Phase 1 study evaluating the safety, tolerability, and pharmacokinetics of lobeglitazone administered as M107 Orally Disintegrating Tablet and Duvie tablet in healthy adult participants under fasted and fed conditions.
This is a Phase 1, single-center, parallel group study designed to determine the single-dose safety and PK profile of lobeglitazone from M107 ODT and Duvie, both administered orally in healthy adult volunteers. Participants will be enrolled in 1 of 3 cohorts conducted in parallel: Cohort 1 (Crossover): A single dose of Duvie oral tablet (0.415 mg; fasted) on Day 1 followed by a single dose of M107 ODT (0.4 mg; fasted) on Day 8, or vice versa, based on their random assignment with a 7-day washout between each dose. Cohort 2 (Crossover): M107 ODT (0.8 mg; fasted) followed by M107 ODT (0.8 mg; fed) after a 7-day washout. Cohort 3: M107 ODT (1.2 mg fasted) Participants in this cohort will receive M107 ODT 1.2 mg after a 10-hour fast. A total of up to 24 participants are planned to be enrolled, 8 in each cohort, in order to ensure 6 evaluable participants in each cohort. At least 2 males and 2 females are to be enrolled in each cohort.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Dosage form - Oral tablets Dosage - Duvie 0.415 mg and M107 ODT 0.4 mg Participants will receive each treatment once under fasted conditions in a randomized two-period crossover design.
Dosage form - Orally disintegrating tablet Dosage - 0.8 mg Participants will receive M107 once under fasted conditions and once after a high-fat, high-calorie meal in a two-period crossover design.
Dosage form - Orally disintegrating tablet Dosage - 1.2 mg Participants will receive a single oral dose of M107 under fasted conditions.
Nucleus Network Pty Ltd.
Melbourne, Victoria, Australia
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and clinically significant abnormalities
To assess the frequency and severity of TEAEs, SAEs, and any clinically significant changes in laboratory parameters, vital signs, electrocardiogram, and physical examination findings following administration of M107 Orally Disintegrating Tablet and Duvie.
Time frame: From screening to follow-up (up to Day 15 post-dose)
Maximum observed plasma concentration (Cmax)
To determine the peak plasma concentration of Lobeglitazone following oral administration of M107 Orally Disintegrating Tablet and Duvie.
Time frame: From pre-dose to 48 hours post-dose
Time to maximum observed plasma concentration (Tmax)
To assess the time it takes to reach the maximum plasma concentration of Lobeglitazone after administration.
Time frame: From pre-dose to 48 hours post-dose
Last measurable plasma concentration (Clast)
To evaluate the last quantifiable concentration of Lobeglitazone detected in plasma following administration.
Time frame: From pre-dose to 48 hours post-dose
Time of last measurable plasma concentration (Tlast)
To determine the time at which the last quantifiable plasma concentration of Lobeglitazone is observed.
Time frame: From pre-dose to 48 hours post-dose
Area under the concentration-time curve from 0 to 24 hours (AUC0-24h)
To evaluate the extent of Lobeglitazone exposure over the first 24 hours post-dose.
Time frame: From pre-dose to 24 hours post-dose
Area under the concentration-time curve from 0 to last measurable concentration (AUC0-last)
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To assess the total plasma exposure to Lobeglitazone from dosing until the last quantifiable concentration.
Time frame: From pre-dose to 48 hours post-dose
Area under the concentration-time curve extrapolated to infinity (AUCinf)
To estimate total drug exposure by including the extrapolated portion of the concentration-time curve.
Time frame: From pre-dose to 48 hours post-dose
Percentage of AUC extrapolated (%AUCexp)
Percentage of the total area under the plasma concentration-time curve from time zero to infinity (AUC₀-inf) that is extrapolated beyond the last measurable concentration (%AUCexp).
Time frame: From pre-dose to 48 hours post-dose
Terminal elimination half-life (t½)
To determine the time required for the plasma concentration of Lobeglitazone to decrease by half during the terminal elimination phase.
Time frame: From pre-dose to 48 hours post-dose
Apparent oral clearance (CL/F)
To assess the rate at which Lobeglitazone is eliminated from the plasma after oral administration.
Time frame: From pre-dose to 48 hours post-dose
Apparent volume of distribution (Vz/F)
To calculate the apparent volume in which Lobeglitazone is distributed throughout the body after oral administration.
Time frame: From pre-dose to 48 hours post-dose
Terminal elimination rate constant (λz or Kel)
To estimate the terminal elimination rate constant (λz or Kel) from the log-linear terminal phase of the plasma concentration-time curve following oral administration of lobeglitazone.
Time frame: From pre-dose to 48 hours post-dose.
Effect of food on maximum observed plasma concentration (Cmax) of Lobeglitazone
To compare the peak plasma concentration of Lobeglitazone after administration of M107 Orally Disintegrating Tablet under fasted versus fed conditions.
Time frame: From pre-dose to 48 hours post-dose
Effect of food on time to maximum observed plasma concentration (Tmax) of Lobeglitazone
To assess the difference in time to reach peak plasma concentration under fasted versus fed conditions following administration of M107 Orally Disintegrating Tablet.
Time frame: From pre-dose to 48 hours post-dose
Effect of food on total drug exposure (AUC0-last and AUCinf)
To evaluate the area under the concentration-time curve from time zero to last measurable concentration (AUC0-last) and extrapolated to infinity (AUCinf) for Lobeglitazone under fasted versus fed conditions.
Time frame: From pre-dose to 48 hours post-dose
Effect of food on terminal elimination half-life (t½)
To compare the terminal elimination half-life of Lobeglitazone under fasted and fed conditions following administration of M107 Orally Disintegrating Tablet.
Time frame: From pre-dose to 48 hours post-dose
Effect of food on apparent oral clearance (CL/F) and volume of distribution (Vz/F)
To evaluate differences in oral clearance and volume of distribution of Lobeglitazone when M107 Orally Disintegrating Tablet is administered under fed versus fasted conditions.
Time frame: From pre-dose to 48 hours post-dose
Effect of food on terminal elimination rate constant (λz or Kel) of lobeglitazone
To compare the terminal elimination rate constant (λz or Kel) of lobeglitazone under fasted and fed conditions following administration of the M107 Orally Disintegrating Tablet.
Time frame: From pre-dose to 48 hours post-dose.