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A phase III, open-label, monotherapy and combination therapy long-term study of imeglimin (TIMES 2)

TIMES 2

714

Japanese adults aged 20 years or older with type 2 diabetes were enrolled in this 52-week long-term study. Patients treated with diet/exercise alone or together with a single antidiabetic monotherapy were included in imeglimin long-term monotherapy or the long-term combination groups, respectively. Mean age ranged from 56.6 to 63.6 years. Baseline HbA1c ranged from 7.92% to 8.70%.

A total of 714 patients received the following treatments: imeglimin monotherapy (n=134), combination with an alpha-glucosidase inhibitor (AGI: n=64), biguanide (BIG: n=64), dipeptidyl peptidase-4 inhibitor (DPP4-I: n=63), glinide (GLIN: n=64), glucagon-like peptide 1 receptor agonist (GLP1-RA: n=70), sodium glucose cotransporter 2 inhibitor (SGLT2-I: n=63), sulphonylurea (SU: n=127) or thiazolidinedione (TZD: n=65). All patients received imeglimin 1000 mg BID orally for 52 weeks as mono- or combination therapy.

The percentage of patients experiencing at least one treatment emergent adverse event (TEAE) was 75.5%. Most of these events were mild or moderate in intensity. Serious TEAEs, none of them related to study drug, occurred in 5.6% of all patients. No clinically significant changes in ECG, vital signs, physical examination, or laboratory tests were noted in any groups.

At week 52, HbA1c decreased by 0.46% with imeglimin monotherapy, by 0.56% - 0.92% with imeglimin as oral combination therapy, and by 0.12% with injectable GLP1-RA combination therapy. The greatest net HbA1c reduction (0.92%) occurred in patients receiving DPP4-I in combination with imeglimin.

At week 52 of imeglimin long-term monotherapy, the percentage of patients achieving an HbA1c less than 7% and a relative decrease of at least 7% vs. baseline HbA1c were 40.3% and 48.6%, respectively. At week 52 of imeglimin long-term combination therapy, the percentage of patients achieving an HbA1c less than 7% ranged from 8.1% to 37.2%. The percentage of patients achieving a relative decrease of at least 7% of baseline HbA1c ranged from 26.6% to 66.5%.

Imeglimin provides well-tolerated long-term safety and efficacy in both mono- and oral combination therapy in Japanese patients with type 2 diabetes.

Dec. 06, 2021

https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14613

No

POXEL S.A.

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

CMIC Co., Ltd.

ClinicalTrialInformation@cmic.co.jp

completed

Jan. 12, 2018

Interventional

A 52-week phase III, open-label, parallel-group study

treatment purpose

3

Main inclusion criteria:
<Long-term monotherapy>
1) Patients with type 2 diabetes mellitus, diagnosed for at least 12 weeks
2) HbA1c >=7.0% and < 10.0%
<Long-term combination therapy>
3) Patients with type 2 diabetes mellitus, diagnosed for at least 24 weeks
4) HbA1c >=7.5% and < 10.5%
<Both>
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 :
Dosage and Administration for Investigational material : -

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

efficacy
HbA1c
To assess the change in HbA1c from baseline after 52 weeks of imeglimin treatment

Nov. 24, 2017