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
- Conditions
- Systolic Hypertension
- Interventions
- Registration Number
- NCT01281306
- Lead Sponsor
- Novartis Pharmaceuticals
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 910
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks. VAL + AHU 100 mg AHU377 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. LCZ 400 mg LCZ696 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. VAL + AHU 50 mg AHU377 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. VAL + AHU 200 mg AHU377 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. VAL + AHU 400 mg AHU377 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. VAL + AHU 400 mg Valsartan 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. VAL + AHU 200 mg Valsartan 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. VAL + AHU 100 mg Valsartan 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. VAL + AHU 50 mg Valsartan 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. VAL 320 mg Valsartan 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Baseline, 8 weeks Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Mean Sitting Pulse Pressure Baseline, 8 weeks Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Change From Baseline in maSBP and maDBP in Non-dippers Baseline, 8 weeks 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 Mean Diastolic Blood Pressure (msDBP) Baseline, 8 weeks 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) Baseline, 8 weeks 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 Baseline, 8 weeks 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 Baseline and 8 weeks 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 Ambulatory Pulse Pressure Baseline, 8 weeks Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age Baseline, 8 weeks 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 msSBP and msDBP in Participants < 65 Years of Age Baseline, 8 weeks 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 Baseline, 8 weeks 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 Dippers Baseline, 8 weeks 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.
Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response 8 weeks 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.
Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age Baseline, 8 weeks 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 With Adverse Events, Serious Adverse Events and Death 8 weeks Adverse event monitoring was conducted throughout the study.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇪🇸Madrid, Spain