Trial Outcomes & Findings for To Study the Effects of Aliskiren on Albuminuria and Various Biomarkers in Patients With Nephropathy (NCT NCT01302899)
NCT ID: NCT01302899
Last Updated: 2013-01-30
Results Overview
Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.
TERMINATED
PHASE2
8 participants
26 weeks
2013-01-30
Participant Flow
Participant milestones
| Measure |
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)+HCTZ/Ram+Ali/Ram
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
|
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)/Ram+Ali + HCTZ/Ram
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule placebo to HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
|
|---|---|---|
|
Period 1 (Day 1 to End of Week 6)
STARTED
|
4
|
4
|
|
Period 1 (Day 1 to End of Week 6)
COMPLETED
|
4
|
4
|
|
Period 1 (Day 1 to End of Week 6)
NOT COMPLETED
|
0
|
0
|
|
Period 2 (Weeks 7 to 12)
STARTED
|
4
|
4
|
|
Period 2 (Weeks 7 to 12)
COMPLETED
|
3
|
3
|
|
Period 2 (Weeks 7 to 12)
NOT COMPLETED
|
1
|
1
|
|
Period 3 (Weeks 13 to 18)
STARTED
|
3
|
3
|
|
Period 3 (Weeks 13 to 18)
COMPLETED
|
3
|
3
|
|
Period 3 (Weeks 13 to 18)
NOT COMPLETED
|
0
|
0
|
|
Period 4 (Weeks 19 to 26)
STARTED
|
3
|
3
|
|
Period 4 (Weeks 19 to 26)
COMPLETED
|
3
|
3
|
|
Period 4 (Weeks 19 to 26)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)+HCTZ/Ram+Ali/Ram
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
|
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)/Ram+Ali + HCTZ/Ram
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule placebo to HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
|
|---|---|---|
|
Period 2 (Weeks 7 to 12)
Protocol Deviation
|
1
|
0
|
|
Period 2 (Weeks 7 to 12)
Abnormal laboratory value(s)
|
0
|
1
|
Baseline Characteristics
To Study the Effects of Aliskiren on Albuminuria and Various Biomarkers in Patients With Nephropathy
Baseline characteristics by cohort
| Measure |
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)+HCTZ/Ram+Ali/Ram
n=4 Participants
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
|
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)/Ram+Ali + HCTZ/Ram
n=4 Participants
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule placebo to HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
50.5 years
STANDARD_DEVIATION 6.76 • n=5 Participants
|
58.5 years
STANDARD_DEVIATION 8.70 • n=7 Participants
|
54.5 years
STANDARD_DEVIATION 8.38 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Systolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msSBP was calculated. All BP measurements were to be performed on the same arm.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Diastolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msDBP was calculated. All BP measurements were to be performed on the same arm.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
All patients had to visit the main center for renal function measurements. The measurements were performed using the constant infusion method with I-iothalamate (IOT) and I-hippuran. GFR was calculated as the urinary clearance of IOT.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: The study was terminated and consequentially was underpowered for adequate statistical analysis
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to week 26Population: The study was terminated and consequentially was underpowered for adequate statistical analysis
Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. Plasma PRA is a direct measure of the formation of Ang I in the plasma.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to week 26Population: The study was terminated and consequentially was underpowered for adequate statistical analysis
Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. PRC measures the concentration of immunoactive renin in the plasma.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: The safety analysis set consisted of all patients who received at least one study drug and had no major protocol deviations that could have impacted safety data.
