An 8-week Study to Evaluate the Dose Response of AHU377 in Combination With Valsartan 320 mg in Patients With Mild-to-moderate Systolic Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01281306
First received: January 20, 2011
Last updated: January 27, 2013
Last verified: January 2013
  Purpose

The purpose of the study is to evaluate dose response of blood pressure lowering for 4 doses of AHU377, given once daily (50 mg, 100 mg, 200 mg and 400 mg) in combination with a fixed dose of valsartan (320 mg).


Condition Intervention Phase
Systolic Hypertension
Drug: LCZ696
Drug: AHU377
Drug: Valsartan
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group Study to Evaluate the Dose Response of AHU377 in Combination With Valsartan 320 mg After 8 Week Treatment in Patients With Mild-to-moderate Systolic Hypertension

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • reduction in mean sitting systolic blood pressure (msSBP) [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • dose-response relationship in sitting diastolic blood pressure (msDBP) lowering of ascending doses of AHU377 in combination with valsartan 320 mg [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
  • changes in mean 24 hour ambulatory SBP (maSBP), mean 24 hour ambulatory DBP (maDBP), daytime and nighttime msSBP/maDBP of ascending doses of AHU377 in combination with valsartan 320mg as compared to valsartan 320mg monotherapy [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
  • office and ambulatory pulse pressure for all treatment groups [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
  • dose-response relationship in msSBP/msDBP and maSBP/maDBP lowering of ascending doses of AHU377 in combination with valsartan 320mg by sub-group analysis of age (< 65 and ≥ 65) [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
  • Frequency of adverse events, serious adverse events, and notable laboratory abnormalities [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 1301
Study Start Date: January 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 400 mg
patients will start with 200mg LCZ696 qd for one week, thereafter they will be up-titrated to 400 mg LCZ696 given once daily for the remaining 7 weeks
Drug: LCZ696
LCZ696 400 mg, LCZ696 200 mg
Experimental: AHU377 400 mg + valsartan 320 mg
patients will start with AHU377 100mg + valsartan 160 mg for one week, they will be up-titrated to AHU377 200 mg + valsartan 320 mg for one week and thereafter they will be up-titrated to AHU377 400 mg +valsartan 320 mg for the remaining 6 weeks
Drug: AHU377
AHU377 100 mg, AHU377 50 mg
Drug: Valsartan
Valsartan 320 mg, Valsartan 160 mg
Experimental: AHU377 200 mg + valsartan 320 mg
patients will start with AHU377 100 mg + valsartan 160 mg for one week, thereafter they will be up-titrated to AHU377 200 mg + valsartan 320 mg for the remaining 7 weeks
Drug: AHU377
AHU377 100 mg, AHU377 50 mg
Drug: Valsartan
Valsartan 320 mg, Valsartan 160 mg
Experimental: AHU377 100 mg + valsartan 320 mg
patient will start with AHU377 50 mg + valsartan 160 mg for one week, thereafter they will be up-titrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks
Drug: AHU377
AHU377 100 mg, AHU377 50 mg
Drug: Valsartan
Valsartan 320 mg, Valsartan 160 mg
Experimental: AHU377 50 mg + valsartan 320 mg
patients will start with AHU377 50 mg + valsartan 160 mg for one week, thereafter they will be up-titrated to AHU377 50 mg + valsartan 320 mg for the remaining 7 weeks
Drug: AHU377
AHU377 100 mg, AHU377 50 mg
Drug: Valsartan
Valsartan 320 mg, Valsartan 160 mg
Experimental: valsartan 320 mg
patients will start with valsartan 160 mg for one week, thereafter they will be up-titrated to valsartan 320 mg for the remaining 7 weeks
Drug: Valsartan
Valsartan 320 mg, Valsartan 160 mg
Experimental: placebo
patients will receive matching placebo for 8 weeks
Drug: placebo

  Eligibility

Ages Eligible for Study:   18 Years to 76 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed. Patients with mild-to-moderate systolic hypertension, untreated or currently taking antihypertensive therapy.
  • Ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥ 80% compliance rate) during the run-in period.

Exclusion Criteria:

  • Severe hypertension
  • History of angioedema, drug-related or otherwise, as reported by the patient.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential (WOCBP), UNLESS they are using adequate birth control methods.
  • History or evidence of a secondary form of hypertension.
  • Other protocol-defined inclusion/exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281306

