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

Unstable Angina Pectoris Clinical Trial

Official title:

Differences in the Pharmacokinetic and Pharmacodynamic Profile of Ticagrelor and Its Active Metabolite AR-C124900XX Between Patients With Unstable Angina Pectoris Treated With Crushed Ticagrelor and a Combination of Morphine and Naloxone or Morphine Alone - a Randomized Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02939248
• Other study ID #: CMUMK202G
• Status: Completed
• Phase: Phase 4
• Start date: October 2016
• Est. completion date: December 2018

Study information

• Verified date: March 2019
• Source: Collegium Medicum w Bydgoszczy
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures

• Diagnosis of unstable angina

• Male or non-pregnant female, aged 18-80 years

• Provision of informed consent for angiography and PCI

• GRACE score <140 pts

Exclusion Criteria:

• treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment

• current treatment with morphine or any opioid "mi" receptor agonist

• hypersensitivity to ticagrelor

• current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin

• active bleeding

• history of intracranial hemorrhage

• recent gastrointestinal bleeding (within 30 days)

• history of coagulation disorders

• platelet count less than <100 x10^3/mcl

• hemoglobin concentration less than 10.0 g/dl

• history of moderate or severe hepatic impairment

• history of major surgery or severe trauma (within 3 months)

• risk of bradycardic events as judged by the investigator

• second or third degree atrioventricular block during screening for eligibility

• history of asthma or severe chronic obstructive pulmonary disease

• kidney disease requiring dialysis

• manifest infection or inflammatory state

• Killip class III or IV during screening for eligibility

• respiratory failure

• history of severe chronic heart failure (NYHA class III or IV)

• concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment

• body weight below 50 kg

Related Conditions & MeSH terms

• Angina Pectoris
• Angina, Unstable
• Unstable Angina Pectoris

Intervention

Drug:
• Crushed ticagrelor followed by morphine
Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously
• Crushed ticagrelor, morphine,naloxone
Crushed ticagrelor (180 mg) orally followed by morphine 5 mg intravenously and naloxone 1 mg orally

Locations

Country	Name	City	State
Poland	Cardiology Department, Dr. A. Jurasz University Hospital	Bydgoszcz	Kujawsko-Pomorskie

Sponsors (1)

Lead Sponsor	Collaborator
Collegium Medicum w Bydgoszczy

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to maximum concentration (tmax) for ticagrelor and AR-C124900XX for ticagrelor+morphine vs ticagrelor+morphine+naloxone arms		6 hours
Secondary	Maximum ticagrelor and AR-C124900XX concentration at 6h after administration		6 hours
Secondary	Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h)		prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
Secondary	Area under the plasma concentration-time curve for AR-C124900XX (AUC 0-6h)		prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
Secondary	Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry		prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose