Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial

Abstract

Cardiovascular diseases are the leading cause of death worldwide. Ticagrelor is an oral antiplatelet drug used in acute coronary syndrome. Although generic drugs are approved for their bioequivalence to the original product, they are not necessarily to be therapeutically equivalent. This study was conducted to prove the efficacy and safety of ticagrelor generically named Ticaloguard® compared to its brand Brilique® in healthy volunteers. A loading dose of 180 mg ticagrelor named Brilique® or Ticaloguard® followed by a 90 mg twice daily regimen as maintenance dose was given to 14 and 15 volunteers in Tica and Brili groups, respectively. The platelet aggregation on the ADP agonist was assessed at baseline and repeated 1 h and 3 h after the loading dose, on day 4 (after reaching steady-state), 12 and 24 h after discontinuation of the antiplatelet drug. Adverse effects from trial medications were noted by direct questions. It was shown that generic Ticaloguard® provides a similar therapeutic effect and safety as its branded Brilique® (p > 0.05). This will permit safe and trusted use of the generic Ticaloguard® when treating it in the same manner as Brilique®. Testing generic drug effects rather than simple bioequivalency, especially for drugs that are used in critical life-threatening situations, is crucial. We advocate applying this form of a clinical trial to test surrogate clinical efficacy for generics used in critical indications before having real-world data whenever possible.

Keywords: Acute coronary syndrome; Ticagrelor. Generics.

Fig. 1

Volunteer flow chart. Abbreviation: Brili, Brilique®; Tica, Ticaloguard®

Fig. 2

(a) Effect of generic Ticaloguard® and brand Brilique® on ADP aggregation and (b) platelet inhibition at different time intervals. Abbreviations: LD, loading dose; Css, steady-state concentration