Pharmacokinetics, Pharmacodynamics, and Safety Study of Ticagrelor in Hemodialysis Patients and Healthy Subjects
Condition: Kidney Failure, Chronic
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Intervention: ticagrelor; ticagrelor; ticagrelor
Intervention description: 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.; 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 2, subjects will receive treatment B in Period 1 and treatment A in Period 2. Washout period of at least 7 days between Period 1 and Period 2 in Sequence 2. 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.; Group B is healthy subjects. Group B healthy subjects will receive oral 90 mg ticagrelor referred to as Treatment H.
Intervention MeSH terms: Ticagrelor
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.