臨床研究等提出・公開システム

A phase III, double-blind, insulin-combination therapy study of imeglimin (TIMES 3)

TIMES 3

215

Eligible patients were Japanese adults aged 20 years or older with type 2 diabetes and inadequate glycaemic control on a regimen of insulin monotherapy or insulin in combination with a stable dose of a single oral antidiabetic agent for at least 12 weeks prior to screening. Mean (SD) age was 58.4 years (10.3), with 71 (33%) elderly patients (>=65 years), and mean eGFR was 77.2 mL/min/1.73m2 (SD 13.0), with 30 (14%) CKD stage 1 patients and 185 (86%) CKD stage 2 patients. Mean baseline HbA1c was 8.79% (SD 0.77). Patients were mainly receiving a basal insulin regimen (70%) and were previously treated mainly with insulin monotherapy (80.5%).

A total of 215 patients were randomized (108 imeglimin: IME, 107 placebo: PLA). Of these, 214 patients received at least one dose of study medication, had at least one post-baseline HbA1c value, and were included in the modified intention-to-treat analysis. Of these patients, 208 (96.7%; 107 IME, 101 PLA) completed the 16-week double-blind period, and 197 (91.6%; 103 IME, 94 PLA) completed the 36-week open-label extension period.

During the 16-week double-blind treatment period, the proportion of patients reporting any AEs was similar in the two treatment groups. Most reported AEs were mild in severity and only two patients in the placebo group experienced one AE of severe intensity. One patient (0.9%) in the imeglimin group and three patients (2.8%) in the placebo group experienced at least one serious AE. Regarding the open-label treatment extension period (PLA/IME; 36 weeks of treatment) / whole study period (IME/IME; 52 weeks of treatment), most AEs were also mild in intensity and only one patient (0.9%) in the IME/IME group and three patients (3.0%) in the PLA/IME group experienced at least one AE of severe intensity. The number of patients experiencing hypoglycaemia was similar in the two treatment groups. In patients receiving imeglimin, all hypoglycaemic events were mild in severity; no episodes required assistance.

At Week 16, HbA1c had significantly decreased by 0.63% (95% confidence interval [CI] -0.78 to -0.49) with imeglimin versus a decrease of 0.03% (95% CI -0.18 to 0.12) with placebo. Compared with placebo, the adjusted mean difference in change from baseline HbA1c at Week 16 was -0.60% (95% CI -0.80 to -0.40; P < 0.0001). This decrease was sustained up to 52 weeks with a mean decrease of -0.64% (95% CI -0.82 to -0.46) versus baseline.

At week 16, an HbA1c concentration < 7.0% was achieved by significantly more patients (P = 0.045) in the imeglimin group (eight patients, 7.4%) compared with the placebo group (one patient, 0.9%). A relative HbA1c decrease of at least 7% from baseline HbA1c was also achieved by significantly more patients (P < 0.0001) in the imeglimin group (59 patients, 54.6%) versus the placebo group (22 patients, 20.8%). Switching from placebo to imeglimin at Week 16 was also associated with a reduction of 0.54% (95% CI -0.71 to -0.38) in HbA1c (PLA/IME group) after 36 weeks of added imeglimin treatment. At Week 52, nine patients (8.3%) in the IME/IME group and one patient (1.0%) in the PLA/IME group achieved an HbA1c < 7.0%. A relative decrease of at least 7% from baseline HbA1c was achieved by 63 patients (58.3%) in the IME/IME group and 46 (45.5%) in the PLA/IME group.

Imeglimin significantly improved HbA1c in Japanese patients with insufficiently controlled type 2 diabetes by insulin and had a similar safety profile to placebo. The efficacy of imeglimin on top of insulin was sustained for 52 weeks. Imeglimin represents a potential new treatment option for this population as add-on to insulin therapy.

Jan. 04, 2022

https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.14642

No

POXEL S.A.

https://www.poxelpharma.com/en_us/contact

POXEL S.A.

https://www.poxelpharma.com/en_us/contact

completed

Feb. 24, 2018

Interventional

A 16-week phase III, multi-center, randomized, double-blind, placebo-controlled study

treatment purpose

3

Main inclusion criteria:
1) Insulin treated patients with type 2 diabetes mellitus, diagnosed for at least 12 weeks
2) HbA1c >=7.5% and < 11.0%
5) Body Mass Index (BMI) >= 18.5

Main exclusion criteria:
1) Patients with type 1 diabetes mellitus, diabetes that is a result of pancreatic injury, or secondary forms of diabetes
2) History of diabetic ketoacidosis or hyperosmolar non-ketotic coma
3) Cardiovascular or cerebrovascular disease within 24 weeks (myocardial infarction, stroke, unstable angina etc.)
4) Uncontrolled high blood pressure
5) Severe impairment of hepatic function

Both

Type 2 Diabetes Mellitus

investigational material(s)
Generic name etc : PXL008
INN of investigational material : Imeglimin
Therapeutic category code : 396 Antidiabetic agents
Dosage and Administration for Investigational material : 1000 mg twice daily, oral

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : 396 Antidiabetic agents
Dosage and Administration for Investigational material : -

efficacy
HbA1c
To assess the change in HbA1c from baseline after 16 weeks of imeglimin treatment compared to placebo

safety
Safety and tolerability
To assess the safety and tolerability of imeglimin treatment for 52 weeks as long-term insulin-combination therapy

Dec. 27, 2017