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Locations
United States, Florida
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Clearwater, Florida, United States, 33756
United States, Illinois
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Chicago, Illinois, United States, 60607
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Chicago, Illinois, United States, 60610
United States, Louisiana
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Metairie, Louisiana, United States, 70006
United States, Mississippi
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Belzoni, Mississippi, United States, 39038
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Jackson, Mississippi, United States, 39202
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Jackson, Mississippi, United States, 39209
United States, Missouri
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St. Louis, Missouri, United States, 63031
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St. Louis, Missouri, United States, 63141
United States, Nevada
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Henderson, Nevada, United States, 89014
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Las Vegas, Nevada, United States, 89119
United States, New York
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Buffalo, New York, United States, 14215
United States, North Carolina
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Charlotte, North Carolina, United States, 28277
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Greensboro, North Carolina, United States, 27408
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Greensboro, North Carolina, United States, 27401
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Shelby, North Carolina, United States, 28152
United States, Pennsylvania
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Erie, Pennsylvania, United States, 16509
United States, Texas
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Bryan, Texas, United States, 77802
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Houston, Texas, United States, 77030
Argentina
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Rosario, Santa Fe, Argentina, S2000AII
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Rosario, Santa Fe, Argentina, S2132XAC
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San Miguel de Tucuman, Tucuman, Argentina, T4000EBR
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Buenos Aires, Argentina, C1440AAD
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Buenos aires, Argentina, C1120AAC
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Buenos Aires, Argentina, B8000XAV
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Capital Federal, Argentina, C1179AAB
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Cordoba, Argentina, X5003DCP
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Corrientes, Argentina, 3400
Canada, Newfoundland and Labrador
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Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
Canada, Quebec
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Mirabel, Quebec, Canada, J7J 2K8
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Ste-Foy, Quebec, Canada, G1V 4G2
Hungary
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Budapest, Hungary, 1136
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Budapest, Hungary, 1045
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Csongrad, Hungary, 6640
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Erd, Hungary, H-2030
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Miskolc, Hungary, 3530
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Miskolc, Hungary, 3525
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Nyiregyháza, Hungary, 4400
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Szeged, Hungary, H-6720
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Torokbalint, Hungary, 2045
India
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Vishakhapatnam, Andhra Pradesh, India, 530002
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Ahmedabad, Gujarat, India, 380 051
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Nashik, Maharashtra, India, 422005
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Nashik, Maharashtra, India, 422 005
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Pune, Maharashtra, India, 411005
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Ludhiana, Punjab, India, 141002
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Jaipur, Rajasthan, India, 302016
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Lucknow, Uttar Pradesh, India, 226005
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Lucknow, Uttar Pradesh, India, 226003
Korea, Republic of
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Bucheon, Gyeonggi-do, Korea, Republic of, 424-717
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Goyang, Gyeonggi-do, Korea, Republic of, 411-706
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Uijeongbu-Si, Gyeonggi-do, Korea, Republic of, 480-717
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Koyang, Kyunggi, Korea, Republic of, 410-719
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Seoul, Korea, Republic of, 738-736
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Seoul, Korea, Republic of, 137-701
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Seoul, Korea, Republic of, 152-703
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Seoul, Korea, Republic of, 150-950
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Seoul, Korea, Republic of, 150-713
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Seoul, Korea, Republic of, 140-743
Romania
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Bucharest, District 1, Romania
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Bucharest, District 1, Romania, 012064
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Bucharest, District 1, Romania, 011422
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Bucharest, District 2, Romania, 021705
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Bucuresti, District 2, Romania, 021345
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Oradea, Jud. Bihor, Romania, 410032
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Craiova, Jud. Dolj, Romania, 200147
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Bucharest, Romania, 060011
Slovakia
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Nitra, Slovak Republic, Slovakia, 949 01
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Presov, Slovak Republic, Slovakia, 08001
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Bratislava, Slovakia, 831 06
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Liptovsky Mikulas, Slovakia, 031 01
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Nitra, Slovakia, 949 01
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Nitra, Slovakia, 94901
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Nove Zamky, Slovakia, 940 01
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Partizanske, Slovakia, 958 01
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Presov, Slovakia, 081 01
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Presov, Slovakia, 080 01
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Ruzomberok, Slovakia, 034 26
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Sala, Slovakia, 927 03
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Sered, Slovakia, 926 00
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Zvolen, Slovakia, 960 01
Spain
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Granada, Andalucía, Spain, 18012
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Sevilla, Andalucía, Spain, 41009
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Badalona, Barcelona, Spain, 08914
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Centelles, Barcelona, Spain, 08540
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Alzira, Comunidad Valenciana, Spain, 46600
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Santiago de Compostela, Galicia, Spain, 15706
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Alicante, Spain, 03114
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Barcelona, Spain
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Madrid, Spain, 28046
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Tarragona, Spain, 43350
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01281306     History of Changes
Other Study ID Numbers: CLCZ696A2223, 2010-022326-32
Study First Received: January 20, 2011
Last Updated: January 27, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Human Research Bioethics Committee
Canada: Therapeutic Products Directorate at Health Canada
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency of Medicine (Agentia Nationala a Medicamentului)
South Korea: Korea Food and Drug Administration (KFDA)
Slovakia: State Institute for Drug Control
Spain: Agencia Espanola del Medicamento y Productos Sanitarios (AEMPS)

Keywords provided by Novartis:
hypertension
blood pressure
LCZ696
dual-acting
neprilysin
nep inhibitor
vasopeptidase
angiotensin receptor
angiotensin receptor neprilysin inhibitor (ARNi)

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Valsartan
3-(1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-3'-methyl-2'-(pentanoyl(2'-(tetrazol-5-ylate)biphenyl-4'-ylmethyl)amino)butyrate
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014