Trial Outcomes & Findings for A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus (NCT NCT00660309)
NCT ID: NCT00660309
Last Updated: 2012-08-29
Results Overview
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.
COMPLETED
PHASE4
45 participants
Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.
2012-08-29
Participant Flow
Participant milestones
| Measure |
Aliskiren
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
22
|
|
Overall Study
Treated With Aliskiren or Irbesartan
|
22
|
21
|
|
Overall Study
Pharmacodynamic Analysis Set
|
22
|
20
|
|
Overall Study
COMPLETED
|
21
|
19
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Aliskiren
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
3
|
Baseline Characteristics
A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Aliskiren
n=23 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
56.5 years
STANDARD_DEVIATION 11.20 • n=5 Participants
|
57.7 years
STANDARD_DEVIATION 8.14 • n=7 Participants
|
57.1 years
STANDARD_DEVIATION 9.73 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan
|
37.18 mL/min/1.73m^2
Standard Deviation 36.19
|
35.88 mL/min/1.73m^2
Standard Deviation 35.53
|
PRIMARY outcome
Timeframe: Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This multiple dose effect at steady state (MDE\_SS) was calculated as Day 15 baseline - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values.
Outcome measures
| Measure |
Aliskiren
n=21 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=18 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline to Steady State Trough in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
|
-5.67 mL/min/1.73m^2
Standard Deviation 49.10
|
-13.08 mL/min/1.73m^2
Standard Deviation 27.01
|
PRIMARY outcome
Timeframe: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This maximum multiple dose effect (MDE\_Max) was calculated as Day 15 peak - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=21 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=18 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
|
24.62 mL/min/1.73m^2
Standard Deviation 52.93
|
24.22 mL/min/1.73m^2
Standard Deviation 38.23
|
PRIMARY outcome
Timeframe: Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) was calculated as Day 15 peak - Day 2 peak. Peak RPF was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=21 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=18 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Single Dose Peak to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
|
-12.74 mL/min/1.73m^2
Standard Deviation 37.05
|
-14.67 mL/min/1.73m^2
Standard Deviation 35.75
|
SECONDARY outcome
Timeframe: Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril
|
43.32 mL/min/1.73m^2
Standard Deviation 42.78
|
40.13 mL/min/1.73m^2
Standard Deviation 31.70
|
SECONDARY outcome
Timeframe: Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=16 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril
|
11.29 mL/min/1.73m^2
Standard Deviation 15.33
|
7.41 mL/min/1.73m^2
Standard Deviation 12.39
|
SECONDARY outcome
Timeframe: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=16 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan
|
10.52 mL/min/1.73m^2
Standard Deviation 11.22
|
10.16 mL/min/1.73m^2
Standard Deviation 10.10
|
SECONDARY outcome
Timeframe: Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. This multiple dose effect at steady state (MDE\_SS) was calculated as Day 15 baseline - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values.
Outcome measures
| Measure |
Aliskiren
n=21 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=15 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline to Steady State Trough in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
|
1.05 mL/min/1.73m^2
Standard Deviation 10.24
|
-5.67 mL/min/1.73m^2
Standard Deviation 10.00
|
SECONDARY outcome
Timeframe: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. This maximum multiple dose effect (MDE\_Max) was calculated as Day 15 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=21 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=14 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
|
8.69 mL/min/1.73m^2
Standard Deviation 9.61
|
2.96 mL/min/1.73m^2
Standard Deviation 6.98
|
SECONDARY outcome
Timeframe: Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.Population: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data. Analysis includes patients for whom data were available.
Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) was calculated as Day 15 peak - Day 2 peak GFR. Peak GFR was obtained using a moving average concept.
Outcome measures
| Measure |
Aliskiren
n=21 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=14 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Single Dose Peak to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
|
-1.71 mL/min/1.73m^2
Standard Deviation 9.38
|
-8.68 mL/min/1.73m^2
Standard Deviation 7.05
|
SECONDARY outcome
Timeframe: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.Population: PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' \[Aliskiren, Irbesartan\].
The following plasma renin concentration effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE\_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE\_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) = Day 15, 5 hour / Day 2, 5 hour.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan
SDE after captopril [N=22, 20]
|
1.18 ratio
Interval 0.95 to 1.48
|
0.92 ratio
Interval 0.77 to 1.09
|
|
Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan
SDE after aliskiren/irbesartan [N=22, 20]
|
2.53 ratio
Interval 2.09 to 3.06
|
1.04 ratio
Interval 0.92 to 1.16
|
|
Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan
Steady State Trough Effect [N= 21, 19]
|
4.41 ratio
Interval 3.0 to 6.48
|
2.35 ratio
Interval 1.48 to 3.73
|
|
Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan
Steady State Peak Effect [N=21, 19]
|
4.81 ratio
Interval 3.46 to 6.68
|
2.06 ratio
Interval 1.36 to 3.12
|
|
Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan
Accumulation of Peak Effect [N= 21, 18]
|
1.93 ratio
Interval 1.34 to 2.76
|
1.91 ratio
Interval 1.23 to 2.97
|
SECONDARY outcome
Timeframe: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.Population: PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' \[Aliskiren, Irbesartan\].
