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 .
About the Extract from the Clinical Evaluation Report
This document provides a more detailed evaluation of the clinical findings, extracted from the Clinical Evaluation Report (CER) prepared by the TGA. This extract does not include sections from the CER regarding product documentation or post market activities.
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 .
List of common abbreviations 6
1Submission details 11
1.1Identifying information 11
1.2Drug class and therapeutic indication 11
1.3Dosage forms and strengths 11
1.4Dosage and administration 11
2.1Information on the condition being treated 14
2.2 Current treatment options 15
2.3Clinical rationale 17
2.4 Formulation 18
2.5Regulatory history 19
2.6Guidance and references used 22
2.7Evaluator’s commentary on the background information 23
3Contents of the clinical dossier 23
3.1Scope of the clinical dossier 23
3.2Paediatric data 26
3.3Good clinical practice 26
3.4Evaluator’s commentary on the clinical dossier 26
4.1Studies providing pharmacokinetic information 27
4.2Pharmacokinetics in healthy subjects 30
4.3Evaluator’s overall conclusions on pharmacokinetics 40
5.1Studies providing pharmacodynamic information 45
5.2Summary of pharmacodynamics 45
5.3Pharmacodynamic effects 47
5.4Evaluator’s overall conclusions on pharmacodynamics 52
5.5Clinical Pharmacology questions 54
6Dosage selection for the pivotal studies 55
6.1Pharmacokinetics and pharmacodynamics: dose finding studies 55
6.2Phase II dose finding studies 56
6.3Phase III pivotal studies investigating more than one dose regimen 56
7Clinical efficacy 56
7.1Studies providing evaluable efficacy data 56
7.2Pivotal or main efficacy studies 57
7.3Analyses performed across trials: pooled and meta analyses 138
7.4Evaluator’s conclusions on clinical efficacy 138
8Clinical safety 139
Comment and clinical question: 139
8.1Studies providing evaluable safety data 143
8.2Studies that assessed safety as the sole primary outcome 146
8.3Patient exposure (taken from 90-day safety update for Study 1023, Top-line summary for Study 1008) 146
8.4Adverse events 150
8.5Evaluation of issues with possible regulatory impact 199
8.6Other safety issues 208
8.7Post marketing experience 209
8.8Evaluator’s overall conclusions on clinical safety 211
9First round benefit-risk assessment 213
9.1First round assessment of benefits 213
9.2First round assessment of risks 214
9.3First round assessment of benefit-risk balance 215
10 First round recommendation regarding authorisation 215