Outcome measures
| Measure |
Ramipril +HCTZ
n=8 Participants
All patients were treated for 6 weeks with daily doses of ramipril 10 mg + placebo to 2 x 150 mg aliskiren (300 mg) + HCTZ 25 mg
|
Ramipril+Aliskiren + HCTZ
n=7 Participants
All patients were treated for 6 weeks with daily doses of ramipril 10 mg + aliskiren 300 mg\* (2 x 150 mg) + HCTZ 25 mg
\* Patients were started on aliskiren 150 mg for the 1st week and up-titrated to 300 mg (2 x 150 mg) at the beginning of the 2nd week and continued on this dose until the end of the 6th week of the period
|
Ramipril+Aliskiren
n=7 Participants
All patients were treated for 6 weeks with daily doses of ramipril 10 mg + aliskiren 300 mg\* (2 tablets of 150 mg) + placebo to 25 mg HCTZ
\*Patients were started on aliskiren 150 mg for the 1st week and up-titrated to 300 mg (2 x 150 mg) at the beginning of the 2nd week and continued on this dose until the end of the 6th week of the period
|
Ramipril
n=6 Participants
All patients were treated for 8 weeks with daily doses of ramipril 10 mg + placebo to 2 x 150 mg aliskiren + placebo to 25 mg HCTZ
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death as Assessment of Safety and Tolerability of Aliskiren Added to Ramipril
patients with adverse events
|
7 Participants
|
5 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death as Assessment of Safety and Tolerability of Aliskiren Added to Ramipril
patients with serious adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death as Assessment of Safety and Tolerability of Aliskiren Added to Ramipril
patients with death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Ramipril +HCTZ
Ramipril+Aliskiren + HCTZ
Ramipril+Aliskiren
Ramipril
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ramipril +HCTZ
n=8 participants at risk
All patients were treated for 6 weeks with daily doses of ramipril 10 mg + placebo to 2 x 150 mg aliskiren (300 mg) + HCTZ 25 mg
|
Ramipril+Aliskiren + HCTZ
n=7 participants at risk
All patients were treated for 6 weeks with daily doses of ramipril 10 mg + aliskiren 300 mg\* (2 x 150 mg) + HCTZ 25 mg
\* Patients were started on aliskiren 150 mg for the 1st week and up-titrated to 300 mg (2 x 150 mg) at the beginning of the 2nd week and continued on this dose until the end of the 6th week of the period
|
Ramipril+Aliskiren
n=7 participants at risk
All patients were treated for 6 weeks with daily doses of ramipril 10 mg + aliskiren 300 mg\* (2 tablets of 150 mg) + placebo to 25 mg HCTZ
\*Patients were started on aliskiren 150 mg for the 1st week and up-titrated to 300 mg (2 x 150 mg) at the beginning of the 2nd week and continued on this dose until the end of the 6th week of the period
|
Ramipril
n=6 participants at risk
All patients were treated for 8 weeks with daily doses of ramipril 10 mg + placebo to 2 x 150 mg aliskiren + placebo to 25 mg HCTZ
|
|---|---|---|---|---|
|
General disorders
Fatigue
|
37.5%
3/8
|
28.6%
2/7
|
28.6%
2/7
|
33.3%
2/6
|
|
Nervous system disorders
Dizziness
|
50.0%
4/8
|
28.6%
2/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
37.5%
3/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Orthostatic intolerance
|
0.00%
0/8
|
28.6%
2/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Nervous system disorders
Headache
|
25.0%
2/8
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Infections and infestations
Nasopharyngitis
|
12.5%
1/8
|
14.3%
1/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
25.0%
2/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Edema peripheral
|
12.5%
1/8
|
0.00%
0/7
|
0.00%
0/7
|
33.3%
2/6
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
1/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Angina pectoris
|
12.5%
1/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
1/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Blood pressure increased
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/8
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhea
|
12.5%
1/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/8
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Vascular disorders
Hypotension
|
0.00%
0/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Nocturia
|
12.5%
1/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Palpitations
|
12.5%
1/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Renal function test abnormal
|
0.00%
0/8
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Salt craving
|
0.00%
0/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Snoring
|
0.00%
0/8
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Nervous system disorders
Tension headache
|
12.5%
1/8
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Eye disorders
Vision blurred
|
0.00%
0/8
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
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 or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER