This is a Phase I study consisting of 2 parts: Part 1 aims to investigate the relative bioavailability of tablet formulation (test treatment) and Powder in capsule (PiC) formulation (reference treatment) of M7583 under fasted conditions. The aim of Part 2 is to determine and compare the single dose Pharmacokinetic (PK) profile of M7583 tablet under fasted and fed conditions to assess the food effect.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
18
Subject will receive either M7583 PiC or M7583 tablet formulation orally under fasted conditions in part 1 followed by M7583 tablet formulation under fed condition in part 2 of the study.
Nuvisan GmbH
Neu-Ulm, Bavaria, Germany
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concnetration (AUC0-t) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Maximum Observed Drug Concentration (Cmax) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Occurrence of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Up to Week 6
Occurrence of Subjects With TEAEs by Severity According to Qualitative Toxicity Scale Selected From National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Time frame: Up to Week 6
Number of Subjects with Clinically Significant Change From Baseline in Laboratory Tests, Vital Sign and 12-lead Electrocardiogram (ECG) Findings
Time frame: Up to Week 6
Time to Reach the Maximum Plasma Concentration (tmax) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Terminal Rate Constant (λz) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
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Apparent Terminal Half-life (t1/2) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Total Body Clearance of Drug From Plasma Following Oral Administration (CL/f) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Apparent Volume of Distribution (Vz/f) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Area Under the M7583 Plasma Concentration-time Curve From Time Zero to 24 hours After Dosing (AUC0-24h)
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Percentage of AUC0-∞ Obtained by Extrapolation (%AUCextra) of M7583
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Relative Bioavailability of M7583 Tablet versus M7583 PIC (Frel,T/P)
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
Relative Bioavailability of M7583 Tablet Administered 30 Minutes After a Standard Breakfast Versus Tablet Administered After an Overnight Fast (Frel,Fed/Fasted)
Time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period