Pharmacokinetics, Pharmacodynamics, and Safety Study of Ticagrelor in Hemodialysis Patients and Healthy Subjects

NCT02022748 | Completed Phase 1 Results

• 1 other identifier: D5130L00067
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

A phase I, open-label study comparing the pharmacokinetics, pharmacodynamics, safety and tolerability of ticagrelor in hemodialysis patients to healthy subjects with normal renal function.

Conditions

Kidney Failure, Chronic

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic Parameter Cmax of Ticagrelor

  0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dose

• Pharmacokinetic Parameter Cmax of AR-C124910XX

  0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dose

• Pharmacokinetic Parameter AUC0-∞ (Area Under the Plasma Concentration-time Curve From Time Zero to Infinity) of Ticagrelor

  0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dose

• Pharmacokinetic Parameter AUC0-∞ of AR-C124910XX

  0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dose

Secondary Outcomes (2)

• Pharmacokinetic Parameter t1/2 of Ticagrelor

  3 days

• Pharmacokinetic Parameter t1/2 of AR-C124910XX

  3 days

Study Arms (3)

Sequence 1

EXPERIMENTAL

hemodialysis patients: subjects will receive treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 1 and treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 2.

Drug: ticagrelor

Sequence 2

EXPERIMENTAL

hemodialysis patients: subjects will receive treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 1 and treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 2.

Drug: ticagrelor

Treatment H

EXPERIMENTAL

Healthy subjects: ticagrelor oral 90 mg on 1 day of treatment

Drug: ticagrelor

Interventions

ticagrelor DRUG

Group A is hemodialysis subjects. Crossover design will be implemented for Group A subjects. Group A will be randomized into 2 sequences, Sequence 1 and Sequence 2. In Sequence 1, subjects will receive treatment A in Period 1 and treatment B in Period 2. Washout period of at least 7 days between Period 1 and Period 2 in Sequence 1. Treatment A and Treatment B are defined as follows: Treatment A subjects will be dosed with oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session. Treatment B will be dosed with oral 90 mg ticagrelor tablet just prior to dialysis session.

Also known as: Brilinta

Sequence 1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female aged 18 to 80 years (inclusive).
• Normal renal function (CrCl of ≥90 mL/min) or End Stage Renal Disease (ESRD) requiring hemodialysis.

You may not qualify if:

• Any indication for oral anticoagulant or anti platelet treatment during study period. Must be off treatment for at least 3 weeks (low dose 81mg aspirin is allowed for hemodialysis subjects only).
• Acute Coronary Syndrome (ACS) within past 12 months.
• Contraindications to ticagrelor (ie: active pathological bleeding, severe hepatic impairment, history of hemorrhagic stroke, allergic to ticagrelor).
• Platelet count \<100000/μL, hemoglobin \<9g/dL
• Blood donation within 90 days of dosing
• Risk for bradycardia
• Investigational drug within 30 days or 6 half-lives, whichever is longer, before dosing
• Concomitant therapy with CYP3A inhibitors/substrates with narrow therapeutic index,or strong CYP3A inducers 14 days before dosing until completion of the follow-up visit.
• History of alcohol, drug, or substance abuse within the past year
• Clinically significant laboratory abnormalities as judged by the investigator.
• Increased bleeding risk including GI bleeding in past 30 days; history of intracranial, retroperitoneal, or spinal bleeding, recent major trauma within 30 days of dosing, Sustained uncontrolled hypertension, history of hemorrhagic disorders.
• Pregnant or lactating females, or females of child-bearing potential (ie, those who are not chemically or surgically sterilised or who are not post-menopause) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator throughout the duration of the study OR females who have a positive pregnancy test at Visit 1.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Lakewood, Colorado, 80228, United States

Location

Research Site

Minneapolis, Minnesota, 55404, United States

Location

Related Publications (1)

• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

  PMID: 35224730 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Naeem Khan, MD
• Organization: AstraZeneca Pharmaceuticals LP

Naeem.Khan@astrazeneca.com

+1 302-885-8976

Study Officials

• Jolene K Berg, MD

  DaVita Clinical Research, Minneapolis, MN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2013
• First Posted: December 30, 2013
• Study Start: December 29, 2013
• Primary Completion: May 9, 2016
• Study Completion: May 9, 2016
• Last Updated: January 17, 2018
• Results First Posted: September 29, 2017

Record last verified: 2018-01

Locations

US (2)