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: July 21, 2015
Last verified: July 2015
  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: Valsartan
Drug: AHU377
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:
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.


Secondary Outcome Measures:
  • Change From Baseline in Mean Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.

  • Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Daytime maSBP and maDBP [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Nighttime maSBP and maDBP [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Mean Sitting Pulse Pressure [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Pulse rate measurements were performed. A negative change from baseline indicates improvement.

  • Change From Baseline in Mean Ambulatory Pulse Pressure [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Pulse rate measurements were performed. A negative change from baseline indicates improvement.

  • Change From Baseline in maSBP and maDBP in Dippers [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in maSBP and maDBP in Non-dippers [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.

  • Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.

  • Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events, Serious Adverse Events and Death [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Adverse event monitoring was conducted throughout the study.


Enrollment: 915
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: VAL + AHU 400 mg
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
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL + AHU 200 mg
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
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL + AHU 100 mg
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
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL + AHU 50 mg
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
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL 320 mg
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
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
Experimental: LCZ 400 mg
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
LCZ696 was supplied as tablets in blister cards in 100 mg strengths.
Experimental: Placebo
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Drug: Placebo
Placebo was supplied as tablets in blister cards.

  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

  Show 90 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
Results First Received: July 21, 2015
Last Updated: July 21, 2015
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
Cardiovascular Diseases
Vascular Diseases
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015