This study is intended to assess the relative bioavailability between the (extended-release) ER8 capsule formulation (the formulation that is currently used for verinurad development) given under fasted conditions and 2 new capsule formulations of verinurad (A-capsule and B-capsule) given under fed or fasted conditions. All three capsules target an 8-hour release profile (extended-release). The highest dose (12 mg) currently tested in participants will be tested in this study. The study is designed to provide information to optimize the verinurad part of a fixed dose combination capsule to be used in future development.
This study will be a randomised, open-label, single-dose, 5-period, 5-treatment, crossover study in healthy male and female participants, performed at a single study centre. This study is intended to assess the relative bioavailability between the ER8 capsule formulation (the formulation that is currently used for verinurad development) given under fasted conditions and 2 new capsule formulation of verinurad (A-capsule and B-capsule) given under fed or fasted conditions. All three capsules target an 8-hour release profile (extended-release). The highest dose (12 mg) currently tested in participants will be tested in this study. The study is designed to provide information to optimize the verinurad part of a fixed dose combination capsule to be used in future development. The study will comprise: a screening period of maximum 28 days; five treatment periods during which participants will be resident from the morning of the day before dosing with verinurad (Day -1) until at least 72 hours after dosing; discharged on the morning of Day 4 of each Treatment Period; and a follow-up Visit within 7 to 14 days after the last administration of verinurad. There will be a minimum washout period of 5 days between each dose administration. A total of 25 healthy male and female participants will be randomised into this study. Each participant will receive five single-dose treatments of 12 mg verinurad with 240 mL water, following an overnight fast of at least 10 hours. Participants will follow an overnight fast of at least 10 hours before the dosing procedures: for the fed dosing, a high-fat, high-calorie standard breakfast will be served 30 minutes before the planned administration of verinurad to be consumed in full at least 5 minutes before dosing; for the fasted dosing, no breakfast will be served. A meal can be given 4 hours after administration of verinurad for both dosing states. The duration of the study is expected to be approximately 9 weeks for each individual participant (including the 28-day screening period).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Each participant will receive single-dose treatment of 12 mg verinurad ER8 capsule with 240 mL water, following an overnight fast of at least 10 hours.
Each participant will receive single-dose treatment of 12 mg verinurad A-capsule with 240 mL water, following an overnight fast of at least 10 hours.
Each participant will receive single dose treatment of 12 mg verinurad A-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).
Each participant will receive single-dose treatment of 12 mg verinurad B-capsule with 240 mL water, following an overnight fast of at least 10 hours.
Each participant will receive single dose treatment of 12 mg verinurad B-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).
Research Site
Berlin, Germany
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC)
To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
AUC From Time 0 to the Last Quantifiable Concentration (AUC0-t) for the Analysis of PK Parameter
To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Maximum Observed Plasma Concentration (Cmax) for the Analysis of PK Parameter
To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
AUC From Time 0 to 24 Hours Post Dose (AUC0-24) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Pre-dose and up to 24-hours Post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Time of Last Quantifiable Plasma Concentration (Tlast) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Volume of Distribution at Steady State (Intravenous Dosing) (Vss/F) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for the Analysis of PK Parameter
To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time frame: Day 1: Pre-dose and up to 72-hour Post-dose
Number of Participants With Adverse Events (AEs)
To assess AEs as variable of safety and tolerability of single doses of verinurad in healthy participants.
Time frame: From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose)
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