Efficacy and Safety of LCZ696A in Patients With Essential Hypertension

NCT00549770 | Completed Phase 2 Results

• 1 other identifier: CLCZ696A2201
• Study Type: interventional
• Target: 1,334
• Locations: 18 countries
• Sites: 182

Brief Summary

This study was a dose-ranging efficiacy study in patients with essential hypertension to assess the blood pressure lowering effect, and safety of LCZ696 compared to valsartan and placebo. The study will also evaluate the efficacy and safety of AHU377 as compared to placebo.

Conditions

Hypertension

Keywords

Hypertension, valsartan, LCZ696

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)

  Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.

  baseline, week 8

Secondary Outcomes (8)

• Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)

  baseline, week 8

• Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP

  baseline, 8 weeks

• Change From Baseline in Daytime maDBP and maSBP

  baseline, 8 weeks

• Change From Baseline in Nighttime maDBP and maSBP

  baseline, 8 weeks

• Percentage of Participants Who Achieved a Successful Response in msDBP

  8 weeks

Study Arms (8)

LCZ696 100 mg

EXPERIMENTAL

Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Drug: LCZ696; Drug: Placebo

LCZ696 200 mg

EXPERIMENTAL

Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Drug: LCZ696; Drug: Placebo

LCZ696 400 mg

EXPERIMENTAL

Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Drug: LCZ696; Drug: Placebo

Valsartan 80 mg

ACTIVE COMPARATOR

Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Drug: Valsartan; Drug: Placebo

Valsartan 160 mg

ACTIVE COMPARATOR

Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily.

Drug: Valsartan; Drug: Placebo

Valsartan 320 mg

ACTIVE COMPARATOR

Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Drug: Valsartan; Drug: Placebo

AHU377 200 mg

EXPERIMENTAL

Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.

Drug: AHU377; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Drug: Placebo

Interventions

LCZ696 DRUG

LCZ696 100 mg; LCZ696 200 mg; LCZ696 400 mg

Valsartan DRUG

Valsartan 160 mg; Valsartan 320 mg; Valsartan 80 mg

AHU377 DRUG

AHU377 200 mg

Placebo DRUG

AHU377 200 mg; LCZ696 100 mg; LCZ696 200 mg; LCZ696 400 mg; Placebo; Valsartan 160 mg; Valsartan 320 mg; Valsartan 80 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or females from 18 up to and including 75 years
• Patients with mild-to-moderate uncomplicated essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy of 2 drugs; therapy with a fixed dose combination of two active substances represents 2 drugs)
• Untreated patients must have had an office msDBP≥ 95 mmHg at the randomization visit (Visit 3) and the 2 preceding visits (Visits 1 and 2).
• Treated patients must have had an office msDBP≥ 90 mmHG after washout (Visit 2), and a msDBP\> 95 mmHg at baseline (Visit 3);

You may not qualify if:

• Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg)
• History of angioedema, drug-related or otherwise, as reported by the patient
• Type 1 or Type 2 diabetes mellitus (according to the ADA criteria)
• History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, drug-induced hypertension, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease, etc.
• History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (182)

Novartis Investigative Site

Birmingham, Alabama, 35294-2041, United States

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Muscle Shoals, Alabama, 35662, United States

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Chandler, Arizona, 85224, United States

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Buena Park, California, 90620, United States

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Fair Oaks, California, 95628, United States

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Long Beach, California, 90806, United States

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Los Angeles, California, 90057, United States

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Orangevale, California, 95662, United States

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Santa Ana, California, 92701, United States

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Stockton, California, 95204, United States

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Tustin, California, 92780, United States

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Jacksonville, Florida, 32216, United States

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Pembroke Pines, Florida, 33024, United States

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Pembroke Pines, Florida, 33029, United States

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Pensacola, Florida, 32504, United States

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Augusta, Georgia, 30904, United States

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Chicago, Illinois, 60607, United States

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Chicago, Illinois, 60610, United States

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Peoria, Illinois, 61615, United States

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Baton Rouge, Louisiana, 70809, United States

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Metairie, Louisiana, 70006, United States

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Chelsea, Michigan, 48118, United States

