Substantial Amendment 1 (dated 28 January 2014) to the protocol was issued before any patient was enrolled into the study. The amendments were as follows: - The requirement for patients to have had at least 4 prescriptions of Seretide® 250 Evohaler® in the last 6 months before screening was removed; it was only required that the patient be on Seretide® 250 Evohaler® for the last 6 months before screening. The minimum number of prescriptions was initially set to at least 4 with the aim of ensuring adherence to treatment prior to study. However, this was removed given that the number of inhalers prescribed is unlikely to be a very accurate estimator of adherence. - Inclusion criteria “Step 4 of the British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) guidelines” was removed as patients who are on Seretide® 250 Evohaler® are by definition at Step 4. - While ACQ7<1.5 was not listed in the inclusion criteria, this criterion was erroneously mentioned elsewhere in the protocol text and was removed to be consistent with the inclusion criteria listed. - In Appendix C: “Actuation not corresponding with inhalation; actuation before inhalation or too late after inhalation (more than 2 seconds)” was erroneously listed as an error when using a spacer. This has been corrected. - For randomisation to both Phase 1 and Phase 2, number of exacerbations in the 12 months prior to Phase 1 was considered; in the protocol version 1.0, it was erroneously stated that, for Phase 2 randomisation, the number of exacerbations in the 12 months before Phase 2 would be considered.

Substantial Amendment 2 (dated 17 November 2014) to the protocol was issued after 23 patients had been enrolled into the study. It included both substantial and non-substantial changes to the protocol, as follows: - Substantial amendment to increase compensation to patients from £20 to £25/visit - Non-substantial change of wording from “nurse” to “healthcare professional” in protocol and other relevant study documents to reflect that both nurses and pharmacists were recruiting patients and conducting clinics for the study - A dedicated phone-line and website was set up for patients to express interest There was no impact on the patients already enrolled into the study and this Amendment did not result in any changes that would impact outcomes or analyses of data.