The following plasma pro-renin concentration effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE\_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE\_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) = Day 15, 5 hour / Day 2, 5 hour.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan
SDE after captopril [N=22, 20]
|
0.97 ratio
Interval 0.91 to 1.03
|
1.01 ratio
Interval 0.97 to 1.05
|
|
Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan
SDE after aliskiren/irbesartan [N=22, 20]
|
0.93 ratio
Interval 0.89 to 0.98
|
0.96 ratio
Interval 0.86 to 1.08
|
|
Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan
Steady State Trough Effect [N= 21, 19]
|
1.07 ratio
Interval 0.89 to 1.28
|
1.20 ratio
Interval 0.98 to 1.47
|
|
Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan
Steady State Peak Effect [N=21, 19]
|
1.10 ratio
Interval 0.99 to 1.23
|
1.13 ratio
Interval 0.9 to 1.43
|
|
Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan
Accumulation of Peak Effect [N= 21, 18]
|
1.17 ratio
Interval 1.05 to 1.32
|
1.18 ratio
Interval 0.93 to 1.49
|
SECONDARY outcome
Timeframe: Predose and 5 hours post dose on Days 1, 2 and 15.Population: PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' \[Aliskiren, Irbesartan\].
PRA was measured by the trapping method and the following effects assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 baseline. Steady state trough effect (multiple dose effect at steady state; MDE\_SS) = Day 15 baseline / Day 2 baseline. Steady State peak effect (maximum multiple dose effect; MDE\_Max) = Day 15, 5 hour / Day 2 baseline. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) = Day 15, 5 hour / Day 2, 5 hour.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan
Steady State Peak Effect [N=21, 18]
|
0.07 ratio
Interval 0.04 to 0.13
|
3.28 ratio
Interval 1.67 to 6.46
|
|
Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan
SDE after captopril [N=22, 20]
|
1.47 ratio
Interval 1.16 to 1.84
|
1.19 ratio
Interval 0.83 to 1.69
|
|
Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan
SDE after aliskiren/irbesartan [N=22, 20]
|
0.09 ratio
Interval 0.05 to 0.15
|
1.30 ratio
Interval 0.92 to 1.82
|
|
Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan
Steady State Trough Effect [N= 21, 19]
|
0.12 ratio
Interval 0.07 to 0.21
|
3.79 ratio
Interval 1.77 to 8.12
|
|
Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan
Accumulation of Peak Effect [N= 21, 18]
|
0.95 ratio
Interval 0.83 to 1.09
|
2.67 ratio
Interval 1.21 to 5.91
|
SECONDARY outcome
Timeframe: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.Population: PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' \[Aliskiren, Irbesartan\].
The following angiotensin I effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE\_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE\_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) = Day 15, 5 hour / Day 2, 5 hour.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan
SDE after aliskiren/irbesartan [N=22, 20]
|
0.14 ratio
Interval 0.09 to 0.25
|
0.83 ratio
Interval 0.57 to 1.22
|
|
Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan
Steady State Trough Effect [N= 21, 19]
|
0.24 ratio
Interval 0.12 to 0.47
|
2.67 ratio
Interval 1.2 to 5.93
|
|
Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan
Steady State Peak Effect [N=21, 18]
|
0.14 ratio
Interval 0.07 to 0.27
|
2.21 ratio
Interval 0.96 to 5.05
|
|
Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan
Accumulation of Peak Effect [N= 21, 18]
|
1.06 ratio
Interval 0.63 to 1.8
|
2.71 ratio
Interval 1.37 to 5.36
|
|
Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan
SDE after captopril [N=22, 19]
|
2.20 ratio
Interval 1.57 to 3.08
|
1.54 ratio
Interval 1.08 to 2.2
|
SECONDARY outcome
Timeframe: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.Population: PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' \[Aliskiren, Irbesartan\].
