Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Japanese Patients With Essential Hypertension

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01599104
• Collaborator: (none)
• Enrollment: 1,161
• Locations: 61
• Arms: 3
• Duration (Months): 10
• Patients Per Site: 19
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

This study assessed the efficacy of LCZ696 in Japanese patients with essential hypertension

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: LCZ696; Drug: Olmesartan; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Active-controlled, 8-week Study to Evaluate the Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Japanese Patients With Essential Hypertension
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LCZ696 200 mg LCZ696 200 mg tablet and placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) tablet once daily for 8 weeks	Drug: LCZ696; 200 mg (one tablet) or 400 mg (2 tablets of 200mg) once daily; Drug: Placebo; Placebo to LCZ696 or Olmesartan
Experimental: LCZ696 400 mg LCZ696 200 mg tablet and a placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) once daily for one week; then up-titrated to LCZ696 400 mg and placebo to Olmesartan (1 capsule) once daily for the remaining 7 weeks	Drug: LCZ696; 200 mg (one tablet) or 400 mg (2 tablets of 200mg) once daily; Drug: Placebo; Placebo to LCZ696 or Olmesartan
Active Comparator: Olmesartan 20 mg Olmesartan 20 mg capsule and placebo to LCZ696 (2 tablets) once daily for 8 weeks	Drug: Olmesartan; Olmesartan 20 mg capsule one daily; Drug: Placebo; Placebo to LCZ696 or Olmesartan

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [Baseline, 8 weeks]

   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. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.

Secondary Outcome Measures

1. Change From Baseline in Mean 24-hour Ambulatory SBP (maSBP) at Week 8 [Baseline, 8 weeks]

   Ambulatory blood pressure monitoring (ABPM) over a 24-hour period was conducted at two time-points during the study in a subset of participants.

2. Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) [Baseline, 8 weeks]

   Sitting BP measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.

3. Percentage of Participants Achieving a Successful Response in Overall Blood Pressure Control at Week 8 [8 weeks]

   A successful response in overall BP control rate was defined as msSBP < 140 mmHg and msDBP <90 mmHg.

4. Percentage of Participants Achieving a Successful msSBP Response [8 weeks]

   Successful msSBP response was defined as < 140 mmHg or ≥ 20 mmHg reduction from baseline.

5. Percentage of Participants Achieving a Successful msDBP Response [8 weeks]

   Successfull msDBP response was defined as <90 mmHg or ≥10 mmHg reduction from baseline.

6. Change From Baseline in Mean 24-hour Ambulatory DBP (maDBP) at Week 8 [Baseline, 8 weeks]

   ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.

7. Change From Baseline in maSBP and maDBP for Daytime/Nighttime [Baseline, 8 weeks]

   ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.

8. Change From Baseline in Office Pulse Pressure [Baseline, 8 weeks]

   Office pulse pressure was calculated as msSBP minus msDBP. Sitting blood pressure (BP) measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and then averaged to calculate the mean BP value. The baseline PP value was subtracted from the week 8 PP value to determine the change from baseline in PP.

9. Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure [Baseline, 8 weeks]

   Ambulatory pulse pressure was calculated as hourly ambulatory SBP minus hourly ambulatory DBP in a subset of participants.

10. Number of Patients With Adverse Events, Serious Adverse Events and Death [8 weeks]

    Participants were monitored for adverse events, serious adverse events and deaths throughout the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with mild-to-moderate hypertension, untreated or currently taking antihypertensive therapy.

• Treated patients (using antihypertensive treatments within 4 weeks prior to Visit 1) must have an msSBP ≥ 150 mmHg and < 180 mmHg at the randomization visit (Visit 201) and msSBP ≥140 mmHg < 180 mmHg at the visit immediately proceeding Visit 201 (Visit 102 or 103).

• Untreated patients (newly diagnosed with essential hypertension or having a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to Visit 1) must have an msSBP ≥ 150 mmHg and < 180 mmHg at both Visit 1 and Visit 201.

• Patients must have an absolute difference of ≤15 mmHg in msSBP between Visit 201 and the immediately preceding visit;

Exclusion Criteria:

• Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).

• History of angioedema, drug-related or otherwise, as reported by the patient.

• History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension.

