The amendment was implemented after completion of Part 1 of the study, but before study drug administration began in Part 2 of the study. The important changes in the amendment included the following: participants need to be admitted to NICU or step-down unit prior to alimentation by a feeding tube (6 F NG or OG); Clarification on minimum number of subjects needed in Part 2 of study and undergoing pHmetry; Clarification on changes made to reflect the selection of 2 dose levels and formulation for Part 2. Dosing instructions for Part 2 were updated; Clarification on certain assessments done in subjects undergoing or not undergoing pHmetry in the Part 2 of study; Additional exclusion criteria for continuous feeding, and mothers taking PPIs and breast feeding; In Part 1 of the study, for serum laboratory assessment, the safety laboratory parameters were changed to: Hemoglobin, hematocrit, sodium, potassium, chloride, calcium, bicarbonate, AST, ALT, total bilirubin, direct bilirubin, albumin, BUN, glucose, creatinine, and total protein; Clarification on certain medications allowed or disallowed during the study; Capillary sampling for PK was allowed; but venous collection was preferable; Blood volume for PK evaluation was reduced to 0.4 mL per sample; Indication that the PK samples collected between 2- to 3-hours postdose and 3- to 4-hours postdose should be separated by at least 1 hour.

The amendment was implemented in Part 2 of the study before study drug administration which began for 21 participants. The important changes in amendment included the following: Instead of 6 F NG or OG feeding tube only, a ≥6 F NG or OG feeding tube may be used; 6.5 F silicone NG or OG tubes should be avoided. Due to dosing issues with vehicle tablet (described below), vehicle granules supplied in sachets instead of vehicle tablets were used for dosing in Part 2 -directions for dose preparation were updated The reason for this amendment was the occurrence of clogging of NG or OG tube in 5 participants (participants 1175001, 1085003, 1105002, 1085004 and 1455001) who had been randomized to the 3 mg dose group of rabeprazole. In one participants (participants 1105002), the occurrence of tube clogging was reported as a study-drug related TEAE. This dose (3 mg) of study drug required 2 vehicle tablets to be added to water in order to form suspension with the rabeprazole granules. Participants randomized to the 2 mg dose only required one vehicle tablet to form the suspension and did not experience NG or OG tube clogging. After reports of difficulty with infusion of the study drug during the first administration in some participants receiving the 3 mg dose, several mitigation strategies were employed including avoidance of 6.5 F silicone NG or OG tubes (more adherence of suspension in silicone tubes vs. tubes made of other materials); vigorous shaking of the suspension in syringe just prior to infusion via NG or OG tube; Use of an interval water flush midway through the infusion of the suspension; and changing to an 8 F feeding tube in infants with a 6 F tube in place. With these mitigation strategies, full timely doses of study drug were able to be administered to participants. Protocol Amendment INT-2 substituted the vehicle granules as suspending agent instead of the vehicle tablet.

The amendment was implemented in Part 2 of the study before study drug administration began for 18 participants. This included a further clarification on the feeding regimens for participants undergoing pHmetry and not undergoing pHmetry.