The following angiotensin II effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE\_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE\_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) = Day 15, 5 hour / Day 2, 5 hour.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan
SDE after aliskiren/irbesartan [N=22, 20]
|
0.26 ratio
Interval 0.17 to 0.38
|
1.23 ratio
Interval 0.72 to 2.11
|
|
Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan
Steady State Peak Effect [N=21, 18]
|
0.17 ratio
Interval 0.1 to 0.28
|
3.05 ratio
Interval 1.39 to 6.69
|
|
Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan
SDE after captopril [N=22, 19]
|
0.31 ratio
Interval 0.2 to 0.47
|
0.34 ratio
Interval 0.22 to 0.54
|
|
Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan
Steady State Trough Effect [N= 21, 19]
|
0.43 ratio
Interval 0.28 to 0.67
|
4.05 ratio
Interval 1.77 to 9.26
|
|
Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan
Accumulation of Peak Effect [N= 21, 18]
|
0.69 ratio
Interval 0.43 to 1.12
|
2.49 ratio
Interval 1.16 to 5.32
|
SECONDARY outcome
Timeframe: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.Population: PD analysis set. The number of patients with data available included in each analysis is indicated by 'N' \[Aliskiren, Irbesartan\].
The following serum aldosterone effects were assessed: The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline. SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline. Steady state trough effect (multiple dose effect at steady state; MDE\_SS) = Day 15 Baseline / Day 2 Baseline. Steady State peak effect (maximum multiple dose effect; MDE\_Max) = Day 15, 5 hour / Day 2 Baseline. Accumulation of peak effect from single dose to multiple dose (MDE\_Acc) = Day 15, 5 hour / Day 2, 5 hour.
Outcome measures
| Measure |
Aliskiren
n=22 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=20 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan
SDE after captopril [N=22, 20]
|
0.58 ratio
Interval 0.44 to 0.76
|
0.75 ratio
Interval 0.53 to 1.05
|
|
Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan
SDE after aliskiren/irbesartan [N=22, 20]
|
0.66 ratio
Interval 0.49 to 0.87
|
0.65 ratio
Interval 0.49 to 0.87
|
|
Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan
Steady State Trough Effect [N= 21, 19]
|
0.81 ratio
Interval 0.59 to 1.11
|
0.82 ratio
Interval 0.61 to 1.1
|
|
Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan
Steady State Peak Effect [N= 21, 18]
|
0.60 ratio
Interval 0.45 to 0.79
|
0.64 ratio
Interval 0.44 to 0.92
|
|
Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan
Accumulation of Peak Effect [N= 21, 18]
|
0.93 ratio
Interval 0.75 to 1.15
|
1.02 ratio
Interval 0.81 to 1.3
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2 and Day 15.Population: PD analysis set. This assessment was only conducted at sites with available Canon Laser Blood Flowmeter. The number of patients with data available included in each analysis is indicated by 'N' \[Aliskiren, Irbesartan\].
Retinal blood flow was assessed using the laser Doppler technique. The blood flow in the superior temporal retinal artery in one of the eyes of each study participant was determined. The Single dose effect of aliskiren or irbesartan was measured as the change/difference between Day 2 and baseline measurements. The Multiple dose effect of aliskiren or irbesartan wsas measured as the change/difference between Day 15 and Day 2 measurements
Outcome measures
| Measure |
Aliskiren
n=13 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan
n=13 Participants
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|
|
Change From Baseline in Retinal Blood Flow After Aliskiren or Irbesartan
Single dose effect [N=13, 13]
|
-0.32 µL/min
Standard Deviation 1.37
|
0.43 µL/min
Standard Deviation 2.32
|
|
Change From Baseline in Retinal Blood Flow After Aliskiren or Irbesartan
Multiple dose effect [N=13, 11]
|
0.29 µL/min
Standard Deviation 1.46
|
0.35 µL/min
Standard Deviation 2.18
|
Adverse Events
Captopril 25 mg
Aliskiren 300 mg
Irbesartan 300 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Captopril 25 mg
n=45 participants at risk
On Day 1 participants received a single oral dose of 25 mg captopril.
|
Aliskiren 300 mg
n=22 participants at risk
Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
|
Irbesartan 300 mg
n=21 participants at risk
Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
|
|---|---|---|---|
|
General disorders
CHEST PAIN
|
0.00%
0/45 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
0.00%
0/22 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
9.5%
2/21 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
|
Investigations
BLOOD PRESSURE INCREASED
|
0.00%
0/45 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
9.1%
2/22 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
0.00%
0/21 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/45 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
9.1%
2/22 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
0.00%
0/21 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
|
Nervous system disorders
HEADACHE
|
4.4%
2/45 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
13.6%
3/22 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
19.0%
4/21 • Study duration (14 days) and 30-days follow-up period.
All patients that received at least one dose of study drug were included in the safety analysis set.
|
Additional Information
Study Director
Novartis Pharmaceuticals
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