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Royal Oak, Michigan, 48073, United States

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Brooklyn Center, Minnesota, 55430-2168, United States

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City of Saint Peters, Missouri, 63376, United States

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Toms River, New Jersey, 08753, United States

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Trenton, New Jersey, 08629, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45224, United States

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Oklahoma City, Oklahoma, 73132-4904, United States

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Simpsonville, South Carolina, 29681, United States

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Dallas, Texas, 75235, United States

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Houston, Texas, 77030-3411, United States

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Houston, Texas, 77081, United States

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Houston, Texas, 77083, United States

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Lake Jackson, Texas, 77566, United States

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Richmond, Virginia, 23294, United States

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Charleston, West Virginia, 25301, United States

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Caba, Buenos Aires, C1408INH, Argentina

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Caba, Buenos Aires, C1416DRJ, Argentina

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Caba, Buenos Aires, C1425AST, Argentina

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Corrientes, Corrientes Province, W3400, Argentina

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Rosario, Santa Fe Province, S2000CXH, Argentina

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Cambridge, Ontario, N1R 6V6, Canada

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Mississauga, Ontario, M4T 4J2, Canada

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Toronto, Ontario, M9W 4L6, Canada

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Granby, Quebec, J2G 8Z9, Canada

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Longueil, Quebec, J4N 1L6, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Sherbrooke, Quebec, J1J 2G2, Canada

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Ste-Foy, Quebec, G1V 4G2, Canada

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Saskatoon, Saskatchewan, S7H 5M3, Canada

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Aalborg, DK-9000, Denmark

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Aalborg SV, 9200, Denmark

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Espergærde, 3060, Denmark

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Greve, 2670, Denmark

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Roslev, 7870, Denmark

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Vaerloese, DK-3500, Denmark

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Viborg, 8800, Denmark

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Helsinki, 00180, Finland

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Helsinki, 00350, Finland

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Helsinki, 00810, Finland

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Kerava, 04200, Finland

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Oulu, 90100, Finland

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Tampere, 33100, Finland

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Bourges, 18000, France

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La Chapelle-sur-Erdre, 44240, France

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La Roche-sur-Yon, 85000, France

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Le Pradet, 83220, France

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Murs Erigné, 49610, France

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Saint-Avertin, 37550, France

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Tours, 37000, France

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Vihiers, 49310, France

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Balve, 58802, Germany

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Beckingen, 66701, Germany

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Berlin, 10719, Germany

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Berlin, 13053, Germany

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Einbeck, 37574, Germany

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Erfurt, 99084, Germany

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Giengen an der Brenz, 89537, Germany

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Hagen, 58095, Germany

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Haigerloch, 72401, Germany

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Hamburg, 22335, Germany

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Kassel, 34125, Germany

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Krefeld, 47798, Germany

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Mahlberg, 77972, Germany

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Messkirch, 88605, Germany

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Reinfeld, 23858, Germany

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Siegen, 57074, Germany

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Wallerfing, 94574, Germany

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Warendorf, 48231, Germany

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Budapest, 1134, Hungary

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Esztergom, 2500, Hungary

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Miskolc, 3526, Hungary

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Nyiregyháza, 4400, Hungary

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Caserta, CE, 81100, Italy

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Cona, FE, 44100, Italy

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Florence, FI, 50134, Italy

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Pozzilli, IS, 86077, Italy

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Rozzano, MI, 20089, Italy

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Vimercate, MI, 20059, Italy

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Palermo, PA, 90127, Italy

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Padua, PD, 35128, Italy

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Pisa, PI, 56124, Italy

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Pisa, PI, 56126, Italy

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Casorate Primo, PV, 27022, Italy

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Pavia, PV, 27100, Italy

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Stradella, PV, 27049, Italy

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Mercato San Severino, SA, 84085, Italy

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Sassari, SS, 07100, Italy

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San Daniele del Friuli, UD, 33038, Italy

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Vibo Valentia, VV, 89900, Italy

