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

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ClinicalTrials.gov Identifier: NCT02939248
Recruitment Status : Completed
First Posted : October 19, 2016
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
Jacek Kubica, Collegium Medicum w Bydgoszczy

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.

Condition or disease Intervention/treatment Phase
Unstable Angina Pectoris Drug: Crushed ticagrelor followed by morphine Drug: Crushed ticagrelor, morphine,naloxone Phase 4

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2016
Actual Primary Completion Date : December 2018
Actual Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angina

Arm Intervention/treatment
Active Comparator: Crushed ticagrelor followed by morphine
crushed ticagrelor 180 mg administered orally followed by morphine 5 mg intravenously
Drug: Crushed ticagrelor followed by morphine
Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously
Other Name: Brilique

Active Comparator: Crushed ticagrelor, morphine,naloxone
crushed ticagrelor 180 mg administered orally followed by morphine 5 mg intravenously and naloxone 1 mg orally
Drug: Crushed ticagrelor, morphine,naloxone
Crushed ticagrelor (180 mg) orally followed by morphine 5 mg intravenously and naloxone 1 mg orally
Other Name: Brilique




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

Secondary Outcome Measures :
  1. Maximum ticagrelor and AR-C124900XX concentration at 6h after administration [ Time Frame: 6 hours ]
  2. 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 ]
  3. 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 ]
  4. 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 ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02939248


Locations
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Poland
Cardiology Department, Dr. A. Jurasz University Hospital
Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-094
Sponsors and Collaborators
Collegium Medicum w Bydgoszczy
Investigators
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Principal Investigator: Jacek Kubica, MD., PhD. Cardiology Department, Dr. A. Jurasz University Hospital

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Responsible Party: Jacek Kubica, Prof. Jacek Kubica, MD, PhD, Collegium Medicum w Bydgoszczy
ClinicalTrials.gov Identifier: NCT02939248     History of Changes
Other Study ID Numbers: CMUMK202G
First Posted: October 19, 2016    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Additional relevant MeSH terms:
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Angina Pectoris
Angina, Unstable
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Morphine
Naloxone
Ticagrelor
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Narcotic Antagonists