Trial Outcomes & Findings for Efficacy and Safety of LCZ696 Compared to Olmesartan in Essential Hypertensive Patients Not Responsive to Olmesartan (NCT NCT01876368)

NCT ID: NCT01876368

Last Updated: 2015-12-07

Results Overview

Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The first 24-hour ABPM will be performed beginning at 24 hours prior to baseline visit and the second will be performed 24 hours prior to week 8 visit.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 376 participants
• Primary outcome timeframe: baseline, 8 weeks
• Results posted on: 2015-12-07

Participant Flow

Participant milestones

Measure	LCZ696 200 mg Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Overall Study STARTED	188	188
Overall Study Full Analysis Set (FAS)	188	187
Overall Study Safety Set (SAF)	188	187
Overall Study COMPLETED	179	175
Overall Study NOT COMPLETED	9	13

Reasons for withdrawal

Measure	LCZ696 200 mg Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Overall Study Adverse Event	2	5
Overall Study Lack of Efficacy	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Non-compliance with study treatment	0	1
Overall Study Physician Decision	0	2
Overall Study Protocol deviation	3	3
Overall Study Subject/guardian decision	3	1

Baseline Characteristics

Efficacy and Safety of LCZ696 Compared to Olmesartan in Essential Hypertensive Patients Not Responsive to Olmesartan

Baseline characteristics by cohort

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.	Total n=375 Participants Total of all reporting groups
Age, Continuous	57.1 Years STANDARD_DEVIATION 10.19 • n=5 Participants	58.0 Years STANDARD_DEVIATION 9.09 • n=7 Participants	57.6 Years STANDARD_DEVIATION 9.65 • n=5 Participants
Sex: Female, Male Female	91 Participants n=5 Participants	92 Participants n=7 Participants	183 Participants n=5 Participants
Sex: Female, Male Male	97 Participants n=5 Participants	95 Participants n=7 Participants	192 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 8 weeks

Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis

Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The first 24-hour ABPM will be performed beginning at 24 hours prior to baseline visit and the second will be performed 24 hours prior to week 8 visit.

Outcome measures

Measure	LCZ696 200 mg n=167 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=164 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Change From Baseline in 24-hour Mean Ambulatory Systolic Blood Pressure (maSBP)	-4.26 mmHg Standard Error 0.60	-1.04 mmHg Standard Error 0.61

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.

Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The 24-hour ABPM measurements are performed beginning 24 hours prior to baseline and week 8 visits.

Outcome measures

Measure	LCZ696 200 mg n=167 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=164 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (maDBP)	-2.27 mmHg Standard Error 0.39	-0.35 mmHg Standard Error 0.39

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS.

Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	-14.21 mmHg Standard Error 1.28	-10.03 mmHg Standard Error 1.29

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS.

Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	-7.52 mmHg Standard Error 0.70	-4.47 mmHg Standard Error 0.71

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS.

Mean sitting pulse pressure (msPP) will be calculated at screening through end of study at every visit. Mean sitting pulse pressure is calculated as msSBP-msDBP.

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Change From Baseline in Office Pulse Pressure	-6.67 mmHg Standard Error 0.94	-5.54 mmHg Standard Error 0.94

SECONDARY outcome

Timeframe: 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS

Successful overall blood pressure control is defined as both msSBP/msDBP <140/90 mmHg

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Number of Patients Achieving Successful Overall Blood Pressure Control	76 Participants	52 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS.

Successful mean sitting systolic blood pressure control is defined as msSBP <140 mmHg

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Number of Patients Achieving Successful Mean Sitting Systolic Blood Pressure (msSBP) Control	84 Participants	58 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS.

Successful mean sitting diastolic blood pressure control is defined as msDBP <90 mmHg

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Number of Patients Achieving Successful Mean Sitting Diastolic Blood Pressure (msDBP) Control	133 Participants	112 Participants

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS

Successful mean sitting systolic blood pressure response is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline.

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Number of Patients Achieving Successful Mean Sitting Systolic Blood Pressure (msSBP) Response	90 Participants	65 Participants

SECONDARY outcome

Timeframe: baseline, 8 weeks

Population: Full Analysis Set (FAS) - All patients who were randomized. Following the intent to treat principle, patients were analyzed according to the treatment they were assigned to at the randomization. However, patients who were not qualified for randomization and were inadvertently randomized into the study were excluded from the FAS

Successful mean sitting diastolic blood pressure response is defined as msDBP <90 mmHg or a reduction ≥10 mmHg from baseline.

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Number of Patients Achieving Successful Mean Sitting Diastolic Blood Pressure (msDBP) Response	137 Participants	115 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Safety Set (SAF) - All patients who received at least one dose of study medication in the double-blind epoch. Patients were analyzed according to the treatment they received. One patient was not included in the SAF due to mis-randomization.

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

Outcome measures

Measure	LCZ696 200 mg n=188 Participants Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 Participants Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Number of Patients With Total Adverse Events, Serious Adverse Events and Death Deaths	0 Number of participants	0 Number of participants
Number of Patients With Total Adverse Events, Serious Adverse Events and Death Adverse events (serious and non-serious)	44 Number of participants	41 Number of participants
Number of Patients With Total Adverse Events, Serious Adverse Events and Death Serious Adverse Events	0 Number of participants	2 Number of participants

Adverse Events

LCZ696 200 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Olmesartan 20 mg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	LCZ696 200 mg n=188 participants at risk Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 participants at risk Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BENIGN NEOPLASM OF THYROID GLAND	0.00% 0/188	0.53% 1/187
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.00% 0/188	0.53% 1/187

Other adverse events

Measure	LCZ696 200 mg n=188 participants at risk Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Olmesartan 20 mg n=187 participants at risk Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
Nervous system disorders DIZZINESS	1.1% 2/188	2.1% 4/187
Nervous system disorders HEADACHE	2.7% 5/188	3.2% 6/187

Additional Information

Study Director

Novartis Pharmaceuticals

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