This is a 3 part phase 1, randomized, double-blind, placebo-controlled, study of the safety, tolerability, and pharmacokinetics of KVD824 following administration of single and multiple ascending oral doses; followed by a crossover food effect sub-study in healthy male volunteers.
Part A was a single-centre randomized, double blinded, placebo control to investigate the safety and tolerability of single ascending doses of KVD824 administered to healthy male volunteers. Part B was a single centre, randomized, double blinded, placebo control to investigate the safety and tolerability of multiple ascending doses of KVD824 administered to healthy male volunteers. Part C was a single-centre, open labelled to investigate the food effect.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
108
Active
Placebo
KalVista Investigative Site
Merthyr Tydfil, United Kingdom
Safety - Treatment Emergent Adverse Events
Number of Subjects with Treatment Emergent Adverse Events
Time frame: Part A Days 0-10; Part B Days 0-12
Safety - Vital signs
Number of participants with clinically significant changes in vital signs
Time frame: Part A: Days (-1)-10;Part B: Days (-1)-12
Safety - Laboratory Parameters
Number of participants with clinically significant changes in laboratory assessments
Time frame: Part A: Days (-1)-10;Part B: Days (-1)-12
Safety - ECG change in QTcF
Number of subjects who had any increase in QTcF parameters.
Time frame: Part A: Days (-1)-10; Part B: Days (-1)-12
Pharmacokinetic - Maximum Concentration (Cmax)
Evaluation of Cmax in all cohorts of Part A, B and C.
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Time to maximum concentration (Tmax)
Evaluation of Tmax for Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Terminal Elimination Rate Constant (Kel)
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Evaluation of Kel in Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Terminal elimination half-life (t1/2)
Evaluation of t1/2 in Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Area under the concentration-time curve from time 0 to 24 hour post dose (AUC0-24)
Evaluation of AUC (0-24) in Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Evaluation of AUC (0-t) in Part A and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Evaluation of AUC (0-inf) in Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Residual Area under the curve (AUC%extrap)
Evaluation of AUC%extrap in Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Apparent total body clearance (CL/F)
Evaluation of CL/F in Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Apparent Volume of Distribution (Vz/F)
Evaluation of Vz/F in Part A, Part B and Part C
Time frame: Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Area under the curve from time of first dose to 12 h post-dose (AUC0-12)
Evaluation of AUC0-12 in Part B
Time frame: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5
Pharmacokinetic - Area under the curve from time of second dose to 12 h post-dose (AUC12-24)
Evaluation of AUC12-24 in Part B
Time frame: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5
Pharmacokinetic - Apparent total body clearance at steady state (CLss/F)
Evaluation of Clss/F in Part B
Time frame: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5
Pharmacokinetic - Maximum Concentration (Cmax) - Bioavailability Ratio Fed/Fasted
Evaluation of Cmax Bioavailability Ratio Fed/Fasted in Part C
Time frame: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Area under the curve from the time of dosing to the time of the last measurable concentration (AUC 0-t) - Bioavailability Fed/Fasted Ratio
Evaluation of AUC0-t Bioavailability Ratio Fed/Fasted in Part C
Time frame: Predose and up to 16 samples over a 24 hour period post dose per treatment period.
Pharmacokinetic - Area under the concentration-time curve from time 0 to infinity(AUC0-inf) - Bioavailability Fed/Fasted Ratio
Evaluation of AUC0-inf Bioavailability Ratio Fed/Fasted in Part C
Time frame: Predose and up to 16 samples over a 24 hour period post dose per treatment period.