	Sassari	SS	Italy	07100
53	Novartis Investigative Site	Carolina		Puerto Rico	00983
54	Novartis Investigative Site	Cidra		Puerto Rico	00739
55	Novartis Investigative Site	Manati		Puerto Rico	00674
56	Novartis Investigative Site	Banská Bystrica	Slovak republic	Slovakia	97405
57	Novartis Investigative Site	Bratislava	Slovak republic	Slovakia	83299
58	Novartis Investigative Site	Kosice	Slovak Republic	Slovakia	040 11
59	Novartis Investigative Site	Kosice	Slovak republic	Slovakia	04001
60	Novartis Investigative Site	Nitra	Slovak republic	Slovakia	95201
61	Novartis Investigative Site	Rimavska Sobota	Slovak republic	Slovakia	97901
62	Novartis Investigative Site	Senec	Slovak republic	Slovakia	90301
63	Novartis Investigative Site	Snina	Slovak republic	Slovakia	09601
64	Novartis Investigative Site	Svidnik	Slovak Republic	Slovakia	08901
65	Novartis Investigative Site	Trnava	Slovak republic	Slovakia	91701
66	Novartis Investigative Site	Bratislava		Slovakia	821 07
67	Novartis Investigative Site	Martin		Slovakia	036 01
68	Novartis Investigative Site	Presov		Slovakia	080 01
69	Novartis Investigative Site	Sala		Slovakia	927 03
70	Novartis Investigative Site	Zvolen		Slovakia	960 01
71	Novartis Investigative Site	Barcelona	Cataluña	Spain	08905
72	Novartis Investigative Site	Centelles	Cataluña	Spain	08540
73	Novartis Investigative Site	Corbera de Llobregat	Cataluña	Spain	08757
74	Novartis Investigative Site	Hostalets de Balenya	Cataluña	Spain	08550
75	Novartis Investigative Site	Vic	Cataluña	Spain	08500
76	Novartis Investigative Site	Alzira	Comunidad Valenciana	Spain	46600
77	Novartis Investigative Site	Quart de Poblet	Comunidad Valenciana	Spain	46930
78	Novartis Investigative Site	Madrid		Spain	28009
79	Novartis Investigative Site	Taipei	Taiwan, ROC	Taiwan	112
80	Novartis Investigative Site	Changhua		Taiwan	500
81	Novartis Investigative Site	Taichung		Taiwan	40447
82	Novartis Investigative Site	Taipei		Taiwan	10002
83	Novartis Investigative Site	Taipei		Taiwan	114

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01570686
• Other Study ID Numbers: CSPP100A2413; 2011-005297-36
• First Posted: Apr 4, 2012
• Last Update Posted: Jan 22, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Novartis Pharmaceuticals: Food effect, hypertension, aliskiren
• Additional relevant MeSH terms: Hypertension

Study Results

Participant Flow

Pre-assignment Detail	A total of 691 patients enrolled in the study with 590 patients randomized. 1 patient was mis-randomized and did not receive study medication, therefore 589 patients actually received study medication.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Period Title: Overall Study
STARTED	296	294
Safety and Full Analysis Set (FAS)	295	294
COMPLETED	274	278
NOT COMPLETED	22	16

Baseline Characteristics

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting	Total
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast	Total of all reporting groups
Overall Participants	296	294	590
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.7 (10.44)	56.1 (11.03)	55.9 (10.73)
Sex: Female, Male (Count of Participants)
Female	152 51.4%	126 42.9%	278 47.1%
Male	144 48.6%	168 57.1%	312 52.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Systolic Blood Pressure (maSBP)
Description	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.
Time Frame	Baseline, week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): consisted of all randomized patients. Mis-randomized patients were excluded from the FAS. Patients with ABPM measurements at both baseline and week 8 were included in this analysis.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	263	266
Least Squares Mean (Standard Error) [mmHg]	-7.03 (0.50)	-7.79 (0.50)

2. Secondary Outcome

Title	Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Diastolic Blood Pressure (maDBP)
Description	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.
Time Frame	Baseline, week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): consisted of all randomized patients. Mis-randomized patients were excluded from the FAS. Patients with ABPM measurements at both baseline and week 8 were included in this analysis.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	263	266
Least Squares Mean (Standard Error) [mmHg]	-4.01 (0.31)	-4.39 (0.31)

3. Secondary Outcome

Title	Percentage of Patients Achieving Blood Pressure Control
Description	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
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): consisted of all randomized patients. Mis-randomized patients were excluded from the FAS. Patients with mean sitting blood pressure measurement over 8 weeks were included in this analysis.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	293	294
Number [Percentage of patients]	44.7	41.5

