Participants were given approximately 25 milliliter (mL) of water after dosing to help ensure all medication was cleared from the mouth and swallowed and the obligatory intake of 100 mL to 150 mL of water at 1 hour after dosing was removed.

The description of safety was moved to precede the efficacy section since PK analyses and safety were 2 primary objectives of the study; Type and use of concomitant rescue analgesic medications were made clear to prevent intolerable pain to participants; Study stopping and participant withdrawal (discontinuation) criteria were modified for tapentadol administration, any potential safety findings, and regulatory requirements to ensure that caution was used to enroll participants; Methods for statistical analyses for safety and pain intensity were revised to include analyses based on concurrent use of analgesic medications; All participants who received study medication but were excluded from the PK analysis were to be included in the safety analysis; Study design was revised to include more details about participant screening, tapentadol administration, and the maximum single oral dose; Additions and modifications were made to inclusion and exclusion criteria to improve the safety for the pediatric population; Safety evaluations were revised to add baseline criteria assessments and type and timing of clinical laboratory tests, 12-lead ECG, and end-of-study physical examination.

The main reason for this amendment was to improve enrollment in the study while preserving the original intent and objectives of the study. This amendment was considered to be substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European Union.

Modifications were made to the study design and the inclusion and exclusion criteria to facilitate study enrollment while preserving original intent and objectives of the study; The study design was modified to enroll participants pre- or post-operatively; The inclusion criteria were modified to include participants with: dental surgeries or postoperative pain that requires opioid treatment as per the investigator’s clinical judgment; Ibuprofen (4-10 mg/kg every 6-8 hours) or naproxen (2.5-10 mg/kg every 8-12 hours) was allowed as supplemental analgesic medication; Participants with contraindications to ibuprofen or naproxen, or significant infectious disease were to be excluded from the study; The safety evaluations were modified to include that physical examination and 12-lead ECG will be performed at screening.

The primary objective of this amendment was to permit the enrollment of subjects who were ≥ 6 years of age. This was based on a recommendation from a recent Advisory Committee for Pharmaceutical Science and Clinical Pharmacology (IDRAC 137880 [ACPSCP]), which took place in March 2012. A majority (12 or 13) of the Committee members agreed that the dose of a drug for adolescents may be derived using adult data without the need for a dedicated pharmacokinetic study. Furthermore, the extensive clinical and pharmacological experience with tapentadol supports the use of modeling to select a dose for testing in subjects who are ≥ 6 years of age. This amendment also allowed for the use of any nonsteroidal anti-inflammatory drug (NSAID) for supplemental analgesic medication in the event of persistent pain, instead of limiting the permitted NSAIDs to just ibuprofen and naproxen. This amendment was considered to be substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European Union.