Clinical Trials

Date: 2015-06-06

Type of information: Presentation of results at a congress

phase: 2b

Announcement: presentation of results at the American Diabetes Association Scientific Sessions

Company: Poxel (France)

Product: imeglimin

Action mechanism:

• glimin. Imeglimin is the first in a new chemical class of oral anti-diabetic agents, the glimins. Imeglimin acts on three main target organs involved in glucose homeostasis: the liver, the muscle, and the pancreas and has therefore a distinct mode of action compared to existing treatments for Type 2 diabetes. Imeglimin has shown a significant anti-diabetic efficacy combined with an excellent tolerance in earlier monotherapy clinical trials.

Disease: type 2 diabetes

Therapeutic area: Metabolic diseases

Country: Europe, USA

Trial details:

• The trial will assess the dose-response of Imeglimin at four dose levels compared to placebo in Type 2 diabetes patients after 24 weeks of treatment, using the change in glycosylated hemoglobin (HbA1c) as the primary endpoint. Over 350 patients are expected to be tested in the multi-center, double-blind, placebo-controlled, randomized study with five parallel groups, four imeglimin groups and one placebo group. Secondary endpoints of the trial include the optimal dose and activity of imeglimin compared to placebo on other glycemic and non-glycemic parameters. Furthermore, this phase IIb trial will assess the tolerability and safety of imeglimin compared to placebo.
• The main patient inclusion criteria for the trial are: either men or women aged between 18 and 75 years of age with Type 2 diabetes, who at the time of screening are either not on anti-diabetic agents or treated with oral anti-diabetic monotherapy, including metformin, sulfonylurea, dipeptidyl peptidase 4 (DPP- 4) inhibitors, glinide or acarbose. Some patients presenting with a mild to moderate renal impairment will also be recruited in the trial.

Latest news:

• • On June 6, 2015, Poxel presented data at the American Diabetes Association (ADA) 75th Scientific Sessions showing that its lead candidate, the first-in-class oral anti-diabetic agent Imeglimin, has met glycemic endpoints in a dose-ranging study conducted in 382 subjects, with a statistically significant reduction in the HbA1c (plasma glucose) of 0.63 percent. These results provide a full analysis of the trial’s top line data as announced in December 2014 and corroborate beneficial safety and tolerability data seen for Imeglimin in all previously conducted trials. The data were selected for presentation on a Guided Audio Poster Tour in addition to the main poster presentation.
• The study assessed the efficacy and tolerability of four doses of Imeglimin versus placebo in type 2 diabetes patients that were either naïve to treatment (25%) or previously managed with oral monotherapies (75%), mainly metformin. After a wash-out run-in period of three to six weeks, 382 subjects were randomized and treated for 24 weeks in a double-blind manner. The primary efficacy endpoint was the placebo-subtracted dose-dependent reduction in HbA1c from baseline. The study was conducted in eight countries, both in Europe and in the US. A statistically significant dose-dependent decrease in HbA1c (-0.63%, P<0.001) was observed, with the maximal effect being reached at the dose of 1500 mg twice daily after 18 weeks of treatment. Significant placebo-subtracted reductions in fasting plasma glucose (FPG) were also observed for the 1500 mg (–1.25 mmol/L or 22.5 mg/dL, P=0.001) and 2000 mg groups (–0.81 mmol/L or 14.6 mg/dL, P=0.029). A significantly greater proportion of patients achieved an HbA1c below 7% with in the 1500 mg group (33.3%, P=0.005), compared with placebo. No subjects required rescue treatment during the course of the study. All doses of Imeglimin were well tolerated with a safety profile comparable to placebo. No treatment-emergent serious adverse events related to Imeglimin or placebo were reported in the study at this dose.
• • On December 17, 2014, Poxel announced that imeglimin demonstrated dose-dependent efficacy on two key measures of diabetes control in a phase 2b trial conducted in both treatment-naïve patients and patients previously treated with a diabetes monotherapy. The trial achieved its primary endpoint of HbA1c reduction versus placebo (p<0.001), and significant decrease in FPG (Fasting Plasma Glucose) (p<0.006) at a dose of 1500mg, which will be the dose Poxel will advance into a phase 3 development program. This phase 2b trial assessed the efficacy and safety profile of 4 doses of Imeglimin in 382 patients after 24-week treatment. In addition to the HbA1C and FPG reductions obtained with the 1500mg dose, the number of responders (defined as patients achieving an HbA1C below 7% at the end of the treatment) was statistically significant (p=0.005) and no patient required rescue therapy (p=0.01) during the trial’s duration. The overall safety and tolerability profile was positive in all Imeglimin groups, with a similar overall incidence of adverse events between treatment groups and placebo group. The trial reported no serious adverse events related to the treatment with Imeglimin. Poxel anticipates reporting final analysis of the trial data at an international scientific meeting in 2015.
• • On March 7, 2013, Poxel has announced the initiation of a phase IIb clinical trial of imeglimin, a novel compound in development for type 2 diabetes.

Is general: Yes