Trial Outcomes & Findings for Assessment of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension (NCT NCT01681576)
NCT ID: NCT01681576
Last Updated: 2015-11-10
Results Overview
Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
72 participants
Primary outcome timeframe
0-6 and 0-24 hours on Day 1
Results posted on
2015-11-10
Participant Flow
Period 1: 4 weeks treatment with LCZ696 400mg QD or Valsartan 320mg, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with Valsartan 320mg QD or LCZ696 400mg QD
Participant milestones
| Measure |
LCZ696 Followed by Valsartan
Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks
|
Valsartan Followed by LCZ696
Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks
|
|---|---|---|
|
Period 1
STARTED
|
36
|
36
|
|
Period 1
COMPLETED
|
34
|
36
|
|
Period 1
NOT COMPLETED
|
2
|
0
|
|
Period 2
STARTED
|
34
|
36
|
|
Period 2
COMPLETED
|
30
|
35
|
|
Period 2
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
LCZ696 Followed by Valsartan
Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks
|
Valsartan Followed by LCZ696
Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks
|
|---|---|---|
|
Period 1
Adverse Event
|
1
|
0
|
|
Period 1
Protocol Deviation
|
1
|
0
|
|
Period 2
subject/guardian decision
|
3
|
1
|
|
Period 2
Non-compliance with study treatment
|
1
|
0
|
Baseline Characteristics
Assessment of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension
Baseline characteristics by cohort
| Measure |
LCZ696 Followed by Valsartan
n=36 Participants
Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks
|
Valsartan 320mg
n=36 Participants
Period 1: 4 weeks treatment with Valsartan 320mg QD, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with LCZ696 400mg QD
|
Total
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.7 years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
58.9 years
STANDARD_DEVIATION 7.5 • n=7 Participants
|
57.3 years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0-6 and 0-24 hours on Day 1Population: Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1
Outcome measures
| Measure |
LCZ696 - ALL
n=70 Participants
LCZ696 400mg QD
|
Valsartan -ALL
n=67 Participants
Valsartan 320mg QD
|
|---|---|---|
|
Cumulative Sodium Excretion (Natriuresis) at Day 1
0-6h (n=69,66)
|
61.26 mmol
Standard Deviation 31.167
|
37.13 mmol
Standard Deviation 20.761
|
|
Cumulative Sodium Excretion (Natriuresis) at Day 1
0-24h (n=69,66)
|
188.87 mmol
Standard Deviation 74.458
|
138.92 mmol
Standard Deviation 58.905
|
SECONDARY outcome
Timeframe: 0-6 and 0-24 hours on Day 28Population: Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 28
Outcome measures
| Measure |
LCZ696 - ALL
n=70 Participants
LCZ696 400mg QD
|
Valsartan -ALL
n=67 Participants
Valsartan 320mg QD
|
|---|---|---|
|
Cumulative Sodium Excretion (Natriuresis) at Day 28
0-6h (n=69,66)
|
39.30 mmol
Standard Deviation 18.841
|
44.57 mmol
Standard Deviation 23.479
|
|
Cumulative Sodium Excretion (Natriuresis) at Day 28
0-24h (n=69,66)
|
144.71 mmol
Standard Deviation 51.094
|
153.82 mmol
Standard Deviation 62.449
|
SECONDARY outcome
Timeframe: Day -1, Day 1 & Day 28Population: Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
Urine will be collected and volume measured in fractions of 0 to 6 hours and 0 to 24 hours Day-1, Day 1 and Day 28
Outcome measures
| Measure |
LCZ696 - ALL
n=70 Participants
LCZ696 400mg QD
|
Valsartan -ALL
n=67 Participants
Valsartan 320mg QD
|
|---|---|---|
|
Urine Volume (Diuresis) Over Time
Day -1 0-6h (n=70,67)
|
855.1 mL
Standard Deviation 450.28
|
806.2 mL
Standard Deviation 462.20
|
|
Urine Volume (Diuresis) Over Time
Day -1 0-24h (n=70,67)
|
2752.8 mL
Standard Deviation 722.53
|
2756.2 mL
Standard Deviation 1010.86
|
|
Urine Volume (Diuresis) Over Time
Day 1 0-6h (n=70,67)
|
1215.9 mL
Standard Deviation 475.57
|
923.0 mL
Standard Deviation 443.65
|
|
Urine Volume (Diuresis) Over Time
Day 1 0-24h (n=70,67)
|
3172.3 mL
Standard Deviation 957.70
|
2813.8 mL
Standard Deviation 930.05
|
|
Urine Volume (Diuresis) Over Time
Day 28 0-6h (n=69,66)
|
948.8 mL
Standard Deviation 415.14
|
1042.7 mL
Standard Deviation 530.15
|
|
Urine Volume (Diuresis) Over Time
Day 28 0-24h (n=69,66)
|
2820.0 mL
Standard Deviation 847.81
|
3000.2 mL
Standard Deviation 1139.75
|
SECONDARY outcome
Timeframe: Day-1, Day 14 and Day 28Population: Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
Seated Office BP (systolic blood pressure (SBP) and diastolic blood pressure (DBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.
