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

Systolic Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01281306
• Other study ID #: CLCZ696A2223
• Secondary ID: 2010-022326-32
• Status: Completed
• Phase: Phase 2
• First received: January 20, 2011
• Last updated: December 22, 2015
• Start date: January 2011
• Est. completion date: December 2011

Study information

• Verified date: December 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Human Research Bioethics CommitteeCanada: Therapeutic Products Directorate at Health CanadaHungary: National Institute of PharmacyIndia: Drugs Controller General of IndiaPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Agency of Medicine (Agentia Nationala a Medicamentului)South Korea: Korea Food and Drug Administration (KFDA)Slovakia: State Institute for Drug ControlSpain: Agencia Espanola del Medicamento y Productos Sanitarios (AEMPS)
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 910
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Systolic Hypertension

Intervention

Drug:
• LCZ696
LCZ696 was supplied as tablets in blister cards in 100 mg strengths.
• Valsartan
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
• AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
• Placebo
Placebo was supplied as tablets in blister cards.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos aires
Argentina	Novartis Investigative Site	Caba	Capital Federal
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Corrientes
Argentina	Novartis Investigative Site	Lanus	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Canada	Novartis Investigative Site	Mirabel	Quebec
Canada	Novartis Investigative Site	Mount Pearl	Newfoundland and Labrador
Canada	Novartis Investigative Site	Ste-Foy	Quebec
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Csongrad
Hungary	Novartis Investigative Site	Erd
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Nyiregyháza
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Torokbalint
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Ludhiana	Punjab
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Vishakhapatnam	Andhra Pradesh
Korea, Republic of	Novartis Investigative Site	Bucheon	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Goyang	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Koyang	Kyunggi
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Uijeongbu-Si	Gyeonggi-do
Romania	Novartis Investigative Site	Bucharest	District 1
Romania	Novartis Investigative Site	Bucharest	District 1
Romania	Novartis Investigative Site	Bucharest	District 1
Romania	Novartis Investigative Site	Bucharest	District 2
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Craiova	Jud. Dolj
Romania	Novartis Investigative Site	Oradea	Jud. Bihor
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Liptovsky Mikulas
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Nitra	Slovak Republic
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Partizanske
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Presov	Slovak Republic
Slovakia	Novartis Investigative Site	Ruzomberok
Slovakia	Novartis Investigative Site	Sala
Slovakia	Novartis Investigative Site	Sered
Slovakia	Novartis Investigative Site	Zvolen
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Alzira	Comunidad Valenciana
Spain	Novartis Investigative Site	Badalona	Cataluña
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Centelles	Cataluña
Spain	Novartis Investigative Site	Granada	Andalucia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Tarragona	Cataluña
United States	Novartis Investigative Site	Belzoni	Mississippi
United States	Novartis Investigative Site	Bryan	Texas
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Erie	Pennsylvania
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Henderson	Nevada
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Metairie	Louisiana
United States	Novartis Investigative Site	Shelby	North Carolina
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Hungary,  India,  Korea, Republic of,  Romania,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change From Baseline in Mean Diastolic Blood Pressure (msDBP)	Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP)	Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Daytime maSBP and maDBP	Twenty four hour ABPM was performed twice during the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Nighttime maSBP and maDBP	Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.	Baseline and 8 weeks	No
Secondary	Change From Baseline in Mean Sitting Pulse Pressure	Pulse rate measurements were performed. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in Mean Ambulatory Pulse Pressure	Pulse rate measurements were performed. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in maSBP and maDBP in Dippers	Twenty four hour ABPM was performed twice during the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in maSBP and maDBP in Non-dippers	Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age	Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age	Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age	Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age	Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.	Baseline, 8 weeks	No
Secondary	Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response	Sitting BP measurements were performed at trough (23-26 hours post-morning dose). Blood pressure control was defined as msSBP/MSDBP < 140/90 mmHg. Blood pressure response in msSBP was defined as <140 mmHg or a reduction >= 20mmHg from baseline. Blood pressure response in msDBP was defined as < 90 mmHg or a reduction >= 10 mmHg from baseline.	8 weeks	No
Secondary	Number of Participants With Adverse Events, Serious Adverse Events and Death	Adverse event monitoring was conducted throughout the study.	8 weeks	Yes