Harmonisation of the slightly different protocol versions which are in force in three participating Countries as consequence of the country specific Amendments implemented in response to Regulatory Authorities (RAs), Ethical Committees (ECs) and Institutional Review Boards. Enlargement of the inclusion to infants who are fed with mixed milk or formula milk, provided that the following specifications on infant’s dietary regimen are met: a) stable and well tolerated dietary regimen b) no change in the dietary regimen until the end of the 7 day treatment period c) cow milk allergy must be excluded d) complementary food not allowed • Deletion of faecal analysis which was intended to be performed as sub-study in Finnish sites, no longer participating to the study. • Update on the Project Responsible Person appointed by the CRO.

Main changes: The age range of eligible patients has been extended by increasing the age upper limit to < 20 weeks at screening visit. The allowed PCA (post-conceptual age) at screening visit has been decreased from >44 to >40 weeks. • Revision of the inclusion criteria specifically pertaining the diagnosis of colic has been made so that a total of 6 hours crying and/or fussing time over a three days screening period is now considered adequate to reflect the Wessel criteria based on a weekly observation time (“paroxysm of irritability, fussing or crying that start and stop without obvious cause for >3h/day, >3 days/week for at least one week”). • Study procedures have been reviewed to avoid unnecessary restriction and therefore to facilitate the inclusion of patients. In particular: - the start of the wash-out period for the exclusion of any pharmacological treatment has been shortened to 24 h before starting the “baby’s day” diary recording at screening (i.e. the day before Day -4) instead of 1 week prior randomisation. As the minimum screening period is 4 days, the wash-out period was at least of 5 days before starting the study treatment. - no change in probiotics and herbal tea intake is required, from 24 h before starting recording the “baby’s day” diary up to completion of post treatment period. • to remove the PK sampling scheduled at visit 3 in order to further reduce any patient discomfort. The “baby’s day” diary has been simplified Administrative changes: number of sites, CRO name,

New sites in Asia and Australia have been included and ClinActis Ltd is the CRO in charge to manage the Asian and Australian sites. The contact details of the CRO have been added to the protocol. • The “Study Responsibility” section has been updated. • Exclusion criterion 5 clarifies that the daily infant’s habits should not be changed during the study conduct, including the use of probiotics, herbal tea and other home remedy. • Paper CRF was replaced by electronic CRF. • Other minor rewording and typos have been included in the protocol review