Pharmacokinetics, safety, and efficacy of tapentadol oral solution for treating moderate to severe pain in pediatric patients

Abstract

Background: This trial is part of the global pediatric clinical development program investigating the administration of the strong analgesic tapentadol in children and adolescents. Patients and methods: The single site, open-label phase 2 trial evaluated the pharmacokinetic profile of tapentadol and its major metabolite, tapentadol-O-glucuronide, as well as safety and tolerability and efficacy of a single dose of tapentadol oral solution (1 mg/kg) in patients (2 to <18 years) undergoing dental, ear, nose, or throat surgery. Blood sampling and pain intensity measurements were conducted using age-appropriate schedules and rating scales, respectively. Adverse events were monitored throughout the trial. Results: Sixty-six patients were treated. They were stratified by age: Group 1 (12 to <18 years), n=21; Group 2 (6 to <12 years), n=28; and Groups 3 (3 to <6 years) and 4 (2 to <3 years), n=17. Serum tapentadol concentrations observed in these pediatric patients were within the range observed in adults after administration of a single tapentadol immediate-release dose (50-100 mg), whereas those of the metabolite tapentadol-O-glucuronide were within the same range or lower than in adults who received comparable single doses of tapentadol. Pain intensity improved over time across all age groups. The most common treatment-emergent adverse events were nausea (24.2%), vomiting (16.7%), dizziness (9.1%), and headache (6.1%). Conclusion: A single dose of tapentadol oral solution (1 mg/kg) administered to pediatric patients (2 to <18 years) resulted in serum tapentadol concentrations within the targeted range shown to be safe and efficacious in adults. Tapentadol demonstrated good tolerability and safety; within the limitations of the trial design, improvements in postsurgical pain intensity were observed across the age groups. Tapentadol may provide a new treatment option in the management of moderate to severe pediatric pain.

Keywords: analgesics; moderate to severe pain; opioid receptors; pediatric pain management; tapentadol.

Conflict of interest statement

E. Tarau is an employee of Grünenthal USA Inc., C. Lefeber, M. Sohns, and J. Goldberg are employees of Grünenthal GmbH. M. Brett and R. Rosenburg were employees of Grünenthal GmbH at the time the trial was conducted. R Rosenburg was the international clinical lead for the pediatric project at Grünenthal until Sep 2017. The authors report no other conflicts of interest in this work.

Figures

Figure 1

Patient flow chart. Notes: Group 1, 12 to <18 years, group 2, 6 to <12 years, group 3, 3 to <6 years, and group 4, 2 to <3 years. Abbreviations: AE, adverse event; PK, pharmacokinetic.

Figure 2

Mean serum tapentadol concentration in adolescents in Group 1 (12 to Note: Adult data have been dose-corrected to a single dose of tapentadol 80 mg, which approximates the dose of 1 mg/kg used in the current pediatric trial.

Figure 3

Individual serum concentrations of tapentadol in pediatric patients (2 to

Figure 4

Mean pain intensity over time using the (A) visual analog scale, (B) color analog scale, (C) faces pain scale-revised, and (D) face, legs, activity, cry, and consolability assessments. Abbreviations: VAS, visual analog scale; CAS, color analog scale; FPS-R, faces pain scale-revised; FLACC, face, legs, activity, cry, and consolability score.

Figure 5

Kaplan-Meier curves for time to first intake of supplemental analgesic medication by age group. Note: Censored patients are patients who did not take any supplemental analgesics until the discharge visit (censoring was at the time point of the discharge visit).