Study to Investigate if the Uptake of Ticagrelor Into the Body Differs Depending on Method of Administration.

An Open-label, Randomised, 3-period, 3-treatment, Crossover, Single-centre, Single-dose, Bioavailability Study With Alternative Methods of Administration of Crushed Ticagrelor Tablets, 90 mg, Compared to Whole Ticagrelor Tablets, 90 mg, in Healthy Volunteer

Study to investigate if the uptake of Ticagrelor into the body differs depending on method of administration.

Study Overview

• Status: Completed
• Conditions: Bioavailability Heathy Volunteers
• Intervention / Treatment: Drug: Ticagrelor 90 mg whole tablet; Drug: Ticagrelor 90 mg tablet crushed; Drug: Dispersed ticagrelor 90 mg tablet suspended in water - nasogastric tube

Detailed Description

Study to evaluate the bioavailability of the crushed ticagrelor tablets when administered orally or through nasogastric tubes compared to whole ticagrelor tablets given orally

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • 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:

• Healthy male and female volunteers aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venepuncture
• Have a body mass index between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg (110 pounds [lbs]) and no more than 100 kg (220 lbs).
• Provision of signed and dated, written informed consent prior to any study specific procedures

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
• History of haemophilia, von Willebrand's disease, lupus anticoagulant or other diseases/syndromes that can either alter or increase the propensity for bleeding
• A personal history of vascular abnormalities including aneurysms; a personal history of severe haemorrhage, haematemesis, melena, haemoptysis, severe epistaxis, severe thrombocytopenia, intracranial haemorrhage; or rectal bleeding within 3 months prior to the screeening visit; or history suggestive of peptic ulcer disease
• History of frequent and/or significant nose bleed or clinically significant non traumatic bleed, bruise/haematoma or any other clinically significant bleeding risk, as judged by the Investigator

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Ticagrelor 90 mg as a whole tablet	Drug: Ticagrelor 90 mg whole tablet; Ticagrelor 90 mg whole tablet administered as a single oral dose
Experimental: B; Ticagrelor 90 mg tablet crushed and suspended in water	Drug: Ticagrelor 90 mg tablet crushed; Ticagrelor 90 mg crushed and suspended in water
Experimental: C; Dispersed ticagrelor 90 mg tablet suspended in water and administered through a nasogastric tube into the the stomach	Drug: Dispersed ticagrelor 90 mg tablet suspended in water - nasogastric tube; Dispersed 90 mg ticagrelor 90 mg tablet suspended in water and administered through a nasogastric tube into the stomach

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Description of the pharmacokinetic(PK) profile in terms of plasma concentration-time curve (AUC) of ticagrelor	PK samples will be collected pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
Description of the pharmacokinetic(PK) profile in terms of AUC of the active metabolite of ticagrelor	PK samples will be collected pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
Description of the pharmacokinetic(PK) profile in terms of maximum plasma concentration (Cmax) of ticagrelor	PK samples will be collected pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
Description of the pharmacokinetic(PK) profile in terms of Cmax of the active metabolite of ticagrelor	PK samples will be collected pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Description of the safety profile in terms of adverse events (AE)	From first dose through to the follow-up visit.
Description of the safety profile in terms of laboratory variables	Safety labs at screening, Day -1, Day 3 (48 hours after treatment) and follow-up
Description of the safety profile in terms of vital signs	Vital signs at screening, pre-dose, 1 h, 3, 6, 12 and 24 hours post-dose, Day 3 for all treatment periods and follow-up
Description of the safety profile in terms of physical examination findings	Physical examination at screening, pre-dose, Day 3 and follow-up
Description of the safety profile in terms of Electrocardiogram (ECG)	ECGs at screening, Day 3 and follow-up

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Judith Hsia, MD, Astrazeneca, Wilmington, US; Study Chair: Mirjana Kujacic, MD, AstraZeneca Mölndal, Sweden; Principal Investigator: Saeed Kahn, MBBS, Quintiles London, United Kingdom

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: June 25, 2013
• First Posted (Estimate): June 27, 2013

Study Record Updates

• Last Update Posted (Estimate): September 18, 2013
• Last Update Submitted That Met QC Criteria: September 17, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Phase 1, pharmacokinetic, safety, Ticagrelor
• 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
• Other Study ID Numbers: D5130C00076