This is a 3 part, phase 1 crossover study in healthy subjects to evaluate the pharmacokinetic profile of KVD824 following single and multiple doses of novel KVD824 modified-release formulations compared with a reference KVD824 immediate release formulation.
Part 1 of the study was a single-centre, open-label, non-randomised, 6-period crossover study designed to investigate the PK and safety of KVD824 MR prototype formulations (with or without an additional KVD824 IR capsule) compared to a reference KVD824 IR capsule formulation in healthy male and female subjects. Part 2 was an optional part designed to investigate the PK and safety of a selected KVD824 MR prototype tablet formulation (with or without an additional KVD824 IR capsule) in healthy male and female subjects in both the fed and fasted state. Note: this Part was not conducted as sufficient information on food effect was collected in the other Parts of the study. Part 3 was a single-centre, randomised, double-blind, placebo-controlled, multiple dose group study to investigate the PK and safety of a selected KVD824 MR prototype tablet formulation (with or without an additional KVD824 IR capsule) in healthy male and female subjects. Part 3 started following completion of Part 1.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
37
300 mg modified-release tablet
300 mg modified-release tablet
300 mg immediate-release capsule
KalVista Investigative Site
Nottingham, United Kingdom
Pharmacokinetics - Tlag
Time prior to the first measurable concentration after single and multiple doses of KVD824
Time frame: Days 1, 10 and 14
Pharmacokinetics - Tmax
Time of maximum observed concentration after single and multiple doses of KVD824 with and without food
Time frame: Days 1, 10 and 14
Pharmacokinetics - Cmax
Maximum observed concentration after single and multiple doses of KVD824 with and without food
Time frame: Days 1, 10 and 14
Pharmacokinetics - Cmax/Dose
Maximum observed concentration divided by dose
Time frame: Days 1, 10 and 14
Pharmacokinetics - C12
Plasma concentration observed at time 12 h after single and multiple doses
Time frame: Days 1, 10 and 14
Pharmacokinetics - C24
Plasma concentration observed at time 24 h after single and multiple doses
Time frame: Days 1, 10 and 14
Pharmacokinetics - Ctrough
Concentration prior to the morning dose on Days 2-14 and prior to the evening dose on Days 2-13
Time frame: Days 2-14
Pharmacokinetics - Cmin
Minimum observed concentration during the dosing interval (between dose time and dose time plus tau) after single and multiple doses of KVD824 with and without food
Time frame: Days 2-14
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Placebo to 300 mg KVD824 Prototype 1 modified-release tablet
300 mg modified-release tablet
Pharmacokinetics - Cavg
Average concentration (AUC(0-tau)/tau)
Time frame: Days 2-14
Pharmacokinetics - AUC(0-12)
Area under the curve from time 0 to 12 hours post-dose after single and multiple doses
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-12)/Dose
Area under the curve from time 0 to 12 hours post-dose divided by dose
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-24)
Area under the curve from time 0 to 24 hours post-dose after single and multiple doses
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-24)/Dose
Area under the curve from time 0 to 24 hours post-dose divided by dose
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-last)
Area under the curve from time 0 to the time of last measurable concentration after single and multiple doses
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-last)/Dose
Area under the curve from time 0 to the time of last measurable concentration divided by dose
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-tau)
Area under the curve for the defined interval between doses (tau)
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-inf)
Area under the curve from time 0 extrapolated to infinity
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUC(0-inf)/D
Area under the curve from time 0 extrapolated to infinity divided by dose
Time frame: Days 1, 10 and 14
Pharmacokinetics - AUCextrap
Area under the curve from time of the last measurable concentration to infinity as a percentage of the area under the curve extrapolated to infinity
Time frame: Days 1, 10 and 14
Pharmacokinetics - T1/2
Terminal elimination half-life after single and multiple doses of KVD824 with and without food
Time frame: Days 1, 10 and 14
Pharmacokinetics - Lambda-z
First order rate constant associated with the terminal (log-linear) portion of the curve after single and multiple doses
Time frame: Days 1, 10 and 14
Pharmacokinetics - CL/F
Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown
Time frame: Days 1, 10 and 14
Pharmacokinetics - CL/Ftau
Total body clearance calculated using AUC(0-tau) after repeated extravascular administration, where F (fraction of dose bioavailable) is unknown
Time frame: Days 1, 10 and 14
Pharmacokinetics - Vz/F
Apparent volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single extravascular administration where F (fraction of dose bioavailable) is unknown
Time frame: Days 1, 10 and 14
Pharmacokinetics - Vz/Flau
Apparent volume of distribution based on the terminal phase calculated using AUC(0-tau) after extravascular administration where F (fraction of dose bioavailable) is unknown
Time frame: Days 1, 10 and 14
Pharmacokinetics - Frel Cmax
Relative bioavailability based on Cmax
Time frame: Days 1, 10 and 14
Pharmacokinetics - Frel AUC(0-12)
Relative bioavailability based on AUC(0-12)
Time frame: Days 1, 10 and 14
Pharmacokinetics - Frel AUC(0-inf)
Relative bioavailability based on AUC(0-inf)
Time frame: Days 1, 10 and 14
Pharmacokinetics - AR Cmax
Accumulation ratio based on Cmax repeated dose/Cmax single dose
Time frame: Days 1, 10 and 14
Pharmacokinetics - Fluctuation
Peak to trough fluctuation (Cmax-Cmin)/Cavg × 100
Time frame: Days 1, 10 and 14
Safety - Adverse Events
Number of Subjects with Adverse Events
Time frame: Change from pre-dose to last visit (up to 14 days)
Safety - Serious Adverse Events
Number of Subjects with Serious Adverse Events
Time frame: Change from pre-dose to last visit (up to 14 days)
Safety - Laboratory Assessments
Number of participants with clinically significant changes in laboratory assessments
Time frame: Throughout the trial to last visit (up to 14 days)
Safety - Vital Signs
Number of participants with clinically significant changes in vital signs
Time frame: Throughout the trial to last visit (up to 14 days)
Safety - ECG
Number of participants with clinically significant changes in electrocardiogram (ECG) measurements
Time frame: Throughout the trial to last visit (up to 14 days)