Evaluation of PXL065 - deuterium-stabilized (R)-pioglitazone in patients with NASH: A phase II randomized placebo-controlled trial (DESTINY-1).

Background & Aims: Pioglitazone (Pio) is efficacious in NASH, but its utility is limited by PPARγ-driven side effects. Pio is a mixture of two enantiomers (R, S). PXL065, deuterium-stabilized R-Pio, lacks PPARγ activity but retains non-genomic activity.

Phase 2 trial with imeglimin in patients with Type 2 diabetes indicates effects on insulin secretion and sensitivity.

Introduction: The aim of the present study was to evaluate the effect of 18-week monotherapy with imeglimin on glucose tolerance and on insulin secretion/sensitivity in type 2 diabetic (T2D) patients.

Methods: The study was an 18-week, double-blind clinical trial in T2D subjects previously treated with stable metformin therapy and washed out for 4 weeks. Subjects were randomized 1:1 to receive a 1500 mg bid of imeglimin or placebo.

Efficacy and safety of imeglimin add-on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES 3): A randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period.

Aims: To evaluate the efficacy and safety of imeglimin for up to 52 weeks as combination therapy with insulin in Japanese patients with type 2 diabetes.

Materials And Methods: This double-blind, randomized, parallel-group phase 3 trial was performed at 35 sites in Japan. Eligible patients were individuals aged ≥20 years with type 2 diabetes and inadequate glycaemic control with insulin.

Efficacy and Safety of Imeglimin Monotherapy Versus Placebo in Japanese Patients With Type 2 Diabetes (TIMES 1): A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 3 Trial.

Objective: The aim of this study was to investigate the efficacy and safety of imeglimin, the first in a new class of oral antidiabetic agent, in Japanese patients with type 2 diabetes.

Research Design And Methods: This was a double-blind, randomized, parallel-group, placebo-controlled phase 3 trial in 30 sites in Japan. Eligible participants were individuals aged ≥20 years with type 2 diabetes treated with diet and exercise, stable for ≥12 weeks prior to screening, and whose HbA was 7.

Bioavailability of a co-formulated combination of amodiaquine and artesunate under fed and fasted conditions. A randomised, open-label crossover study.

Objectives: To assess the effect of food on the pharmacokinetics of the anti-malarial amodiaquine (AQ, CAS 6398-98-7) and artesunate (AS, CAS 182824-33-5) and their active metabolites [desethylamodiaquine (DSA, CAS 81496-81-3) and dihydroartemisinin (DHA, CAS79352-78-6), respectively] in healthy volunteers.

Methods: In an open, two-way crossover study, 22 healthy male volunteers fasted overnight and were randomised to receive a single oral administration of 4 tablets of a fixed-dose combination containing 135 mg AQ and 50 mg AS in the absence or presence of a standardised high-fat breakfast, administered 30 min before drug administration. Blood samples were collected up to Day 10 and AQ, DSA, AS and DHA were assayed by an LC/MS/MS method.