Outcome measures
| Measure |
LCZ696 - ALL
n=70 Participants
LCZ696 400mg QD
|
Valsartan -ALL
n=67 Participants
Valsartan 320mg QD
|
|---|---|---|
|
Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
Day -1 Sitting SBP (n=70,67)
|
140.20 mmHg
Standard Deviation 13.691
|
137.85 mmHg
Standard Deviation 12.703
|
|
Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
Day 28 Sitting SBP (n=69,66)
|
127.01 mmHg
Standard Deviation 12.723
|
132.07 mmHg
Standard Deviation 15.195
|
|
Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
Day 14 Sitting DBP (n=69,66)
|
80.43 mmHg
Standard Deviation 7.808
|
80.57 mmHg
Standard Deviation 9.246
|
|
Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
Day 28 Sitting DBP (n=69,66)
|
80.44 mmHg
Standard Deviation 7.840
|
81.40 mmHg
Standard Deviation 9.276
|
|
Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
Day 14 Sitting SBP (n=69,66)
|
126.88 mmHg
Standard Deviation 12.451
|
129.23 mmHg
Standard Deviation 12.784
|
|
Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
Day -1 Sitting DBP (n=70,67)
|
86.63 mmHg
Standard Deviation 8.955
|
85.59 mmHg
Standard Deviation 9.299
|
SECONDARY outcome
Timeframe: Day-1, Day 14 and Day 28Population: Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements
Outcome measures
| Measure |
LCZ696 - ALL
n=70 Participants
LCZ696 400mg QD
|
Valsartan -ALL
n=67 Participants
Valsartan 320mg QD
|
|---|---|---|
|
Mean Sitting Pulse Pressure (PP) Over Time
Day -1 Sitting mean PP (n=70,67)
|
63.91 mmHg
Standard Deviation 8.392
|
64.92 mmHg
Standard Deviation 10.086
|
|
Mean Sitting Pulse Pressure (PP) Over Time
Day 14 Sitting mean PP (n=69,66)
|
71.91 mmHg
Standard Deviation 10.370
|
69.61 mmHg
Standard Deviation 8.888
|
|
Mean Sitting Pulse Pressure (PP) Over Time
Day 28 Sitting mean PP (n=69,66)
|
65.21 mmHg
Standard Deviation 8.999
|
63.63 mmHg
Standard Deviation 8.843
|
Adverse Events
LCZ696 400 mg QD
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Valsartan 320 mg QD
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LCZ696 400 mg QD
n=71 participants at risk
LCZ696 400 mg QD
|
Valsartan 320 mg QD
n=67 participants at risk
Valsartan 320 mg QD
|
|---|---|---|
|
Gastrointestinal disorders
DRY MOUTH
|
2.8%
2/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
0.00%
0/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Infections and infestations
NASOPHARYNGITIS
|
2.8%
2/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
6.0%
4/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
3.0%
2/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Musculoskeletal and connective tissue disorders
FLANK PAIN
|
0.00%
0/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
3.0%
2/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Nervous system disorders
DIZZINESS
|
7.0%
5/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
7.5%
5/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Nervous system disorders
HEADACHE
|
1.4%
1/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
6.0%
4/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Renal and urinary disorders
HAEMATURIA
|
4.2%
3/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
3.0%
2/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Renal and urinary disorders
PYURIA
|
2.8%
2/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
0.00%
0/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
5.6%
4/71
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
0.00%
0/67
Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.
|
Additional Information
Study Director
Novartis
Phone: 862-778-8300
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