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

NCT01281306 | Completed Phase 2 Results

• 2 other identifiers: CLCZ696A22232010-022326-32
• Study Type: interventional
• Target: 910
• Locations: 9 countries
• Sites: 90

Brief Summary

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).

Conditions

Systolic Hypertension

Keywords

hypertension; blood pressure; LCZ696; dual-acting; neprilysin; nep inhibitor; vasopeptidase; angiotensin receptor; angiotensin receptor neprilysin inhibitor (ARNi)

Outcome Measures

Primary Outcomes (1)

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

  Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.

  Baseline, 8 weeks

Secondary Outcomes (14)

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

  Baseline, 8 weeks

• Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP)

  Baseline, 8 weeks

• Change From Baseline in Daytime maSBP and maDBP

  Baseline, 8 weeks

• Change From Baseline in Nighttime maSBP and maDBP

  Baseline and 8 weeks

• Change From Baseline in Mean Sitting Pulse Pressure

  Baseline, 8 weeks

Study Arms (7)

VAL + AHU 400 mg

EXPERIMENTAL

Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.

Drug: Valsartan; Drug: AHU377

VAL + AHU 200 mg

EXPERIMENTAL

Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.

Drug: Valsartan; Drug: AHU377

VAL + AHU 100 mg

EXPERIMENTAL

Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.

Drug: Valsartan; Drug: AHU377

VAL + AHU 50 mg

EXPERIMENTAL

Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.

Drug: Valsartan; Drug: AHU377

VAL 320 mg

EXPERIMENTAL

Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.

Drug: Valsartan

LCZ 400 mg

EXPERIMENTAL

Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.

Drug: LCZ696

Placebo

EXPERIMENTAL

Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.

Drug: Placebo

Interventions

LCZ696 DRUG

LCZ696 was supplied as tablets in blister cards in 100 mg strengths.

LCZ 400 mg

Valsartan DRUG

Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.

VAL + AHU 100 mg; VAL + AHU 200 mg; VAL + AHU 400 mg; VAL + AHU 50 mg; VAL 320 mg

AHU377 DRUG

AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.

VAL + AHU 100 mg; VAL + AHU 200 mg; VAL + AHU 400 mg; VAL + AHU 50 mg

Placebo DRUG

Placebo was supplied as tablets in blister cards.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (90)

