auspar-thyroxine-sodium-140612

Australian Public Assessment Report for Thyroxine Sodium Proprietary Product Name: Eltroxin, Aspen Thyroxine, Thyroxine Aspen June 2014

Therapeutic Goods Administration Sponsor: Aspen Pharma Pty Ltd AusPAR Eltroxin, Aspen Thyroxine, Thyroxine Aspen Thyroxine Sodium Aspen Pharma Pty Ltd PM-2012-04477-1-5 Final 12 June 2014 Page 2 of 41

Therapeutic Goods Administration 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 Goods 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 decision- making, 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 < http://www.tga.gov.au >. About AusPARs  An Australian Public Assessment Record (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission.  AusPARs are prepared and published by the TGA.  An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations, and extensions of indications.  An AusPAR is a static document, in that it will provide information that relates to a submission at a particular point in time.  A new AusPAR will be developed to reflect changes to indications and/or major variations to a prescription medicine subject to evaluation by the TGA. Copyright © Commonwealth of Australia 2014 This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to < tga.copyright@tga.gov.au >. AusPAR Eltroxin, Aspen Thyroxine, Thyroxine Aspen Thyroxine Sodium Aspen Pharma Pty Ltd PM-2012-04477-1-5 Final 12 June 2014 Page 3 of 41

Therapeutic Goods Administration Contents List of commonly used abbreviations_______________________________________5 I. Introduction to product submission______________________________________6 Submission details_____________________________________________________________________6 Product background___________________________________________________________________6 Regulatory status______________________________________________________________________7 Product Information___________________________________________________________________8 II. Quality findings______________________________________________________________8 Introduction____________________________________________________________________________8 Drug substance (active ingredient)___________________________________________________8 Drug product___________________________________________________________________________9 Biopharmaceutics____________________________________________________________________10 Advisory committee considerations________________________________________________11 Quality summary and conclusions__________________________________________________11 III. Nonclinical findings______________________________________________________12 IV. Clinical findings___________________________________________________________12 Introduction__________________________________________________________________________12 Pharmacokinetics____________________________________________________________________12 Pharmacodynamics__________________________________________________________________14 Dosage selection for the pivotal studies____________________________________________14 Efficacy________________________________________________________________________________14 Safety__________________________________________________________________________________14 First round benefit-risk assessment________________________________________________16 First round recommendation regarding authorisation____________________________16 Clinical questions_____________________________________________________________________16 Second round evaluation of clinical data submitted in response to questions___17 V. Pharmacovigilance findings______________________________________________21 Risk management plan_______________________________________________________________21 VI. Overall conclusion and risk/benefit assessment____________________25 Consideration of the strengths proposed___________________________________________25 Quality_________________________________________________________________________________29 Nonclinical____________________________________________________________________________29 Clinical________________________________________________________________________________29 Risk management plan_______________________________________________________________31 Risk-benefit analysis_________________________________________________________________31 Outcome_______________________________________________________________________________39

Therapeutic Goods Administration Attachment 1. Product Information_______________________________________40 Attachment 2. Extract from the Clinical Evaluation Report____________40