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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
History of Changes
  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:

Drug Information available for: Valsartan
U.S. FDA Resources

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

  Show 91 Study Locations
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
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013