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Daugavplis, LV-5417, Latvia

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Kuldīga, LV-3300, Latvia

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Ogre, 5001, Latvia

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Riga, 1002, Latvia

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Riga, LV-1001, Latvia

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Riga, LV-1012, Latvia

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Alytus, LT-62381, Lithuania

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Kaunas, 3007, Lithuania

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Kaunas, LT-47144, Lithuania

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Kaunas, LT-49387, Lithuania

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Klaipėda, LT-92288, Lithuania

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's-Hertogenbosch, 5216 GC, Netherlands

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Deurne, 5751 XJ, Netherlands

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Ermelo, 3851 EX, Netherlands

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Hoogwoud, 1718 BG, Netherlands

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Leeuwarden, 8934 AD, Netherlands

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Losser, 7581 BV, Netherlands

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Oude Pekela, 9665 AR, Netherlands

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Poortvliet, 4693 BT, Netherlands

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Wamel, 6659 BX, Netherlands

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Ostrów Wielkopolski, 63-400, Poland

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Oława, 55-200, Poland

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Tarnów, 33-100, Poland

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Moscow, 101990, Russia

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Moscow, 105077, Russia

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Moscow, 121552, Russia

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S.-Petersburg, 191187, Russia

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S.-Petersburg, 196247, Russia

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Saint Petersburg, 194044, Russia

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Saint Petersburg, 195067, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197341, Russia

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Banská Bystrica, Slovak Republic, 974 05, Slovakia

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Bratislava, Slovak Republic, 813 69, Slovakia

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Nitra, Slovak Republic, 949 01, Slovakia

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Prešov, Slovak Republic, 080 01, Slovakia

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Dunajská Streda, 929 01, Slovakia

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Žilina, 012 07, Slovakia

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Seville, Andalusia, 41009, Spain

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Palma de Mallorca, Balearic Islands, 07007, Spain

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Badalona, Catalonia, 08914, Spain

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Barcelona, Catalonia, 08025, Spain

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Barcelona, Catalonia, 08905, Spain

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Tàrrega, Catalonia, 25300, Spain

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Vic, Catalonia, 08500, Spain

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Begonte, Galicia, 27373, Spain

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Santiago de Compostela, Galicia, 15706, Spain

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Madrid, Madrid, 28046, Spain

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Alicante, Valencia, 03004, Spain

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Benidorm, Valencia, 03550, Spain

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Quart de Poblet, Valencia, 46930, Spain

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Valencia, Valencia, 460009, Spain

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Barcelona, 08820, Spain

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Hospitalet de Llbregat, 08902, Spain

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Petrel, 03610, Spain

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Riudecols, 43390, Spain

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Boden, Sweden, SE 961 31, Sweden

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Skellefteå, Sweden, SE 931 32, Sweden

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Arvidsjaur, 933 83, Sweden

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Karlstad, 652 25, Sweden

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Kil, 665 30, Sweden

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Kristianstad, 291 54, Sweden

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Lund, SE-222 21, Sweden

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Taipei, Taiwan, 10449, Taiwan

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Taipei, Taiwan, 114, Taiwan

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Taichung, Taiwan ROC, 40201, Taiwan

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Tainan, Taiwan ROC, Taiwan

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Changhua, 500, Taiwan

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Taichung County, Taiwan

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Taipei, 112, Taiwan

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Related Publications (2)

• Andersen MB, Simonsen U, Wehland M, Pietsch J, Grimm D. LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):14-22. doi: 10.1111/bcpt.12453. Epub 2015 Sep 4.

  PMID: 26280447 DERIVED

• Ruilope LM, Dukat A, Bohm M, Lacourciere Y, Gong J, Lefkowitz MP. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet. 2010 Apr 10;375(9722):1255-66. doi: 10.1016/S0140-6736(09)61966-8. Epub 2010 Mar 16.

  PMID: 20236700 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan; sacubitril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2007
• First Posted: October 26, 2007
• Study Start: September 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: August 25, 2015
• Results First Posted: August 10, 2015

Record last verified: 2015-08

Locations

HU (4); ES (18); FR (8); RU (9); PL (3); TW (7); AR (5); IT (17); DE (18); LA (6); CA (9); LI (5); NL (9); DK (7); SL (6); US (38); FI (6); SE (7)