Recent Updates
Recently added Catalysts

LCZ696

Phase 3

Hypertension | Small molecule | Cardiovascular |Novartis AG|Last Updated: May 4, 2016

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
Premium
Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
Premium
Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials6
Total Enrollment2,683
FDA Designations
No designations recorded
Clinical Trials (6)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01876368Efficacy and Safety of LCZ696 Compared to Olmesartan in Essential Hypertensive Patients Not Responsive to OlmesartanPHASE3 COMPLETED 376Sep 1, 2013Aug 1, 2014Dec 7, 201551 United States, Argentina +5
NCT01692301Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With HypertensionPHASE2 COMPLETED 454Dec 1, 2012Apr 1, 2015May 4, 201647 United States, Argentina +10
NCT01631864Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive SubjectsPHASE2 COMPLETED 98Oct 1, 2012Jul 1, 2013Aug 10, 20153 Germany, Netherlands
NCT01353508Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy VolunteersPHASE2 COMPLETED 32Mar 1, 2011Aug 1, 2012Nov 23, 20151 Russia
NCT01193101Efficacy and Safety of LCZ696 Compared to Placebo in Patients With Essential HypertensionPHASE2 COMPLETED 389Aug 1, 2010Apr 1, 2011Feb 15, 201634 China, Japan +3
NCT00549770Efficacy and Safety of LCZ696A in Patients With Essential HypertensionPHASE2 COMPLETED 1,334Sep 1, 2007Jul 1, 2008Aug 25, 2015182 United States, Argentina +16
Unlock Drug Trial Details
Study Endpoints
Primary Endpoints
Change From Baseline in 24-hour Mean Ambulatory Systolic Blood Pressure (maSBP)
baseline, 8 weeks

Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The first 24-hour ABPM will be performed beginning at 24 hours prior to baseline visit and the second will be performed 24 hours prior to week 8 visit.

Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks
baseline, 12 weeks

Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software. At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.

Change From Baseline in Insulin Sensitivity Index
baseline, 8 weeks

The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.

24-hour Urinary Sodium Excretion
day 1

Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).

Cumulative 7-day Urinary Sodium Excretion
7 day-cummulative (days 1 through 7)

Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).

Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Baseline, 8 weeks

Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.

Secondary Endpoints
Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (maDBP)
baseline, 8 weeks
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
baseline, 8 weeks
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
baseline, 8 weeks
Unlock Study Endpoints
Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
LCZ696 200 mgEXPERIMENTALPatients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.
Olmesartan 20 mgACTIVE_COMPARATORPatients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.
LCZ696 (sacubitril/valsartan)EXPERIMENTALRandomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
OlmesartanACTIVE_COMPARATORRandomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
LCZ696EXPERIMENTALLCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipineACTIVE_COMPARATORamlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
LCZ696 to Valsartan - Heart Failure (HF) cohortEXPERIMENTALParticipants in this arm received Valsartan 160 mg twice daily (bid) during open-label run-in, LCZ696 200 mg bid double blind treatment during period 1, Valsartan 160 mg bid during wash-out, and Valsartan 160 mg bid double blind treatment during period 2.
Valsartan to LCZ696 - HF CohortEXPERIMENTALParticipants in this arm received Valsartan 160 mg twice daily bid during open-label run-in, Valsartan 160 mg bid during period 1, Valsartan 160 mg bid during wash-out, and LCZ696 200 mg bid double blind treatment during period 2.
LCZ696 to Valsartan - Hypertension (HTN) cohortEXPERIMENTALParticipants in this arm received Valsartan 320 mg once daily (qd) during open-label run-in, LCZ696 400 mg qd double blind treatment during period 1, Valsartan 320 mg qd during wash-out, and Valsartan 320 mg qd double blind treatment during period 2.
Valsartan to LCZ696 - HTN cohortEXPERIMENTALParticipants in this arm received Valsartan 320 mg qd during open-label run-in, Valsartan 320 mg qd during period 1, Valsartan 320 mg qd during wash-out, and LCZ696 400 qd bid double blind treatment during period 2.
LCZ696 100 mgEXPERIMENTALLCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
LCZ696 400 mgEXPERIMENTALLCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
PlaceboPLACEBO_COMPARATORPlacebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
Valsartan 80 mgACTIVE_COMPARATORParticipants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 160 mgACTIVE_COMPARATORParticipants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 320 mgACTIVE_COMPARATORParticipants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
AHU377 200 mgEXPERIMENTALParticipants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
Interventions
NameTypeDescription
LCZ696DRUG -
OlmesartanDRUG -
Placebo of LCZ696DRUG -
Placebo of OlmesartanDRUG -
LCZ696 matching placeboDRUGLCZ696 Matching Placebo tablet
Olmesartan matching placeboDRUGOlmesartan matching placebo capsule
amlodipineDRUGamlodipine 2.5 mg or 5 mg tablets
hydrochlorothiazideDRUGhydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets
PlaceboDRUGMatching placebo to LCZ696 and amlodipine.
ValsartanDRUG160 mg tablets
AHU377DRUG -
Unlock Study Design Details
Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites51

Inclusion Criteria: * patients with mild to moderate hypertension, untreated or currently taking antihypertensive therapy * treated patients (using antihypertensive drugs within 4 weeks prior to first visit) must have an office msSBP ≥ 145 mmHg and \< 180 mmHg after washout epoch and after 4 weeks ...

Countries:United StatesArgentinaGuatemalaPhilippinesPuerto RicoRussiaSpainColombiaFranceGermanyGreeceItalyJapanSouth KoreaTaiwanNetherlandsChinaThailandCanadaDenmarkFinlandHungaryLatviaLithuaniaPolandSlovakiaSweden
Unlock Eligibility Criteria