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: December 22, 2015
Last verified: December 2015

January 20, 2011
December 22, 2015
January 2011
December 2011   (final data collection date for primary outcome measure)
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.
reduction in mean sitting systolic blood pressure (msSBP) [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01281306 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
Not Provided
Not Provided
 
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
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
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).
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Systolic Hypertension
  • Drug: LCZ696
    LCZ696 was supplied as tablets in blister cards in 100 mg strengths.
  • 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.
  • Drug: Placebo
    Placebo was supplied as tablets in blister cards.
  • 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.
    Interventions:
    • Drug: Valsartan
    • Drug: AHU377
  • 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.
    Interventions:
    • Drug: Valsartan
    • Drug: AHU377
  • 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.
    Interventions:
    • Drug: Valsartan
    • Drug: AHU377
  • 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.
    Interventions:
    • Drug: Valsartan
    • Drug: AHU377
  • 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.
    Intervention: Drug: Valsartan
  • 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.
    Intervention: Drug: LCZ696
  • Experimental: Placebo
    Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
910
December 2011
December 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Canada,   Hungary,   India,   Korea, Republic of,   Romania,   Slovakia,   Spain
Poland
 
NCT01281306
CLCZ696A2223, 2010-022326-32
Not Provided
Not Provided
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP