The goal of this study is to learn more about the study candidate drug, KAND145, when given to healthy volunteers. The study will consist of two parts. In Part 1, the goal is to find out if the study drug KAND145 is safe and tolerable after a single dose. First, a small group of participants will receive a liquid for swallowing containing a low dose of the study drug or a liquid for swallowing that does not contain any drug. If this is safe and tolerable, higher doses will be given to subsequent groups of participants. Additionally, the effect of food on the metabolism of the study drug will be studied. In Part 2, the goal is to find out how the body absorbs, distributes, and gets rid of the study drug when it is taken twice a day for 8 days. As in Part 1, first a liquid for swallowing containing a low dose of the study drug or a liquid for swallowing that does not contain any study drug will be given to a first group of participants; additional doses will then be given to subsequent groups of participants. Additionally, it will be studied if the study drug KAND145 affects the pharmacokinetics of the medicine midazolam.
This is a Phase 1, first-in-human (FIH), single-center, placebo-controlled, randomized, double-blind study in healthy subjects to evaluate safety, tolerability, PK, food effect (FE) and interaction with midazolam after oral single ascending dosing (SAD; Part 1 of the study) and multiple ascending dosing (MAD; Part 2 of the study) of KAND145. A Safety Review Committee (SRC) will evaluate safety data from each dose cohort before proceeding with the subsequent cohort. The study population will consist of healthy adult male and female volunteers. Up to 88 participants (up to 48 participants in Part 1, up to 40 participants in Part 2) are planned to be enrolled in the study, at one investigational site. Part 1: In this part, participants receive single doses of KAND145 or placebo. Four ascending dose levels (cohorts) are planned; this may be extended with up to 2 optional dosing cohorts. In one cohort, a potential food interaction will be studied in the FE-part. Part 2: In this part, participants receive KAND145 or placebo twice a day (BID) for 8 consecutive days. Two ascending dose levels (cohorts) are planned; this may be extended with up to 3 optional dose levels (cohorts). To find out whether KAND145 has an effect on CYP3A4-mediated drug metabolism, the interaction of KAND145/placebo with midazolam will be studied in two cohorts.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
50
In Part 1 of the study, single ascending doses of KAND145 will be administered; in Part 2 of the study, multiple ascending doses (BID for 8 days) of KAND145 will be administered.
Participants randomized to the placebo arms will receive placebo at the same dosing frequency as the experimental arms.
Clinical Research Services Turku - CRST Oy
Turku, Finland
Part 1: Safety - Adverse events
Frequency and severity of AEs will be determined.
Time frame: From dosing (Day 1) until last follow-up (10-14 days post-dosing)
Part 1: Safety - Vital signs
Measured by the occurrence of clinically abnormal vital signs. Unit of measure: percent change from baseline
Time frame: From dosing (Day 1) until last follow-up (10-14 days post-dosing)
Part 1: Safety - electrocardiogram (ECG)
Measured by the occurrence of clinically abnormal ECG. Unit of measure: percent change from baseline
Time frame: From pre-dose (within 60 minutes) until 24 hours post-dose
Part 1: Safety - Safety laboratory tests
Measured by the occurrence of clinically abnormal lab test results (routine clinical chemistry, haematology and urinalysis). Unit of measure: percent change from baseline.
Time frame: From screening until last follow-up (10-14 days after dosing)
Part 2: PK - Maximum plasma (peak) drug concentration (Cmax)
Assessed for KAND145 and KAND567(AM) during steady state.
Time frame: From pre-dose (within 60 minutes) until 24 hours post-dose
Part 2: PK - Time to reach Cmax following drug administration (tmax)
Assessed for KAND145 and KAND567(AM) during steady state.
Time frame: From pre-dose (within 60 minutes) until 24 hours post-dose
Part 2: PK - Area under plasma concentration-time curve AUCτ
Assessed for KAND145 and KAND567(AM) during steady state
Time frame: From pre-dose (within 60 minutes) until 24 hours post-dose
Part 2: PK - Average plasma drug concentration (Cave [AUCτ/12])
Assessed for KAND145 and KAND567(AM) during steady state
Time frame: From pre-dose (within 60 minutes) until 24 hours post-dose
Part 2: PK - Terminal half-life (t½z)
Assessed for KAND145 and KAND567(AM) during steady state.
Time frame: From pre-dose (within 60 minutes) until 24 hours post-dose
Part 1 - PK: Cmax
Assessed for KAND145 and KAND567(AM) after single doses.
Time frame: From Day 1 until 24 hours post-dose
Part 1 - PK: tmax
Assessed for KAND145 and KAND567(AM) after single doses.
Time frame: From Day 1 until 24 hours post-dose
Part 1 - PK: AUCinf
Assessed for KAND145 and KAND567(AM) after single doses.
Time frame: From Day 1 until 24 hours post-dose
Part 1 - PK: Cave (AUCinf/12 h)
Assessed for KAND145 and KAND567(AM) after single doses.
Time frame: From pre-dose (within 60 minutes) until 24 hours post-dose
Part 1 - PK: t1/2z
Assessed for KAND145 and KAND567(AM) after single doses.
Time frame: From Day 1 until 24 hours post-dose
Part 2 - Safety: AEs
Frequency and severity of AEs will be determined
Time frame: From the day before the first dose (Day -1) until last follow-up (10-14 days after the last dose)
Part 2 - Safety: Vital signs
Measured by occurrence of clinically abnormal vital signs. Unit of measure: percent change from baseline
Time frame: From the day before the first dose (Day -1) until Day 8
Part 2 - Safety: ECG
Measured by the occurrence of clinically abnormal ECG. Unit of measure: percent change from baseline
Time frame: From Day -1 until Day 8
Part 2: Safety - Safety laboratory tests
Measured by the occurrence of clinically abnormal lab test results (routine clinical chemistry, haematology and urinalysis). Unit of measure: percent change from baseline
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Time frame: From Day -1 until last follow-up (10-14 days after the last dose)
Part 2 - PK: Cmax for midazolam
Only applicable for participants in Cohort 2:1 and Cohort 2:2 that will participate in the midazolam-part of the study.
Time frame: From Day 1 until Day 9 of the midazolam-part of the study
Part 2 - PK: tmax for midazolam
Only applicable for participants in Cohort 2:1 and Cohort 2:2 that will participate in the midazolam-part of the study.
Time frame: From Day 1 until Day 9 of the midazolam-part of the study
Part 2 - PK: AUCinf for midazolam
Only applicable for participants in Cohort 2:1 and Cohort 2:2 that will participate in the midazolam-part of the study.
Time frame: From Day 1 until Day 9 of the midazolam-part of the study
Part 2 - PK: t½z for midazolam
Only applicable for participants in Cohort 2:1 and Cohort 2:2 that will participate in the midazolam-part of the study.
Time frame: From Day 1 until Day 9 of the midazolam-part of the study