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

• 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 ]

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).

• Drug: LCZ696
  LCZ696 400 mg, LCZ696 200 mg
• Drug: AHU377
  AHU377 100 mg, AHU377 50 mg
• Drug: Valsartan
  Valsartan 320 mg, Valsartan 160 mg
• Drug: placebo

• 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
  Intervention: Drug: LCZ696
• 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
  Interventions:

  • Drug: AHU377
  • Drug: Valsartan
• 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
  Interventions:

  • Drug: AHU377
  • Drug: Valsartan
• 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
  Interventions:

  • Drug: AHU377
  • Drug: Valsartan
• 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
  Interventions:

  • Drug: AHU377
  • Drug: Valsartan
• 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
  Intervention: Drug: Valsartan
• Experimental: placebo
  patients will receive matching placebo for 8 weeks
  Intervention: Drug: placebo

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