This first-in-human clinical trial with a randomized, double-blind, placebo-controlled, dose-escalation study design is regarded as standard to test the safety, tolerability, and pharmacokinetics of KYN-5356. The study comprises 3 parts: Part 1: Single Ascending Dose study Part 2: Multiple Ascending Dose study Part 3: Food Effect study The aim of Parts 1 and 2 of the study is to evaluate the safety and tolerability following single and multiple ascending doses of KYN-5356. The secondary aim is to evaluate the pharmacokinetics (PK) of escalating single and multiple doses of KYN-5356. In Part 2, cerebrospinal fluid will be sampled to explore PK and pharmacodynamic effects of KYN-5356. The potential effect of food intake on the disposition of KYN-5356 following a single oral dose will be evaluated in Part 3. Part 3 is an open-label, randomized, 2 period, 2 sequence design.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
72
KYN-5356, oral tablet
placebo, oral tablet
Parexel Los Angeles Early Phase Clinical Unit
Glendale, California, United States
Treatment-Emergent Adverse Events
All cohorts
Time frame: Initiation of dosing through the last follow-up visit after the last dose, approximately 8 days in the MAD and 5 days after dosing in the SAD and the Food Effect parts of the study
PK parameters: Cmax [SAD]
Maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part.
Time frame: Baseline (predose) through 72 hours post dosing
PK parameters: tmax [SAD]
Time of maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part.
Time frame: Baseline (predose) through 72 hours post dosing
PK parameters: AUCinf [SAD]
Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time calculated using the linear-log trapezoidal rule. For each dose in SAD part.
Time frame: Baseline (predose) through 72 hours post dosing
PK parameters: Cmax on Day 1 [MAD]
Maximum plasma concentration determined directly from the concentration-time profile. For each dose in MAD part
Time frame: Baseline (predose) through 24 hours post first dosing
PK parameters: tmax on Day 1 [MAD]
Time of maximum plasma concentration determined directly from the concentration-time profile. For each dose in MAD part.
Time frame: Baseline (predose) through 24 hours post first dosing
PK parameters: Cmax,ss [MAD]
Maximum observed plasma concentration during a dosing interval at steady state. For each dose in MAD part.
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
PK parameters: tmax,ss [MAD]
Time of maximum plasma concentration determined directly from the concentration-time profile at steady state. For each dose in MAD part.
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
PK parameters: AUCtau on Days 1 and 7 [MAD]
Area under the concentration-time curve over the dosing interval. For each dose in MAD part
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
PK parameters: AUCinf [MAD]
Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time calculated using the linear-log trapezoidal rule. For each dose in MAD part.
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
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