This protocol amendment has been created predominantly to extend the duration of the study from 12 weeks to 24 weeks for subjects enrolled across all study sites in Germany. For these subjects, blinded treatment will continue for a further 12 weeks from the end of the initial 12 week treatment period. The data analysis and statistical considerations section of the protocol (Section 8) has been amended to include a new Intent-To-Treat (ITT) population for Germany and also to revise statistical considerations with regards to the analysis of additional data (St. George’s Respiratory Questionnaire [SGRQ], Chronic Obstructive Pulmonary Disease Assessment Test [CAT], rescue medication use and safety) for those subjects enrolled in Germany. Exclusion criterion number 6 has been revised to exclude subjects with both moderate and severe renal impairment (as opposed to severe renal impairment only) unless in the opinion of the investigator, the benefit is likely to outweigh the risk in accordance with the tiotropium label (SmPC; Summary of Product Characteristics). The medical monitor contact information has been revised to include two new medical monitors responsible for specific regions. New text has been included with regards to recent approvals of the UMEC monotherapy 62.5 mcg dose in Canada, USA and in Europe (European Economic Area). Other minor corrections and edits have been made.

The amendment has been created to clarify that a single dose from the nDPI will consist of 1 inhalation from the nDPI and that a single dose of tiotropium or matching placebo will consist of 2 inhalations of the powder contents of a single capsule with the Handihaler. • Thus the sections, 5.1 (paragraph 7), 5.1.2 (paragraph 1), 5.2 (paragraph 5) have been revised in alignment with the above mentioned text to clarify that a single dose from the nDPI will consist of 1 inhalation from the nDPI and that a single dose of tiotropium or matching placebo will consist of 2 inhalations of the powder contents of a single capsule with the Handihaler. Also, Section 5.2 (paragraph 8) has been revised to clarify that an albuterol/salbutamol new container will be dispensed “as needed after Visit 1”. Also, the following revisions are included to revise the medical monitor information, to clarify the calculation of compliance and to include the collection of pneumonia event specific information for pneumonia AEs in a specific Electronic Case Report Form (eCRF). The Disease Related Event (DRE) reporting in section 6.3.14 table was deleted as this is captured separately per explanation in Section 6.3.9: • The Medical Monitor information has been revised to update the global and add the new back-up Medical Monitors. • Section Protocol Summary has been revised for the primary endpoint to include formatting changes, second bullet formatting removed to reflect a single primary endpoint • Section 5.5 has been revised to clarify compliance with the Handihaler is to be determined by counting the number of “unused” capsules remaining • Section 6.3.7 has been added to include collection of pneumonia events specific information occurring after subject randomization in an eCRF. Section 6.3.14 has been revised to include pneumonia events for Prompt Reporting of Serious Adverse Events and Others Events to GlaxoSmithKline.