• Patients who previously entered a LCZ696 study and had been randomized or enrolled into the active drug treatment epoch.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Kamogawa-City	Chiba	Japan	296-8602
2	Novartis Investigative Site	Chikushi-gun	Fukuoka	Japan	811-1244
3	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	810-0014
4	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	810-0066
5	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	812-8582
6	Novartis Investigative Site	Kitakyushu-city	Fukuoka	Japan	800-0225
7	Novartis Investigative Site	Kitakyushu-city	Fukuoka	Japan	807-0856
8	Novartis Investigative Site	Asahikawa	Hokkaido	Japan	078-8214
9	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	006-0811
10	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	062-0053
11	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	063-0842
12	Novartis Investigative Site	Sapporo	Hokkaido	Japan	003-0026
13	Novartis Investigative Site	Sapporo	Hokkaido	Japan	003-0825
14	Novartis Investigative Site	Amagasaki	Hyogo	Japan	660-0814
15	Novartis Investigative Site	Hitachi-city	Ibaraki	Japan	317-0077
16	Novartis Investigative Site	Kawasaki-city	Kanagawa	Japan	210-0852
17	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	231-0023
18	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	236-0004
19	Novartis Investigative Site	Kyotanabe-city	Kyoto	Japan	610-0361
20	Novartis Investigative Site	Kyoto-city	Kyoto	Japan	615-0035
21	Novartis Investigative Site	Kyoto-city	Kyoto	Japan	615-8125
22	Novartis Investigative Site	Kashihara-city	Nara	Japan	634-8522
23	Novartis Investigative Site	Ibadraki	Osaka	Japan	567-0876
24	Novartis Investigative Site	Osaka-city	Osaka	Japan	547-0013
25	Novartis Investigative Site	Toyonaka-city	Osaka	Japan	560-0082
26	Novartis Investigative Site	Ageo-city	Saitama	Japan	362-8588
27	Novartis Investigative Site	Fujimino	Saitama	Japan	356-0053
28	Novartis Investigative Site	Hiki-Gun	Saitama	Japan	355-0328
29	Novartis Investigative Site	Koshigaya city	Saitama	Japan	343-0826
30	Novartis Investigative Site	Niiza-city	Saitama	Japan	352-0014
31	Novartis Investigative Site	Sakado	Saitama	Japan	350-0202
32	Novartis Investigative Site	Tokorozawa-city	Saitama	Japan	359-1161
33	Novartis Investigative Site	Shimotsuke-city	Tochigi	Japan	329-0498
34	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-0031
35	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-8655
36	Novartis Investigative Site	Chiyoda-ku	Tokyo	Japan	100-0005
37	Novartis Investigative Site	Edogawa-ku	Tokyo	Japan	133-0061
38	Novartis Investigative Site	Edogawa-ku	Tokyo	Japan	134-0084
39	Novartis Investigative Site	Hachioji-city	Tokyo	Japan	192-0918
40	Novartis Investigative Site	Hachioji	Tokyo	Japan	192-0046
41	Novartis Investigative Site	Katsushika-ku	Tokyo	Japan	124-0024
42	Novartis Investigative Site	Kiyose-city	Tokyo	Japan	204-0021
43	Novartis Investigative Site	Kunitachi	Tokyo	Japan	186-0001
44	Novartis Investigative Site	Meguro-ku	Tokyo	Japan	152-0031
45	Novartis Investigative Site	Minato-ku	Tokyo	Japan	105-7390
46	Novartis Investigative Site	Minato-ku	Tokyo	Japan	108-0075
47	Novartis Investigative Site	Nerima-ku	Tokyo	Japan	177-0051
48	Novartis Investigative Site	Ota-ku	Tokyo	Japan	143-0023
49	Novartis Investigative Site	Shibuya-ku	Tokyo	Japan	150-0002
50	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	141-0032
51	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	142-0053
52	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	142-0063
53	Novartis Investigative Site	Shinjuku-ku	Tokyo	Japan	160-8582
54	Novartis Investigative Site	Tachikawa	Tokyo	Japan	190-0013
55	Novartis Investigative Site	Taito	Tokyo	Japan	111-0052
56	Novartis Investigative Site	Toshima-ku	Tokyo	Japan	171-0021
57	Novartis Investigative Site	Fukuoka		Japan	814-0032
58	Novartis Investigative Site	Osaka		Japan	536-0008
59	Novartis Investigative Site	Osaka		Japan	550-0013
60	Novartis Investigative Site	Osaka		Japan	560-0005
61	Novartis Investigative Site	Saitama		Japan	337-0012

