Study to Assess Effect of Cyclosporine on the Blood Levels of Ticagrelor

A Single-Center,Open-Label,Randomized,3-Treatment,3-Period Cross-Over Study to Investigate the Potential Effect of Cyclosporine on the Pharmacokinetics, Safety, and Tolerability of Ticagrelor and the Effect of Ticagrelor on the Pharmacokinetics, Safety, and Tolerability of Cyclosporine

The purpose of this study is to assess the effect of Cyclosporine on the blood levels of Ticagrelor.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: cyclosporine; Drug: ticagrelor

Detailed Description

A Single-Center,Open-Label,Randomized,3-Treatment,3-Period Cross-Over Study to Investigate the Potential Effect of Cyclosporine on the Pharmacokinetics, Safety, and Tolerability of Ticagrelor and the Effect of Ticagrelor on the Pharmacokinetics, Safety, and Tolerability of Cyclosporine.

• Study Type: Interventional
• Enrollment (Actual): 20
• 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 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Provision of signed and dated written informed consent prior to any study-specific procedures
• Healthy male subjects aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venipuncture

Exclusion Criteria:

• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• A history of hemophilia, von Willebrand's disease, lupus anti-coagulant, 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 hemorrhage, hematemesis, melena, hemoptysis, severe epistaxis, severe thrombocytopenia, intracranial hemorrhage, or rectal bleeding within 1 year

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; cyclosporine 600 mg+ a single oral dose of 180 mg ticagrelor	Drug: cyclosporine; Oral tablets, 600 mg , single dose; Drug: ticagrelor; Oral tablets, 180 mg, single dose
Experimental: B; single dose cyclosporine 600 mg	Drug: cyclosporine; Oral tablets, 600 mg , single dose
Experimental: C; single dose 180 mg ticagrelor	Drug: ticagrelor; Oral tablets, 180 mg, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the pharmacokinetic (PK) profile for Ticagrelor and its metabolite AR-C124910XX in terms of maximum concentration (Cmax),time to maximum concentration (tmax) and area under the concentration curve from time zero to infinity (AUC)	PK samples will be collected postdose at visits 2,3 and 4	PK samples will be collected postdose 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours
Description of the PK profile for Ticagrelor and its metabolite AR-C124910XX in terms of area under the concentration-time curve from time zero to the last measurable concentration (AUC(0-t)),terminal half-life (t1/2)	PK samples will be collected postdose at visit 2,3 and 4	PK samples will be collected postdose 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours
Description of the PK profile for AR-C124910XX : ticagrelor in terms of ratios for Cmax, AUC(0-t), and AUC	PK samples will be collected postdose at visit 2,3 and 4	PK samples will be collected postdose 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours
Description of the PK profile for Cyclosporine in terms of Cmax, AUC(0-t), AUC, tmax and t1/2	PK samples will be collected postdose at visit 2,3 and 4	PK samples will be collected postdose 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Description of the safety profile in terms of adverse events, blood pressure, pulse, temperature, ECG (Electrocardiogram), physical examination, and safety laboratory variables	Baseline up to 45 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Chair: Miriana Kujacic, MD, Molndal, Sweden AstraZeneca; Principal Investigator: Kelli Craven, MD, Overland Park US, Quintiles, Inc.

Publications and helpful links

General Publications

• Teng R, Kujacic M, Hsia J. Pharmacokinetic interaction study of ticagrelor and cyclosporine in healthy volunteers. Clin Drug Investig. 2014 Aug;34(8):529-36. doi: 10.1007/s40261-014-0205-2.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: January 2, 2012
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (Estimate): January 6, 2012

Study Record Updates

• Last Update Posted (Estimate): December 12, 2012
• Last Update Submitted That Met QC Criteria: December 11, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; Phase 1; Healthy male volunteers; ticagrelor; cyclosporine; Bioavailability (plasma AUC, Cmax, plasma AUC0-t, t1/2λz, tmax)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Ticagrelor; Cyclosporine; Cyclosporins
• Other Study ID Numbers: D5130C00074