Cover Page for Protocol Sponsor name: Novo Nordisk A/S NCT number NCT02501161 Sponsor trial ID: NN9068-4228 Official title of study: A 104 week clinical trial comparing long term glycaemic control of insulin degludec/liraglutide (IDegLira) versus insulin glargine therapy in subjects with type 2 diabetes mellitus (DUAL™ VIII) Document date: 01 March 2019 IDegLira Date: 01 March 2019 Novo Nordisk Trial ID: NN9068-4228 Version: 1.0 CONFIDENTIAL Clinical Trial Report Status: Final Appendix 16.1.1 16.1.1 Protocol and protocol amendments List of contents Protocol ............................................................................................................................................... Link Appendix A ......................................................................................................................................... Link Appendix B................................................................................................ .......................................... Link Attachment I and II............................................................................................................................ Link Protocol amendment 1 - MX ................................................................ ............................................. Link Protocol amendment 2 - NO.............................................................................................................. Link Protocol amendment 3 - Global/HQ ................................................................................................. Link Protocol amendment 4 - Global/HQ ................................................................................................. Link Redacted protocol Includes redaction of personal identifiable information only. Protocol Date: 10 July 2015 Novo Nordisk Trial ID: NN9068-4228 Version: 1.0 CONFIDENTIAL UTN: U1111-1165-3914 Status: Final EudraCT no.: 2014-005639-15 Page: 1 of 95 Protocol Trial ID: NN9068-4228 DUALTM VIII – Durability A 104 week clinical trial comparing long term glycaemic control of insulin degludec/liraglutide (IDegLira) versus insulin glargine therapy in subjects with type 2 diabetes mellitus Trial phase: 3b Protocol originator This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant parties. disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant parties. Protocol Date: 10 July 2015 Novo Nordisk Trial ID: NN9068-4228 Version: 1.0 CONFIDENTIAL UTN: U1111-1165-3914 Status: Final EudraCT no.: 2014-005639-15 Page: 2 of 95 Table of Contents Page Table of Contents..............................................................................................................................................2 List of abbreviations.........................................................................................................................................6 1 Summary....................................................................................................................................................8 2 Flow chart ................................................................................................................................................11 3 Background information and rationale for the trial............................................................................15 3.1 Background information..............................................................................................................15 3.2 Rationale for the trial ...................................................................................................................16 4 Objectives and endpoints........................................................................................................................17 4.1 Objectives ....................................................................................................................................17 4.2 Endpoints .....................................................................................................................................17 4.2.1 Primary endpoint........................................................................................................17 4.2.2 Secondary endpoints..................................................................................................17 4.2.2.1 Supportive secondary endpoints..........................................................17 5 Trial design ..............................................................................................................................................20 5.1 Type of trial .................................................................................................................................20 5.2 Rationale for trial design..............................................................................................................20 5.3 Treatment of subjects...................................................................................................................21 5.4 Treatment after discontinuation of trial product ..........................................................................21 5.5 Rationale for treatment ................................................................................................................22 6 Trial population.......................................................................................................................................23 6.1 Number of subjects ......................................................................................................................23 6.2 Inclusion criteria ..........................................................................................................................23 6.3 Exclusion criteria .........................................................................................................................23 6.4 Premature discontinuation of trial product ..................................................................................25 6.4.1 Rescue criteria............................................................................................................25 6.5 Withdrawal of consent.................................................................................................................26 6.6 Subject replacement.....................................................................................................................26 6.7 Rationale for trial population.......................................................................................................26 7 Milestones.................................................................................................................................................27 8 Methods and assessments .......................................................................................................................28 8.1 Visit procedures ...........................................................................................................................28 8.1.1 Fasting requirements..................................................................................................28 8.1.2 Screening (visit 1)......................................................................................................28 8.1.3 Randomisation (visit 2)..............................................................................................29 8.1.4 Treatment initiation and titration ...............................................................................30 8.1.5 Diaries........................................................................................................................31 8.1.6 Follow up visits (visit 14 and 15) ..............................................................................33 8.1.7 Unscheduled visits .....................................................................................................33 8.1.8 Premature discontinuation of trial product ................................................................33 8.1.9 Withdrawal of consent...............................................................................................34 8.2 Subject related information..........................................................................................................34 Protocol Date: 10 July 2015 Novo Nordisk Trial ID: NN9068-4228 Version: 1.0 CONFIDENTIAL UTN: U1111-1165-3914 Status: Final EudraCT no.: 2014-005639-15 Page: 3 of 95 8.2.1 Concomitant illness and medical history ...................................................................34 8.2.2 Concomitant medication............................................................................................35 8.2.3 Smoking status (Tobacco use) ...................................................................................35 8.3 Assessments for efficacy..............................................................................................................36 8.3.1 Self-measured plasma glucose...................................................................................36 8.4 Assessments for safety.................................................................................................................37 8.4.1 Hypoglycaemic episodes