Study to See if Platelet Transfusion Stop or Lessen the Effect of the Drug on Platelets

A Open Label, Randomized, Crossover and Potential Parallel, Single Dose Study of Ticagrelor 180 mg and Acetylsalicylic Acid (ASA) in Healthy Volunteers Followed by Autologous in Vivo Platelet Transfusion to Determine the Effects of Platelet Supplementation on the Reversibility of Platelet Inhibition

Study to see if platelet transfusion stop or lessen the effect of the drug on platelets

Study Overview

• Status: Completed
• Conditions: Inhibition on Platelet Aggregation
• Intervention / Treatment: Drug: Ticagrelor; Drug: ASA; Drug: Clopidogrel

Detailed Description

A open label, randomized, crossover and potential parallel, single dose study of ticagrelor 180 mg and acetylsalicylic acid (ASA) in healthy volunteers followed by autologous in vivo platelet transfusion to determine the effects of platelet supplementation on the reversibility of platelet inhibition

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures
• Healthy male and/or female volunteers aged 18 to 50 years, inclusive, with suitable veins for cannulation or repeated venipuncture. (Healthy as determined by medical history and physical examination, laboratory parameters, electrocardiogram (ECG) perform
• Have a body mass index (BMI) between 18 and 35 kg/m2 (inclusive) and weigh at least 50 kg and no more than 120 kg

Exclusion Criteria:

• ADP induced platelet aggregation <60% prior to platelet apheresis
• History of peptic ulcer disease Healthy volunteers with a propensity to bleed (eg, due to recent trauma, recent surgery, active or recent gastrointestinal bleeding or moderate hepatic impairment)
• Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the investigational product
• Current smokers, those who have smoked or used nicotine products within the previous 3 months and those who tested positive for cotinine at screening or at admission to the study center

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Ticagrelor with Platelet transfusion	Drug: Ticagrelor; Oral single loading dose 180ng; Drug: ASA; 81mg once daily from day -2 up to platelet transfusion
Experimental: 2; Ticagrelor without Platelet transfusion	Drug: Ticagrelor; Oral single loading dose 180ng; Drug: ASA; 81mg once daily from day -2 up to platelet transfusion
Active Comparator: 3; Clopidogrel with Platelet transfusion	Drug: ASA; 81mg once daily from day -2 up to platelet transfusion; Drug: Clopidogrel; Oral single loading dose 600mg
Active Comparator: 4; Clopidogrel without Platelet transfusion	Drug: ASA; 81mg once daily from day -2 up to platelet transfusion; Drug: Clopidogrel; Oral single loading dose 600mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics in terms of percent of inhibition of adenosine phosphatase (ADP)-induced platelet aggregation assessed by light transmission aggregometry (LTA) after loading dose of Ticagrelor	Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics in terms of platelet reactivity as measured by P2Y12 Reaction Units (PRU) using VerifyNow™ after loading dose of Ticagrelor	Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h
Pharmacodynamics in terms of platelet reactivity as measured by P2Y12 Reaction Units (PRU) using VerifyNow™ after loading dose of Clopidogrel	Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h
Pharmacodynamics in terms of percent of inhibition of adenosine phosphatase (ADP)-induced platelet aggregation assessed by light transmission aggregometry (LTA) after loading dose of Clopidogrel	Predose, 0h, 2h,6h,12h,24h,36h,48h,60h,72h,84h and 96h
Safety profile in terms of adverse events, blood pressure, pulse, temperature, ECG (Electrocardiogram), physical examination, and safety laboratory variables	up to 9 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Chair: Glenn Carlson, MD, AstraZeneca Wilmington US; Principal Investigator: Phil Leese, MD, Overland Park US, Quintiles, Inc; Study Director: Judi Hsia, MD, Wilmington, US AstraZeneca

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: December 5, 2012
• First Submitted That Met QC Criteria: December 5, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Estimate): April 24, 2014
• Last Update Submitted That Met QC Criteria: April 23, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Platelets; Phase 1 Safety ,; pharmacodynamic,; Ticagrelor,; Clopidogrel,
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: D5130C00079