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01599104
• Other Study ID Numbers: CLCZ696A1306
• First Posted: May 15, 2012
• Last Update Posted: Oct 16, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Essential hypertension; LCZ696
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Olmesartan; Sacubitril and valsartan sodium hydrate drug combination

Study Results

Participant Flow

Recruitment Details	The study consisted of 3 epochs: 1)screening, 2) single blind run-in and 3) double blind treatment. During the run-in epoch, eligible participants received placebo to both treatments for 2 to 4 weeks. After the run-in epoch, a total of 1161 eligible participants continued into the double blind treatment epoch for 8 weeks.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Period Title: Overall Study
STARTED	387	385	389
COMPLETED	371	371	363
NOT COMPLETED	16	14	26

Baseline Characteristics

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg	Total
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks	Total of all reporting groups
Overall Participants	387	385	389	1161
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.9 (10.87)	58.7 (10.50)	59.6 (10.50)	58.7 (10.64)
Sex: Female, Male (Count of Participants)
Female	123 31.8%	117 30.4%	103 26.5%	343 29.5%
Male	264 68.2%	268 69.6%	286 73.5%	818 70.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Description	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. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The full analysis set included all randomized participants who received study medication and had both baseline and post-baseline BP assessments.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	387	385	389
Least Squares Mean (Standard Error) [mmHg]	-18.21 (0.702)	-20.18 (0.704)	-13.20 (0.700)

2. Secondary Outcome

Title	Change From Baseline in Mean 24-hour Ambulatory SBP (maSBP) at Week 8
Description	Ambulatory blood pressure monitoring (ABPM) over a 24-hour period was conducted at two time-points during the study in a subset of participants.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline ABPM measurements. This outcome measure was analyzed in a subset of participants within each treatment group where n = 216 for the LCZ 200 mg group, n = 216 for the LCZ 400 mg group and n = 200 for the Olmesartan group.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	216	216	200
Least Squares Mean (Standard Error) [mmHg]	-13.44 (0.445)	-14.99 (0.445)	-8.78 (0.462)

3. Secondary Outcome

Title	Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Description	Sitting BP measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline BP measurements.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	387	385	389
Least Squares Mean (Standard Error) [mmHg]	-7.76 (0.404)	-8.79 (0.406)	-5.91 (0.404)

4. Secondary Outcome

Title	Percentage of Participants Achieving a Successful Response in Overall Blood Pressure Control at Week 8
Description	A successful response in overall BP control rate was defined as msSBP < 140 mmHg and msDBP <90 mmHg.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline BP measurements.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	387	385	389
Number [Percentage of participants]	43.9 11.3%	46.5 12.1%	32.9 8.5%

5. Secondary Outcome

Title	Percentage of Participants Achieving a Successful msSBP Response
Description	Successful msSBP response was defined as < 140 mmHg or ≥ 20 mmHg reduction from baseline.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline BP measurements.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	387	385	389
Number [Percentage of participants]	57.9 15%	63.1 16.4%	42.9 11%

6. Secondary Outcome

Title	Percentage of Participants Achieving a Successful msDBP Response
Description	Successfull msDBP response was defined as <90 mmHg or ≥10 mmHg reduction from baseline.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline BP measurements.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	387	385	389
Number [Percentage of participants]	69.5 18%	70.1 18.2%	60.7 15.6%

7. Secondary Outcome

Title	Change From Baseline in Mean 24-hour Ambulatory DBP (maDBP) at Week 8
Description	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline ABPM measurements. This outcome measure was analyzed in a subset of participants within each treatment group where n = 216 for the LCZ 200 mg group, n = 216 for the LCZ 400 mg group and n = 200 for the Olmesartan group.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	216	216	200
Least Squares Mean (Standard Error) [mmHg]	-7.65 (0.295)	-8.44 (0.295)	-5.56 (0.307)

