Type 2 Diabetes Mellitus MedDRA version: 13.1 Level: PT Classification code 10012607 Term: Diabetes mellitus inadequate control System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: imeglimin
Product Code: PXL008
Pharmaceutical Form: Tablet
INN or Proposed INN: imeglimin
Current Sponsor code: PXL008
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
POXEL S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusions criteria at Visit 1 • Subject has given written informed consent before any study-related activities are carried out • Male or female type 2 diabetic subjects either o Naïve of treatment with an HbA1c = 8.5% and = 10.5% or o Inadequately controlled by metformin monotherapy at a dose = 1500 mg/day with an HbA1c = 7.5% and = 10% o Inadequately controlled by an alpha glucosidase inhibitor with an HbA1c and = 8% and = 10% o Inadequately controlled by a sulfonylurea or glinide with an HbA1c = 7.5% and = 10% • Age: = 18 to = 75 years • Body Mass Index (BMI): = 20 to = 40 kg/m² • No treatment with TZD or insulin (except short use of insulin in the dedicated context of a concomitant disease or surgery intervention) within 12 weeks before randomization • Creatinine clearance as estimated by the MDRD formula: = 60 ml/min • Permitted concomitant medication stable for at least 14 days before randomization • Effective contraception for women of child bearing potential Inclusion criteria at Visit 6 • Subject has given written informed consent before any study-related activities are carried out • Male or female type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy (100 mg per day) as defined by HbA1c = 7.5% • Monotherapy with sitagliptin stable for at least 12 weeks before randomization • HbA1c: = 7.5% and = 10% • Age: = 18 to = 75 years • Body Mass Index (BMI): = 20 to = 40 kg/m² • No treatment with TZD or insulin (except short use of insulin in the dedicated context of a concomitant disease or surgery intervention) within 12 weeks before randomization • Creatinine clearance as estimated by the MDRD formula: = 60 ml/min • Permitted concomitant medication stable for at least 14 days before randomization • Effective contraception for women of child bearing potential Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Any disease which in the investigator’s opinion would exclude the subject from the study • Uncontrolled high blood pressure (BP): diastolic = 95 mm Hg and systolic = 160 mm Hg • History of drug-induced Torsade de Pointe or presence of a familial long QT syndrome • Impairment of hepatic function (alkaline phosphatase [AP], aspartate aminotransferase [AST] or alanine aminotransferase [ALT] = 3 x the upper limit of normal) • Pregnancy or lactation • Mental handicap, legal incapacity, or any history of clinically important emotional and/or psychiatric illness • Presence of a contraindication to the investigational medication, including sitagliptin • Known hypersensitivity to any of the constituents or excipients of the study drug or history of relevant drug and/or food allergy (anaphylactic, anaphylactoid reactions) • Evidence of retinopathy of severity =35 in the Classification of Retinopathy Severity (as defined by the Early Treatment Diabetic Retinopathy Study and outlined in Appendix II) assessed by an ophthalmologist within 12 months before randomization. • Change in currently used medication and/or use of any new prescription or non-prescription medication within 14 days prior to randomization. The occasional use of paracetamol is authorized • Positive screen for hepatitis B surface antigen (HbsAg), antibody to the hepatitis A virus (Anti-HAV Immunoglobulin M), antibody to the hepatitis C virus (Anti-HCV), or antibodies to human immunodeficiency (Anti-HIV) 1 and 2 virus at screening • Any history of alcohol abuse or drug addiction • Participation in a clinical study within 60 days before randomization • Donation of blood within 30 days before randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect on glycemic efficacy using HbA1c as the primary evaluation criterion of 12-week treatment with imeglimin versus placebo add-on therapy in type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy;Secondary Objective: To assess the effect on other glycemic and non glycemic parameters of 12-week treatment with imeglimin versus placebo add-on therapy in type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy To assess the safety and tolerability of 12-week treatment with imeglimin versus placebo add-on therapy in type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy To assess imeglimin pre-dose concentration in the plasma at visits V7, V8 and V9 and 4-hour post-dose concentration at Visit 8 ;Primary end point(s): The primary assessment of efficacy will be made based on the change in HbA1c between Visit 6 (Baseline) and Visit 9 (Week 12). HbA1c will be measured from fasting blood samples collected at these time points. This parameter will be assessed both using the ITT and the PP populations and by LOCF and observed cases. ;Timepoint(s) of evaluation of this end point: Baseline to week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): HbA1c responder (Yes/No): defined as HbA1c = 7.0% at Week 12 - Change from baseline to Week 12 in fasting plasma glucose, insulin and c-peptide - Change from baseline to Week 12 in homeostasis model of insulin resistance and beta-cell function (HOMA-IR and HOMA-B) - Change from baseline to Week 12 in pro-insulin/insulin ratio - Change from baseline to Week 12 in total cholesterol, HDL-C and LDL-C - Change from baseline to Week 12 in triglycerides - Change from baseline to Week 12 in hsCRP, fibrinogen. - Percentage of subjects requiring rescue therapy any time between receiving first dose and Week 12. ;Timepoint(s) of evaluation of this end point: On V1, HbA1c, fasting plasma glucose, insulin and c-peptide, total cholesterol, triglycerides and hsCRP. On V3, V4 and V5: fasting plasma glucose and HbA1c. On V6 and V9: HbA1c, fasting plasma glucose and insulin, pro-insulin and c-peptide, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Apo B, hsCRP, fibrinogen. On V7: HbA1c, fasting plasma glucose and insulin, pro-insulin and c-peptide, triglycerides and hsCRP. On V8: HbA1c, fasting plasma glucose and insulin, pro-insulin and c-peptide, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and hsCRP. On V10: fasting plasma glucose, insulin and c-peptide, triglycerides, hsCRP | — |
Countries
Hungary, Latvia, Moldova, Republic of, Romania, Slovakia
Contacts
Public ContactPascale Fouqueray
POXEL S.A.
Outcome results
None listed