Trial Outcomes & Findings for 8-week Randomized, Open-label Study to Evaluate Food Effect on Efficacy and Safety of Oral Aliskiren 300 mg in Patients With Hypertension (NCT NCT01570686)

NCT ID: NCT01570686

Last Updated: 2014-01-22

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 589 participants
• Primary outcome timeframe: Baseline, week 8
• Results posted on: 2014-01-22

Participant Flow

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.

Participant milestones

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

Reasons for withdrawal

Measure	Aliskiren: Fed Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting Aliskiren 300 mg once daily taken after after an overnight fast
Overall Study Abnormal test procedure result(s)	1	1
Overall Study Administrative problems	0	1
Overall Study Adverse Event	8	6
Overall Study Lost to Follow-up	4	3
Overall Study Protocol Deviation	3	0
Overall Study Withdrawal by Subject	4	4
Overall Study Unsatisfactory therapeutic effect	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Aliskiren: Fed n=296 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=294 Participants Aliskiren 300 mg once daily taken after after an overnight fast	Total n=590 Participants Total of all reporting groups
Age, Continuous	55.7 Years STANDARD_DEVIATION 10.44 • n=5 Participants	56.1 Years STANDARD_DEVIATION 11.03 • n=7 Participants	55.9 Years STANDARD_DEVIATION 10.73 • n=5 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	126 Participants n=7 Participants	278 Participants n=5 Participants
Sex: Female, Male Male	144 Participants n=5 Participants	168 Participants n=7 Participants	312 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, week 8

Population: 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.

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.

Outcome measures

Measure	Aliskiren: Fed n=263 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=266 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Systolic Blood Pressure (maSBP)	-7.03 mmHg Standard Error 0.50	-7.79 mmHg Standard Error 0.50

SECONDARY outcome

Timeframe: Baseline, week 8

Population: 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.

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.

Outcome measures

Measure	Aliskiren: Fed n=263 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=266 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Change From Baseline (Visit 3) to End of Study (Week 8) in Mean 24 Hour Ambulatory Diastolic Blood Pressure (maDBP)	-4.01 mmHg Standard Error 0.31	-4.39 mmHg Standard Error 0.31

SECONDARY outcome

Timeframe: 8 weeks

Population: 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.

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

Outcome measures

Measure	Aliskiren: Fed n=293 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=294 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Percentage of Patients Achieving Blood Pressure Control	44.7 Percentage of patients	41.5 Percentage of patients

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: 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.

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.

Outcome measures

Measure	Aliskiren: Fed n=293 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=294 Participants Aliskiren 300 mg once daily taken after after an overnight fast
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) Mean sitting SBP (msSBP)	-13.65 mmHg Standard Error 0.85	-13.98 mmHg Standard Error 0.85
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) Mean sitting DBP (msDBP)	-8.97 mmHg Standard Error 0.50	-8.56 mmHg Standard Error 0.50

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: 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.

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.

Outcome measures

Measure	Aliskiren: Fed n=293 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=294 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Percentage of Patients Achieving a Successful Response in Systolic Blood Pressure Reduction	54.9 Percentage of patients	55.8 Percentage of patients

SECONDARY outcome

Timeframe: 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)

Population: 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

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

Outcome measures

Measure	Aliskiren: Fed n=46 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=53 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Pharmacokinetic (PK) of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration in Fasted vs. Fed Week 4 (Day 28) (N= 46, 52)	108 ng/mL Standard Deviation 153	273 ng/mL Standard Deviation 276
Pharmacokinetic (PK) of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration in Fasted vs. Fed Week 8 (Day 56) (N= 42, 53)	102 ng/mL Standard Deviation 139	252 ng/mL Standard Deviation 220

SECONDARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

Measure	Aliskiren: Fed n=46 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=53 Participants Aliskiren 300 mg once daily taken after after an overnight fast
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 (Day 28) (N= 44, 50)	872 ng*h/mL Standard Deviation 603	1580 ng*h/mL Standard Deviation 1120
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 8 (Day 56) (N= 40, 51)	1100 ng*h/mL Standard Deviation 1620	1540 ng*h/mL Standard Deviation 1120

SECONDARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

Measure	Aliskiren: Fed n=46 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=53 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration in Fasted vs. Fed Week 4 (Day 28) (N=46, 52)	2.60 Hour Standard Deviation 1.68	1.71 Hour Standard Deviation 1.45
Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration in Fasted vs. Fed Week 8 (Day 56) (N= 42, 53)	3.33 Hour Standard Deviation 3.71	1.72 Hour Standard Deviation 3.32

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: 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.

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.

Outcome measures

Measure	Aliskiren: Fed n=42 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=47 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Change From Baseline to Week 8 in Plasma Renin Activity (PRA)	-0.519 ng/mL/hr Standard Deviation 1.4016	-1.962 ng/mL/hr Standard Deviation 6.7419

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: 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.

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.

Outcome measures

Measure	Aliskiren: Fed n=42 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=47 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Change From Baseline to Week 8 in Plasma Renin Concentration (PRC)	37.881 ng/L Standard Deviation 63.4412	50.967 ng/L Standard Deviation 81.8987

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	Aliskiren: Fed n=295 Participants Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren: Fasting n=294 Participants Aliskiren 300 mg once daily taken after after an overnight fast
Number of Patients With Adverse Events, Serious Adverse Events and Death Any Adverse event	73 Patients	90 Patients
Number of Patients With Adverse Events, Serious Adverse Events and Death Serious Adverse events	4 Patients	2 Patients
Number of Patients With Adverse Events, Serious Adverse Events and Death Death	0 Patients	0 Patients

Adverse Events

Aliskiren: Fed

Serious events: 4 serious events

Other events: 3 other events

Deaths: 0 deaths

Aliskiren 300 mg (Fasted)

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aliskiren: Fed n=295 participants at risk Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg (Fasted) n=294 participants at risk Aliskiren 300 mg once daily taken after after an overnight fast
Cardiac disorders Coronary artery stenosis	0.00% 0/295 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.	0.34% 1/294 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.
Gastrointestinal disorders Gastritis	0.34% 1/295 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.	0.00% 0/294 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.
Infections and infestations Staphylococcal infection	0.34% 1/295 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.	0.00% 0/294 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.
Injury, poisoning and procedural complications Overdose	0.34% 1/295 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.	0.00% 0/294 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/295 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.	0.34% 1/294 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.
Vascular disorders Hypertension	0.34% 1/295 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.	0.00% 0/294 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.

Other adverse events

Measure	Aliskiren: Fed n=295 participants at risk Aliskiren 300 mg once daily, taken 30 minutes after start of light breakfast	Aliskiren 300 mg (Fasted) n=294 participants at risk Aliskiren 300 mg once daily taken after after an overnight fast
Gastrointestinal disorders Diarrhoea	1.0% 3/295 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.	5.4% 16/294 Safety Set (SAF): consisted of all patients who received at least one dose of randomized study medication.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: trialandresults.registries@novartis.com

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 or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER