9 October 2018 - - Patient enrollment has been completed in the TIMES 2 trial of the Phase 3 registration program for Imeglimin, an investigational therapeutic agent for type 2 diabetes, in Japan, French biopharmaceutical company Poxel SA (Euronext POXEL - FR0012432516) said.

Referred to as TIMES (Trials of IMeglimin for Efficacy and Safety), the Imeglimin Phase 3 registration program in Japan includes three pivotal trials to evaluate the efficacy and safety of Imeglimin in over 1,100 patients.

The TIMES 2 trial is a 52-week, open-label, parallel-group study to assess the long-term safety and efficacy of Imeglimin in Japanese patients with type 2 diabetes.

In this trial, Imeglimin is administrated as a monotherapy or combination therapy to over 700 patients with existing hypoglycemic agents, including a DPP4 inhibitor, SGLT2 inhibitor, biguanide, sulphonylurea and GLP1 receptor agonist.

The TIMES programme is a joint development effort between Poxel and Sumitomo Dainippon Pharma. The companies entered into a strategic partnership in October 2017 for the development and commercialisation of Imeglimin in Japan, China, South Korea, Taiwan and nine other Southeast and East Asian countries.

Imeglimin is an orally-available drug candidate with a novel mechanism of action that has been observed in clinical studies to demonstrate glucose lowering benefits by simultaneously targeting all three key organs which play an important role in the treatment of type 2 diabetes: the liver, muscles and the pancreas.

Imeglimin has demonstrated in preclinical studies the potential to address mitochondrial dysfunction, which is believed to be at the core of type 2 diabetes pathophysiology. Imeglimin has completed Phase 1 and Phase 2 development in over 1,200 subjects in the US, Europe and Japan.

TIMES (Trials of Imeglimin for Efficacy and Safety), the Phase 3 program for Imeglimin for the treatment of type 2 diabetes in Japan, consists of three pivotal trials involving over 1,100 patients.

The TIMES programme includes the following three trials that will be performed using the dose of 1,000 mg twice daily.
TIMES 1 is a Phase 3, 24-week, double-blind placebo-controlled, randomized, monotherapy study to assess the efficacy, safety and tolerability of Imeglimin in Japanese patients with type 2 diabetes, using the change in HbA1c as the primary endpoint.

Secondary endpoints of the trial will include other standard glycemic and non-glycemic parameters.

TIMES 2 is a Phase 3, 52-week, open-label, parallel-group study to assess the long-term safety and efficacy of Imeglimin in Japanese patients with type 2 diabetes.

In this study, Imeglimin will be administrated orally as a monotherapy or combination therapy with existing hypoglycemic agents, including a DPP4 inhibitor, SGLT2 inhibitor, biguanide, sulphonylurea and GLP1 receptor agonist.

TIMES 3 is a Phase 3, 16-week, double-blind, placebo-controlled, randomized study with a 36-week open-label extension period to evaluate the efficacy and safety of Imeglimin in combination with insulin in Japanese patients with type 2 diabetes and inadequate glycemic control on insulin therapy.

Imeglimin is the first clinical candidate in a new chemical class of oral agents called Glimins by the World Health Organization. Imeglimin has a unique mechanism of action that targets mitochondrial bioenergetics.

Imeglimin acts on all three key organs which play an important role in the treatment of type 2 diabetes: the liver, muscles and the pancreas, and it has demonstrated glucose lowering benefits by increasing insulin secretion in response to glucose, improving insulin sensitivity and suppressing gluconeogenesis.

This MOA has the potential to prevent endothelial and diastolic dysfunction, which can provide protective effects on micro- and macro-vascular defects induced by diabetes.

It also has the potential for protective effect on beta-cell survival and function.

This unique MOA offers the potential opportunity for Imeglimin to be a candidate for the treatment of type 2 diabetes in almost all stages of the current anti-diabetic treatment paradigm, including monotherapy or as an add-on to other glucose lowering therapies.

Poxel uses its development expertise in metabolism to advance a pipeline of drug candidates focused on the treatment of metabolic disorders, including type 2 diabetes and non-alcoholic steatohepatitis.