This amendement was was applicable in all countries involved in the study. The main changes followed the coordinators’ opinion, and concerned mainly the modification of some selection / inclusion criteria.

This amendement was only applicable in Argentina, to comply with local regulation. A urinary pregnancy test was included at study entrance and then regularly, i.e. at all visits. Results had to be known before any dispensation of the study medication.

This amendement was applicable in all countries involved in the study. The main changes were: ­ For registration purpose, a 11-month double-blind follow-up extension period was added in order to collect 1 year safety data of a minimum of 100 patients treated with the highest doses of fixed-dose combination (Perindopril 10 mg / Indapamide 2.5 mg / Amlodipine 10 mg), and to confirm the sustained efficacy of this treatment over one year. Thus, a 4 month double-blind superiority study followed by a double-blind follow-up extension period until M15 were implemented instead of the 12-weeks double-blind period initially planned in the study protocol. The title, the objectives, and the design of the study were accordingly modified. ­ The design was adapted to keep the investigators and the Sponsor blinded with regard to the treatment group allocated to the patients over the efficacy / safety 4-month titration period and its follow-up extension. ­ - For safety reasons and to have a better follow-up of the patients over the 11-month extension period, HBPM measurements had been added for all patients in the study, and performed at M4 and M15. Moreover, for the patients who took part to the extension period, even if not involved in the sub-studies during the titration period, the ABPM was to be performed only at M15 during the week before the last visit with the objective to obtain the 24 hours profile. ­ - In order to detect possible differences between right and left arms, at the request of the investigators, it was decided to simplify the definition of the dominant arm for the BP measurement. At the first visit, the investigator was asked to take only 1 measurement of SBP and DBP (instead of 3) in supine position in both right and left arms. ­ - The 2013 ESH/ECS guidelines for management of arterial hypertension were implemented.

This amendement was only applicable in Ukraine in order to: postpone the Last Visit Last Patient (LVLP) date due to the extension of the recruitment period In accordance with the most recent quality information submitted to authorities, the storage conditions for the Therapeutic Units to be used in the study were included in this protocol version. No special storage was any more required. ­There was a discrepancy regarding the measurement time of the complete laboratory test at selection visit (ASSE). It had been harmonized throughout the protocol to become: “the complete laboratory test at ASSE visit will be performed during the week after selection and preferably between day 5 to 7”. This precision was given in order to obtain the laboratory results around one week after starting the run-in treatment period and to allow a better monitoring of the biological parameters to detect possible modifications induced by the treatment (Perindopril 5 mg / Indapamide 1.25 mg).

This amendement was applicable in all country involved in the study. The purpose of this amendment was to remove the extension period that was added following Amendment No. 3. Indeed, in the countries where the registration was foreseen, the Health Authorities did not require 1 year safety data collection with the highest dose of this combination to reach a Marketing Authorisation. Consequently, the benefit/risk ratio of the study drug being sufficient at the time of the study, the extension part was no more justified. The study title, the study objectives, and the study design were accordingly modified. All patients had to perform the final M4 visit except patients who were already on going in the extension part of the study. For patients already ongoing in the extension period, the study was to be stopped at the next visit planned in the previously approved protocol (M6, M9, M12 or M15). At this final visit, patients were to perform all examinations requested for the withdrawal, including complete laboratory tests, weight and ECG. However, if the consent of the Amendment No. 6 was not obtained, patients were to stop the study at the visit (M6, M9, M12 or M15 visit) and to perform only assessment scheduled at the visit in accordance with the current signed ICF. The other patients who were not yet entered in the extension period were to perform the final visit at M4.