Development Strategy and Relative Bioavailability of a Pediatric Tablet Formulation of Ticagrelor

Clin Drug Investig. 2019 Aug;39(8):765-773. doi: 10.1007/s40261-019-00800-w.

Abstract

Background and objective: Ticagrelor is a P2Y12 receptor inhibitor approved as an antiplatelet drug for patients with acute coronary syndrome or a history of myocardial infarction. Ticagrelor is also being investigated for the reduction of vaso-occlusive crises in pediatric patients with sickle cell disease. A pediatric formulation suitable for this age range was developed; the development strategy is described. Primary objectives were determining the relative bioavailability of ticagrelor pediatric tablets and granules for oral suspension to the adult immediate-release tablet, and the pediatric tablets taken whole and dispersed/suspended in water to the granules for oral suspension. Bioequivalence between the pediatric tablet taken whole or suspended in water was also assessed. Secondary objectives were comparing the formulations' safety and tolerability.

Methods: We conducted a randomized, four-period, cross-over, single-dose study. Pharmacokinetic parameters were assessed for ticagrelor and its active metabolite AR-C124910XX. Bioequivalence was concluded if the 90% confidence intervals of the maximum plasma concentration and area under the plasma concentration-time curve ratios were contained completely within the 80.00-125.00% limits for ticagrelor/AR-C124910XX.

Results: Forty-four healthy adults (95% white; 57% male) were included. Similar bioavailability of ticagrelor (and AR-C124910XX) was demonstrated for all comparisons tested. Ticagrelor pediatric tablets taken whole were bioequivalent to pediatric tablets suspended in water. The plasma concentration-time profiles for ticagrelor and AR-C124910XX were similar, showing rapid ticagrelor absorption and AR-C124910XX formation. All formulations were well tolerated.

Conclusion: Similar bioavailability of a new pediatric dispersible tablet formulation of ticagrelor for use across a wide age range of pediatric patients was demonstrated compared with other oral ticagrelor formulations. CLINICALTRIALS.

Gov identifier: NCT03126695.

Eudract: 2017-000371-93.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenosine / analogs & derivatives
  • Adolescent
  • Biological Availability
  • Child
  • Cross-Over Studies
  • Female
  • Humans
  • Male
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / pharmacokinetics*
  • Tablets*
  • Therapeutic Equivalency
  • Ticagrelor / administration & dosage
  • Ticagrelor / pharmacokinetics*

Substances

  • AR C124910XX
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Tablets
  • Ticagrelor
  • Adenosine

Associated data

  • ClinicalTrials.gov/NCT03126695