Trial Outcomes & Findings for Safety and Tolerability and Efficacy of LCZ696 in Japanese Hypertensive Patients With Renal Dysfunction (NCT NCT01593787)

NCT ID: NCT01593787

Last Updated: 2015-08-13

Results Overview

Percentage of patients with total adverse events, serious adverse events and death were reported.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 32 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2015-08-13

Participant Flow

Participant milestones

Measure	LCZ696 100 mg All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.
Overall Study STARTED	6	8	18
Overall Study COMPLETED	5	8	18
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Measure	LCZ696 100 mg All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.
Overall Study Adverse Event	1	0	0

Baseline Characteristics

Safety and Tolerability and Efficacy of LCZ696 in Japanese Hypertensive Patients With Renal Dysfunction

Baseline characteristics by cohort

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total n=32 Participants Total of all reporting groups
Age, Continuous	69.0 Years STANDARD_DEVIATION 5.10 • n=5 Participants	71.3 Years STANDARD_DEVIATION 8.80 • n=7 Participants	62.3 Years STANDARD_DEVIATION 9.04 • n=5 Participants	65.8 Years STANDARD_DEVIATION 9.12 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants	24 Participants n=4 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: Safety Set: This set included all participants who received at least one dose of LCZ696. AE analysis was determined by actual treatment, i.e. the LCZ696 dose on the day in which the corresponding summary was targeting. Other safety analysis was determined by the maximum treatment.

Percentage of patients with total adverse events, serious adverse events and death were reported.

Outcome measures

Measure	LCZ696 100 mg n=32 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=26 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) Adverse events (serious and non-serious)	31.3 Percentage of participants	0 Percentage of participants	27.8 Percentage of participants	43.8 Percentage of participants
Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) Serious Adverse Events	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) Deaths	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: Full Analysis Set (FAS): This set included all participants who entered the treatment epoch. Patients who were not qualified to enter the treatment epoch were excluded from the FAS provided those participants did not receive LCZ696.

Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurements.

Outcome measures

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 8	-19.71 mmHg Standard Deviation 12.314	-27.19 mmHg Standard Deviation 10.557	-17.79 mmHg Standard Deviation 10.701	-20.50 mmHg Standard Deviation 11.329

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: FAS

Outcome measures

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8	-7.17 mmHg Standard Deviation 4.690	-9.94 mmHg Standard Deviation 7.557	-7.99 mmHg Standard Deviation 6.385	-8.32 mmHg Standard Deviation 6.308

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

A successful BP control was defined as msSBP <130 mmHg and msDBP <80 mmHg

Outcome measures

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Percentage of Participants Achieving a Successful BP Control at Week 8	66.7 Percentage of Participants	37.5 Percentage of Participants	5.6 Percentage of Participants	25.0 Percentage of Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

SBP control was defined as msSBP <130 mmHg.

Outcome measures

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Percentage of Participants Achieving SBP Control at Week 8	66.7 Percentage of participants	50.0 Percentage of participants	44.4 Percentage of participants	50.0 Percentage of participants

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

DBP control was defined as msDBP <80 mmHg.

Outcome measures

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Percentage of Participants Achieving DBP Control at Week 8	83.3 Percentage of participants	62.5 Percentage of participants	27.8 Percentage of participants	46.9 Percentage of participants

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

Successful response rate was defined as msSBP <130 mmHg or a reduction of ≥20 mmHg from baseline

Outcome measures

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Percentage of Participants Achieving a Successful Response Rate in msSBP at Week 8	66.7 Percentage of participants	75.0 Percentage of participants	50.0 Percentage of participants	59.4 Percentage of participants

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

Successful response rate was defined as msDBP <80 mmHg or a reduction of ≥10 mmHg from baseline.

Outcome measures

Measure	LCZ696 100 mg n=6 Participants All participants were started on LCZ696 100 mg once daily on day 1.	LCZ696 200 mg n=8 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg.	LCZ696 400 mg n=18 Participants All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg.	Total LCZ696 n=32 Participants All participants who received LCZ696
Percentage of Participants Achieving a Successful Response Rate in msDBP at Week 8	83.3 Percentage of participants	87.5 Percentage of participants	61.1 Percentage of participants	71.9 Percentage of participants

Adverse Events

LCZ 100 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

LCZ 400 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Total LCZ696

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

LCZ 200 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	LCZ 100 mg n=32 participants at risk LCZ 100 mg	LCZ 400 mg n=18 participants at risk LCZ 400 mg	Total LCZ696 n=32 participants at risk All participants who received LCZ696	LCZ 200 mg n=26 participants at risk LCZ 200 mg
Cardiac disorders SUPRAVENTRICULAR EXTRASYSTOLES	0.00% 0/32	5.6% 1/18	3.1% 1/32	0.00% 0/26
Gastrointestinal disorders DYSPEPSIA	0.00% 0/32	5.6% 1/18	3.1% 1/32	0.00% 0/26
Gastrointestinal disorders TOOTHACHE	0.00% 0/32	5.6% 1/18	3.1% 1/32	0.00% 0/26
Infections and infestations NASOPHARYNGITIS	15.6% 5/32	5.6% 1/18	18.8% 6/32	0.00% 0/26
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/32	5.6% 1/18	3.1% 1/32	0.00% 0/26
Skin and subcutaneous tissue disorders PRURITUS	0.00% 0/32	5.6% 1/18	3.1% 1/32	0.00% 0/26

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 (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