Clinical Trial: Influence of Naloxone on Ticagrelor Pharmacokinetics and Pharmacodynamics in Patients With Unstable Angina Pectoris on Concomitant Treatment With Morphine

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Differences in the Pharmacokinetic and Pharmacodynamic Profile of Ticagrelor and Its Active Metabolite AR-C124900XX Between Patients With Unstable Angina Pectoris Treated

Brief Summary: The purpose of this study is to evaluate differences in the pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite between patients who received ticagrelor and morphine followed by naloxone versus patients treated with ticagrelor and morphine alone for unstable angina pectoris.

Detailed Summary:

According to contemporary guidelines, ticagrelor is a recommended antiplatelet agent in acute coronary syndromes, including unstable angina pectoris. Quick platelet inhibition plays pivotal role in the treatment of acute coronary syndromes. As evidenced in the IMPRESSION study, analgesia with morphine delays platelet inhibition in patients with acute myocardial infarction. On the other hand, the results of the MOJITO study prove that administration of crushed ticagrelor tablets leads to quicker platelet blockage.

Taking the above into consideration, we created a pharmacokinetic/pharmacodynamic study aiming to evaluate differences between patients who received crushed ticagrelor orally followed by either 1) a combination of intravenous morphine and orally administered naloxone or 2) intravenous morphine alone.

The primary study outcome is time needed for ticagrelor and its active metabolite to reach their maximum plasma concentration in each study arm. Secondary outcomes include ticagrelor and AR-C124900XX maximum concentration and the area under the plasma concentration curve for both agents.

Platelet reactivity will be assessed with the Multiplate Analyzer in all study participants at nine predefined time points.


Sponsor: Collegium Medicum w Bydgoszczy

Current Primary Outcome: Time to maximum concentration (tmax) for ticagrelor and AR-C124900XX for ticagrelor+morphine vs ticagrelor+morphine+naloxone arms [ Time Frame: 6 hours ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Maximum ticagrelor and AR-C124900XX concentration at 6h after administration [ Time Frame: 6 hours ]
  • Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h) [ Time Frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose ]
  • Area under the plasma concentration-time curve for AR-C124900XX (AUC 0-6h) [ Time Frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose ]
  • Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose ]


Original Secondary Outcome: Same as current

Information By: Collegium Medicum w Bydgoszczy

Dates:
Date Received: October 18, 2016
Date Started: October 2016
Date Completion: March 2017
Last Updated: October 19, 2016
Last Verified: October 2016