The phase 1 portion of the study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TLC-6740 after single- and multiple-ascending doses in healthy subjects. The phase 1b portion of the study is designed to assess the safety, tolerability, and PK of TLC-6740 in subjects with obesity, with or without type 2 diabetes mellitus.
The primary objectives are to assess the safety, tolerability, and plasma PK of TLC-6740 in healthy subjects and subjects with obesity. The exploratory objective is to evaluate the PD of TLC-6740 in healthy subjects and subjects with obesity, with or without type 2 diabetes. This study is comprised of seven parts: Part A (single-ascending dose), Part B (multiple-ascending dose), Part C (adaptive single- and/or multiple-ascending dose), Part D (relative bioavailability of a tablet formulation of TLC-6740), Part E (drug-drug interaction study to determine the effect of TLC-6740 on drug metabolizing enzymes), Part F (multiple dose of TLC-6740 in subjects with obesity with or without type 2 diabetes mellitus), and Part G (multiple dose of TLC-6740 in subjects with obesity receiving tirzepatide). Up to 48, 50, 100, 8, and 28 healthy subjects will be recruited in Parts A, B, C, D, and E, respectively. Up to 180 and 150 obese subjects will be recruited in Parts F and G, respectively. The effect of food on TLC-6740 PK will also be evaluated in this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
564
Oral solution of TLC-6740
Placebo-to-match oral solution TLC-6740
Tablet formulation of TLC-6740
OrsoBio Auckland Research Site 1
Auckland, New Zealand
RECRUITINGOrsoBio Auckland Research Site 2
Auckland, New Zealand
RECRUITINGOrsoBio Auckland Research Site 3
Auckland, New Zealand
RECRUITINGIncidence of TLC-6740 treatment-emergent adverse events
Adverse events (AEs) - severity of the AEs will be graded using the Common Terminology Criteria for AE (CTCAE) (v5.0). The relationship between AEs and the study drug will be indicated as related or not related.
Time frame: Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
PK of TLC-6740 AUC
Area under the concentration-time curve
Time frame: Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
PK of TLC-6740 Cmax
Maximum plasma concentration
Time frame: Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
PK of TLC-6740 tmax
Time to reach Cmax
Time frame: Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
PK of TLC-6740 t1/2
Half-life
Time frame: Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
PK of TLC-6740 CL/F
Apparent clearance, calculated as dose/AUC0-inf
Time frame: Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
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Oral dose of omeprazole, voriconazole, itraconazole, or rifampicin
Subcutaneous injection of tirzepatide
Placebo-to-match tablet formulation of TLC-6740
OrsoBio Research Site
Christchurch, New Zealand
RECRUITING