Novartis Investigative Site

Clearwater, Florida, 33756, United States

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Novartis Investigative Site

Chicago, Illinois, 60607, United States

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Novartis Investigative Site

Chicago, Illinois, 60610, United States

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Novartis Investigative Site

Metairie, Louisiana, 70006, United States

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Novartis Investigative Site

Belzoni, Mississippi, 39038, United States

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Novartis Investigative Site

Jackson, Mississippi, 39202, United States

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Novartis Investigative Site

Jackson, Mississippi, 39209, United States

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Novartis Investigative Site

St Louis, Missouri, 63031, United States

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Novartis Investigative Site

St Louis, Missouri, 63141, United States

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Novartis Investigative Site

Henderson, Nevada, 89014, United States

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Novartis Investigative Site

Las Vegas, Nevada, 89119, United States

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Novartis Investigative Site

Buffalo, New York, 14215, United States

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Novartis Investigative Site

Charlotte, North Carolina, 28277, United States

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Novartis Investigative Site

Greensboro, North Carolina, 27401, United States

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Novartis Investigative Site

Greensboro, North Carolina, 27408, United States

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Novartis Investigative Site

Shelby, North Carolina, 28152, United States

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Novartis Investigative Site

Erie, Pennsylvania, 16509, United States

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Novartis Investigative Site

Bryan, Texas, 77802, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

Buenos Aires, Buenos Aires, C1120AAC, Argentina

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Novartis Investigative Site

Caba, Buenos Aires, C1440AAD, Argentina

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Novartis Investigative Site

Lanús, Buenos Aires, B8000XAV, Argentina

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Novartis Investigative Site

Caba, Buenos Aires F.D., C1179AAB, Argentina

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Novartis Investigative Site

Corrientes, Corrientes Province, W3400, Argentina

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Novartis Investigative Site

Córdoba, Córdoba Province, X5003DCP, Argentina

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Novartis Investigative Site

Rosario, Santa Fe Province, S2000AII, Argentina

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Novartis Investigative Site

Rosario, Santa Fe Province, S200CXP, Argentina

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Novartis Investigative Site

San Miguel de Tucumán, Tucumán Province, T4000EBR, Argentina

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Novartis Investigative Site

Mount Pearl, Newfoundland and Labrador, A1N 1W7, Canada

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Novartis Investigative Site

Mirabel, Quebec, J7J 2K8, Canada

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Novartis Investigative Site

Ste-Foy, Quebec, G1V 4G2, Canada

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Novartis Investigative Site

Csongrád, Hungary, 6640, Hungary

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Novartis Investigative Site

Érd, Hungary, H-2030, Hungary

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Novartis Investigative Site

Budapest, 1045, Hungary

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Novartis Investigative Site

Budapest, 1136, Hungary

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Novartis Investigative Site

Miskolc, 3525, Hungary

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Novartis Investigative Site

Miskolc, 3530, Hungary

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Novartis Investigative Site

Nyiregyháza, 4400, Hungary

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Novartis Investigative Site

Szeged, H-6720, Hungary

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Novartis Investigative Site

Törökbálint, 2045, Hungary

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Novartis Investigative Site

Visakhapatnam, Andhra Pradesh, 530002, India

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Novartis Investigative Site

Ahmedabad, Gujarat, 380 051, India

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Novartis Investigative Site

Nashik, Maharashtra, 422 005, India

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Novartis Investigative Site

Nashik, Maharashtra, 422005, India

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Novartis Investigative Site

Pune, Maharashtra, 411005, India

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Novartis Investigative Site

Ludhiana, Punjab, 141002, India

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Novartis Investigative Site

Jaipur, Rajasthan, 302016, India

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Novartis Investigative Site

Lucknow, Uttar Pradesh, 226003, India

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Novartis Investigative Site

Lucknow, Uttar Pradesh, 226005, India

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Novartis Investigative Site

Bucharest, District 1, 011422, Romania

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Novartis Investigative Site

Bucharest, District 1, 012064, Romania

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Novartis Investigative Site

Bucharest, District 1, Romania

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Novartis Investigative Site

Bucharest, District 2, 021705, Romania

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Novartis Investigative Site

Oradea, Jud. Bihor, 410032, Romania

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Novartis Investigative Site

Craiova, Jud. Dolj, 200147, Romania

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Novartis Investigative Site

Bucharest, 060011, Romania

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Novartis Investigative Site

Nitra, Slovak Republic, 949 01, Slovakia

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Novartis Investigative Site

Prešov, Slovak Republic, 08001, Slovakia

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Novartis Investigative Site

Bratislava, Slovakia, 831 06, Slovakia

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Novartis Investigative Site

Liptovský Mikuláš, Slovakia, 031 01, Slovakia

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Novartis Investigative Site

Nitra, Slovakia, 949 01, Slovakia

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Novartis Investigative Site

Nitra, Slovakia, 94901, Slovakia

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Novartis Investigative Site

Nové Zámky, Slovakia, 940 01, Slovakia

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Novartis Investigative Site

Partizánske, Slovakia, 958 01, Slovakia

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Novartis Investigative Site

Prešov, Slovakia, 080 01, Slovakia

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Novartis Investigative Site

Prešov, Slovakia, 081 01, Slovakia

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Novartis Investigative Site

Ružomberok, Slovakia, 034 26, Slovakia

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Novartis Investigative Site

Sereď, Slovakia, 926 00, Slovakia

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Novartis Investigative Site

Šaľa, Slovakia, 927 03, Slovakia

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Novartis Investigative Site

Zvolen, Slovakia, 960 01, Slovakia

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Novartis Investigative Site

Bucheon-si, Gyeonggi-do, 424-717, South Korea

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Novartis Investigative Site

Goyang-si, Gyeonggi-do, 411-706, South Korea

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Novartis Investigative Site

Uijeongbu-si, Gyeonggi-do, 480-717, South Korea

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Novartis Investigative Site

Seoul, Korea, 05505, South Korea

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Novartis Investigative Site

Seoul, Korea, 137-701, South Korea

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Novartis Investigative Site

Seoul, Korea, 152-703, South Korea

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Novartis Investigative Site

Koyang, Kyunggi, 410-719, South Korea

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Novartis Investigative Site

Seoul, Seoul, 140-743, South Korea

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Novartis Investigative Site

Seoul, Seoul, 150-713, South Korea

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Novartis Investigative Site

Seoul, 150-950, South Korea

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Novartis Investigative Site

Granada, Andalusia, 18012, Spain

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Novartis Investigative Site

Seville, Andalusia, 41009, Spain

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Novartis Investigative Site

Badalona, Catalonia, 08914, Spain

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Novartis Investigative Site

Centelles, Catalonia, 08540, Spain

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Novartis Investigative Site

Tarragona, Catalonia, 43350, Spain

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Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

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Novartis Investigative Site

Madrid, Madrid, 28046, Spain

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Novartis Investigative Site

Alicante, Valencia, 03004, Spain

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Novartis Investigative Site

Alzira, Valencia, 46600, Spain

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Novartis Investigative Site

Barcelona, Spain

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MeSH Terms

Conditions

Isolated Systolic Hypertension; Hypertension

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan; sacubitril

Condition Hierarchy (Ancestors)

Essential Hypertension; 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

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

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: January 20, 2011
• First Posted: January 21, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 29, 2016
• Results First Posted: August 18, 2015

Record last verified: 2015-12

Locations

KR (10); US (19); AR (9); CA (3); SL (14); IN (9); ES (10); HU (9); RO (7)