Safety, tolerability, pharmacokinetics (PK), cardiac conduction and food effect study on single and multiple ascending doses of KAR5585 in healthy adults.
The purpose of this study is to explore the safety, tolerability, pharmacokinetics (PK), and cardiac conduction effects of single and multiple ascending doses of KAR5585 in healthy adults. Food effect will also be evaluated after a single-dose administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
120
Single and multiple ascending doses of KAR5585 (100 mg initial dose)
Single and multiple ascending doses of placebo (100 mg initial dose)
Spaulding Clinical
West Bend, Wisconsin, United States
Number of participants with abnormal physical exam results
Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via physical examination.
Time frame: From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses
Number of participants with abnormal hematology values
Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via lab evaluation of hematology.
Time frame: From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses
Number of participants with abnormal electrocardiogram results
Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for abnormal ECG results.
Time frame: From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses
Number of participants with abnormal clinical chemistry values
Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via lab evaluation of clinical chemistries.
Time frame: From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses
Number of participants with abnormal urinalysis values
Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via lab evaluation of urinalysis.
Time frame: From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses
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Plasma area under the curve (AUC0-24) of prodrug KAR5585 and active inhibitor KAR5417 from time zero to 24 hours after dosing
Assessment of AUC 0-24 hours measured on Day 1, 7 and 14 when drug is dosed without a meal
Time frame: From 0-24 hours on Days 1, 7 and 14
Time to reach maximum observed plasma concentration (Tmax) of prodrug KAR5585 and active inhibitor KAR5417
Assessment of Tmax measured on Day 1, 7 and 14 when drug is dosed without a meal
Time frame: From 0-24 hours on Days 1, 7 and 14
Plasma terminal elimination half- life (T1/2) of prodrug KAR5585 and active inhibitor KAR5417
Assessment of T1/2 measured on Day 1, 7 and 14 when drug is dosed without a meal
Time frame: From 0-24 hours on Days 1, 7 and 14
Apparent volume of distribution (Vz/F) of prodrug KAR5585 and active inhibitor KAR5417
Assessment of Vz/F measured on Day 1, 7 and 14 when drug is dosed without a meal
Time frame: From 0-24 hours on Days 1, 7 and 14
Maximum peak concentration (Cmax) of prodrug KAR5585 and active inhibitor KAR5417
Assessment of Cmax measured on Day 1, 7 and 14 when drug is dosed without a meal
Time frame: From 0-24 hours on Days 1, 7 and 14
Serum levels of serotonin (ng/mL)
Serum serotonin (5-HT) levels will be measured to evaluate the pharmacodynamic effects of KAR5585 administration
Time frame: Days 1, 7 and 14
Urinary levels of 5-hydroxyindoleacetic acid(mg/24 hrs)
24 hour urine collection with analysis for 5-HIAA (5-hydroxyindoleacetic acid) levels.
Time frame: From 0-24 hours on Days 1, 7 and 14
Urinary levels of creatinine (gm/24 hrs)
24 hour urine collection with analysis for creatinine levels.
Time frame: From 0-24 hours on Days 1, 7 and 14
Urinary levels of 5-hydroxyindoleacetic acid normalized to creatinine (mg/gm)
24 hour urine collection with analysis for 5-HIAA (5-hydroxyindoleacetic acid). Urinary creatinine will be used to normalize urinary 5-HIAA levels: urinary 5-HIAA mg/gm creatinine
Time frame: From 0-24 hours on Days 1, 7 and 14
Plasma levels of 5-hydroxyindoleacetic acid (ng/mL)
Plasma 5-HIAA (5-hydroxyindoleacetic acid) levels will be measured to evaluate the pharmacodynamic effects of KAR5585 administration
Time frame: Days 1, 7 and 14
Plasma area under the curve (AUC0-24) of prodrug KAR5585 and active inhibitor KAR5417 from time zero to 24 hours after dosing
To determine the effect of food intake on the pharmacokinetics of KAR5585 and its active metabolite KAR5417, a cohort of patients will be studied after a single dose given fasting, followed by the same dose given with a high fat content food.
Time frame: From 0-24hrs on Days 1, 7 and 14
Time to reach maximum observed plasma concentration (Tmax) of prodrug KAR5585 and active inhibitor KAR5417
To determine the effect of food intake on the pharmacokinetics of KAR5585 and its active metabolite KAR5417, a cohort of patients will be studied after a single dose given fasting, followed by the same dose given with a high fat content food.
Time frame: From 0-24hrs on Days 1, 7 and 14
Plasma terminal elimination half-life (T1/2) of prodrug KAR5585 and active inhibitor KAR5417
To determine the effect of food intake on the pharmacokinetics of KAR5585 and its active metabolite KAR5417, a cohort of patients will be studied after a single dose given fasting, followed by the same dose given with a high fat content food.
Time frame: From 0-24hrs on Days 1, 7 and 14
Apparent volume of distribution (Vz/F) of prodrug KAR5585 and active inhibitor KAR5417
To determine the effect of food intake on the pharmacokinetics of KAR5585 and its active metabolite KAR5417, a cohort of patients will be studied after a single dose given fasting, followed by the same dose given with a high fat content food.
Time frame: From 0-24hrs on Days 1, 7 and 14
Maximum peak concentration (Cmax) of prodrug KAR5585 and active inhibitor KAR5417
To determine the effect of food intake on the pharmacokinetics of KAR5585 and its active metabolite KAR5417, a cohort of patients will be studied after a single dose given fasting, followed by the same dose given with a high fat content food.
Time frame: From 0-24hrs on Days 1, 7 and 14