4. Secondary Outcome

Title	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)
Description	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.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): consisted of all randomized patients. Mis-randomized patients were excluded from the FAS. Patients with official mean sitting blood pressure measurements both at baseline and week 8 were icluded in this analysis.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	293	294
Mean sitting SBP (msSBP)	-13.65 (0.85)	-13.98 (0.85)
Mean sitting DBP (msDBP)	-8.97 (0.50)	-8.56 (0.50)

5. Secondary Outcome

Title	Percentage of Patients Achieving a Successful Response in Systolic Blood Pressure Reduction
Description	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.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): consisted of all randomized patients. Mis-randomized patients were excluded from the FAS. Patients with mean sitting SBP measurement at baseline and over 8 weeks were included in this analysis.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	293	294
Number [Percentage of patients]	54.9	55.8

6. Secondary Outcome

Title	Pharmacokinetic (PK) of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration in Fasted vs. Fed
Description	Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetics set included all patients who had evaluable aliskiren concentration data with no protocol deviations that presumably affect PK results were included in the pharmacokinetic evaluations

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	46	53
Week 4 (Day 28) (N= 46, 52)	108 (153)	273 (276)
Week 8 (Day 56) (N= 42, 53)	102 (139)	252 (220)

7. Secondary Outcome

Title	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
Description	Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetics set included all patients who had evaluable aliskiren concentration data with no protocol deviations that presumably affect PK results were included in the pharmacokinetic evaluations.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	46	53
Week 4 (Day 28) (N= 44, 50)	872 (603)	1580 (1120)
Week 8 (Day 56) (N= 40, 51)	1100 (1620)	1540 (1120)

8. Secondary Outcome

Title	Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration in Fasted vs. Fed
Description	Blood samples were collected at Week 4 and Week 8 in a subset of patients (approximately 15% of each treatment group) for PK analysis.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetics set included all patients who had evaluable aliskiren concentration data with no protocol deviations that presumably affect PK results were included in the pharmacokinetic evaluations.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	46	53
Week 4 (Day 28) (N=46, 52)	2.60 (1.68)	1.71 (1.45)
Week 8 (Day 56) (N= 42, 53)	3.33 (3.71)	1.72 (3.32)

9. Secondary Outcome

Title	Change From Baseline to Week 8 in Plasma Renin Activity (PRA)
Description	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.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): consisted of all randomized patients. Mis-randomized patients were excluded from the FAS. Patients with both baseline and week 8 measurement for PRA are included in this analysis.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	42	47
Mean (Standard Deviation) [ng/mL/hr]	-0.519 (1.4016)	-1.962 (6.7419)

10. Secondary Outcome

Title	Change From Baseline to Week 8 in Plasma Renin Concentration (PRC)
Description	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.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): consisted of all randomized patients. Mis-randomized patients were excluded from the FAS. Patients with both baseline and week 8 measurement for PRC are included in this analysis.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	42	47
Mean (Standard Deviation) [ng/L]	37.881 (63.4412)	50.967 (81.8987)

11. Secondary Outcome

Title	Number of Patients With Adverse Events, Serious Adverse Events and Death
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.

Arm/Group Title	Aliskiren: Fed	Aliskiren: Fasting
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg once daily taken after after an overnight fast
Measure Participants	295	294
Any Adverse event	73	90
Serious Adverse events	4	2
Death	0	0

Adverse Events

Adverse Event Reporting Description	Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.
Arm/Group Title	Aliskiren: Fed		Aliskiren 300 mg (Fasted)
Arm/Group Description	Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast		Aliskiren 300 mg once daily taken after after an overnight fast
All Cause Mortality
	Aliskiren: Fed		Aliskiren 300 mg (Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren: Fed		Aliskiren 300 mg (Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/295 (1.4%)		2/294 (0.7%)
Cardiac disorders
Coronary artery stenosis	0/295 (0%)		1/294 (0.3%)
Gastrointestinal disorders
Gastritis	1/295 (0.3%)		0/294 (0%)
Infections and infestations
Staphylococcal infection	1/295 (0.3%)		0/294 (0%)
Injury, poisoning and procedural complications
Overdose	1/295 (0.3%)		0/294 (0%)
Wrist fracture	0/295 (0%)		1/294 (0.3%)
Vascular disorders
Hypertension	1/295 (0.3%)		0/294 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren: Fed		Aliskiren 300 mg (Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/295 (1%)		16/294 (5.4%)
Gastrointestinal disorders
Diarrhoea	3/295 (1%)		16/294 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 or disclosure of trial results in their entirety.