8. Secondary Outcome

Title	Change From Baseline in maSBP and maDBP for Daytime/Nighttime
Description	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline ABPM measurements. This outcome measure was analyzed in a subset of participants within each treatment group where n = 216 for the LCZ 200 mg group, n = 216 for the LCZ 400 mg group and n = 200 for the Olmesartan group.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	216	216	200
maSBP daytime	-12.60 (0.747)	-14.44 (0.747)	-7.87 (0.776)
maSBP nighttime	-15.13 (0.747)	-16.09 (0.747)	-10.65 (0.776)
maDBP daytime	-7.01 (0.506)	-8.00 (0.506)	-4.95 (0.526)
maDBP nighttime	-8.82 (0.506)	-9.42 (0.506)	-6.79 (0.526)

9. Secondary Outcome

Title	Change From Baseline in Office Pulse Pressure
Description	Office pulse pressure was calculated as msSBP minus msDBP. Sitting blood pressure (BP) measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and then averaged to calculate the mean BP value. The baseline PP value was subtracted from the week 8 PP value to determine the change from baseline in PP.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline BP measurements.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	387	385	389
Least Squares Mean (Standard Error) [mmHg]	-10.49 (0.471)	-11.30 (0.472)	-7.34 (0.470)

10. Secondary Outcome

Title	Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure
Description	Ambulatory pulse pressure was calculated as hourly ambulatory SBP minus hourly ambulatory DBP in a subset of participants.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received study medication, and had both baseline and post-baseline ABPM measurements. This outcome measure was analyzed in a subset of participants within each treatment group where n = 216 for the LCZ 200 mg group, n = 216 for the LCZ 400 mg group and n = 200 for the Olmesartan group.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	216	216	200
Least Squares Mean (Standard Error) [mmHg]	-5.79 (0.208)	-6.57 (0.207)	-3.20 (0.216)

11. Secondary Outcome

Title	Number of Patients With Adverse Events, Serious Adverse Events and Death
Description	Participants were monitored for adverse events, serious adverse events and deaths throughout the study.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Set. The safety set included aqll participants who had received study medication.

Arm/Group Title	LCZ696 200 mg	LCZ696 400 mg	Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks	LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks	Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
Measure Participants	387	385	389
Adverse Events (serious and non-serious)	135 34.9%	136 35.3%	152 39.1%
Seroius Adverse Events	1 0.3%	1 0.3%	7 1.8%
Deaths	0 0%	0 0%	0 0%

Adverse Events

Arm/Group Title	LCZ696 200 mg		LCZ696 400 mg		Olmesartan 20 mg
Arm/Group Description	LCZ696 200 mg tablet and a placebo tablet once daily for eight weeks		LCZ696 200 mg tablet and a placebo tablet once daily for one week, then up-titrated to 400 mg once daily for the remaining 7 weeks		Olmesartan 20 mg tablet and a placebo tablet once daily for 8 weeks
All Cause Mortality
	LCZ696 200 mg		LCZ696 400 mg		Olmesartan 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LCZ696 200 mg		LCZ696 400 mg		Olmesartan 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/387 (0.3%)		1/385 (0.3%)		7/389 (1.8%)
Cardiac disorders
ARTERIOSCLEROSIS CORONARY ARTERY	0/387 (0%)		1/385 (0.3%)		0/389 (0%)
SUPRAVENTRICULAR TACHYCARDIA	0/387 (0%)		0/385 (0%)		1/389 (0.3%)
Eye disorders
CATARACT	0/387 (0%)		0/385 (0%)		1/389 (0.3%)
Hepatobiliary disorders
BILE DUCT STONE	0/387 (0%)		0/385 (0%)		1/389 (0.3%)
HEPATOBILIARY DISEASE	0/387 (0%)		1/385 (0.3%)		0/389 (0%)
Injury, poisoning and procedural complications
RADIUS FRACTURE	0/387 (0%)		0/385 (0%)		1/389 (0.3%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	0/387 (0%)		0/385 (0%)		1/389 (0.3%)
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS	0/387 (0%)		0/385 (0%)		1/389 (0.3%)
Nervous system disorders
CEREBRAL INFARCTION	0/387 (0%)		0/385 (0%)		1/389 (0.3%)
SUBARACHNOID HAEMORRHAGE	1/387 (0.3%)		0/385 (0%)		0/389 (0%)
Other (Not Including Serious) Adverse Events
	LCZ696 200 mg		LCZ696 400 mg		Olmesartan 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/387 (12.4%)		47/385 (12.2%)		46/389 (11.8%)
Infections and infestations
NASOPHARYNGITIS	48/387 (12.4%)		47/385 (12.2%)		46/389 (11.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.