Second round CER report: 9 October 2015 AusPAR Attachment 2 Extract from the Clinical Evaluation Report for sacubitril / valsartan salt complex Proprietary Product Name: Entresto / Novartis sacubitril/valsartan Sponsor: Novartis Pharmaceuticals Australia Pty Ltd About the Therapeutic Goods Administration (TGA) The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health, and is responsible for regulating medicines and medical devices. The TGA administers the Therapeutic Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary. The work of the TGA is based on applying scientific and clinical expertise to to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. To report a problem with a medicine or medical device, please see the information on the TGA website <>. the Extract from the Clinical Evaluation Report
ANCOVA analysis of covariance ANP Atrial-derived natriuretic peptides ARB Angiotensin receptor blockers ARNI Angiotensin receptor neprilysin inhibitor AST Aspartate aminotransferase AT1 Angiotensin type 1 AUC Area under the serum concentration-time curve AUC0-t Area the serum concentration-time curve from time zero to time t AUCinf Area the serum concentration-time curve from time zero to infinity AUClast Area Under the Plasma Concentration-time profile from time zero to the time of the last quantifiable concentration AUCtau Area under the plasma concentration-time curve for a dosing interval AUEC Area under the effect curve Aβ Amyloid beta peptides BID Bis in die / Twice a day BMI body mass index BNP brain natriuretic peptide BP blood pressure CABG coronary artery bypass CAD coronary artery disease CCS clinical composite score cGMP Cyclic guanosine monophosphate CHF congestive heart failure CI Confidence interval trial trial
GCP Good Clinical Practice GMR Goemetric mean ratio glycosylated haemoglobin HCTZ Hydrochlorothiazide HF Heart Failure Heart failure with preserved ejection fraction HFrEF Heart failure with reduced ejection fraction HTN hypertension IC50 Concentration leading to 50% inhibition INR International normalised ratio ITT intent to treat (population) iv Intravenous(ly) IVRS Interactive Response System KCCQ Kansas City Cardiomyopathy Questionnaire LAVI left atrial volume index sacubitrilat Active moiety of AHU377 LCZ696 r the sacubitril/valsartan combination LFT Liver function test LHFQ Living with Heart Failure Questionnaire LLN limit of normal LSM least squares mean LVEDP left ventricular end diastolic pressure LVEDV left ventricular end diastolic volume LVEF left ventricular ejection fraction LVESV left ventricular end systolic volume
SSH Salt sensitive hypertension T1/2 Estimated terminal half-life TEAE treatment emergent adverse event TIA transient ischaemic attack Tmax Time to maximal drug concentration TR tricuspid regurgitation ULN upper limit of normal Vz/F Apparent volume of distribution during terminal phase (associated with λZ corrected for bioavailability) WBC white blood cells WHO World Health Organisation