Conditions: Kidney Failure, Chronic
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 27
Healthy volunteers: yes

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.

Detailed description:
This will be a single dose, randomised, open label, parallel group study conducted in the US to examine the Pharmacokinetics (PK), Pharmacodynamics (PD), safety, and tolerability of ticagrelor in end stage renal disease (ESRD) subjects on hemodialysis (HD) compared with healthy subjects with normal renal function. Up to a total of 30 male and female adult subjects aged 18 to 80 years (inclusive) with a weight of at least 50 kg and a body mass index between 18 and 40 kg/m2 (inclusive), will be dosed to assure that there will be 20 evaluable subjects (10 subjects on HD and in 10 healthy subjects with normal renal function (CrCL ≥90 mL/min). The normal renal function groups should have a similar distribution with respect to age, weight and gender. Subjects will be required to have an inpatient stay from the day prior to dosing until the 48-hour post-dose time-point to ensure that all PK samples are collected at the appropriate timepoints. The study will be conducted in two groups: Group A consisting of ESRD subjects on HD, Group B consisting of healthy subjects. A crossover design will be implemented for Group A subjects as follows: Group A subjects will be randomized into two sequences, Sequence 1 and Sequence 2. In Sequence 1, subjects will receive treatment A in Period 1 and treatment B in Period 2. There will be washout period of at least 7 days between Period 1 and Period 2 in Sequence 1. Similarly in Sequence 2, subjects will receive treatment B in Period 1 and treatment A in Period 2. There will be a washout period of at least 7 days between Period 1 and Period 2 in Sequence 2 as well. Treatment A and treatment B are defined as follows: Treatment A: subjects will be dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session; • Treatment B: subjects will be dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.(NB: Treatment B dosing should occur within 5 minutes of dialysis start). Group B subjects (healthy subjects) with normal renal function (CrCL of ≥ 90 mL/min) will receive just an oral 90 mg ticagrelor referred to as treatment H. All doses will be administered in an open-label design.

Arms:
arm 1: 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. arm 2: 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. arm 3: Healthy subjects: ticagrelor oral 90 mg on 1 day of treatment

Interventions: intervention 1: ticagrelor intervention 2: ticagrelor intervention 3: ticagrelor
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: Group B is healthy subjects. Group B healthy subjects will receive oral 90 mg ticagrelor referred to as Treatment H.

Protocol document: