Type 2 Diabetes Mellitus MedDRA version: 16.0 Level: PT Classification code 10012607 Term: Diabetes mellitus inadequate control System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Poxel S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subject has given written informed consent before any study-related activities are carried out • Male and female type 2 diabetic subjects, who at the time of screening are either: - Naïve of anti-diabetic agents (no treatment for 12 weeks) or - Treated with an oral anti-diabetic monotherapy, including metformin, sulfonylurea, dipeptidyl peptidase 4 (DPP-4) inhibitors, glinide or alpha-glucosidase inhibitor,, stable for 12 weeks • Age: = 18 to = 75 years at screening • Body mass index (BMI) : = 24 to = 40 kg/m² at screening • HbA1c criteria: - HbA1c = 7% and = 9.5% at Screening Visit 1 for subjects naïve of treatment - HbA1c = 6.5% and = 9% at Screening Visit 1 for subjects previously treated with an oral anti-diabetic monotherapy - HbA1c = 7% and = 9.5% at Visit 4 for both subjects naïve of treatment and previously treated with an oral anti-diabetic monotherapy • Creatinine clearance = 50 mL/[min*1.73 m2] at Screening Visit 1 and = 45 mL/[min*1.73 m2] at Visit 4, as estimated by the MDRD formula • Effective contraception for women of child bearing potential: females must have a negative pregnancy test and (if not surgically sterile or post-menopausal) practice acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception, sexual partner with non-reversed vasectomy [with azoospermia in 2 tests], 2 barrier methods [e.g., condom, diaphragm, or spermicide], or intrauterine device) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 700 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: • Any disease which in the Investigator’s opinion would exclude the subject from the study • Treatment with TZD, GLP-1 analogs or insulin (except short use of insulin in the dedicated context of a concomitant disease or surgical procedure) within 12 weeks before screening • Acute cardiovascular event within 3 months before randomization • Uncontrolled high blood pressure (BP): diastolic = 95 mm Hg or systolic = 160 mm Hg with or without treatment • Impairment of hepatic function (alkaline phosphatase [AP], aspartate aminotransferase [AST] or alanine aminotransferase [ALT] = 3 x the upper limit of normal) • History of drug-induced Torsades de Pointes (presence of a familial long QT syndrome, hypokalemia, heart failure…) or a marked baseline prolongation of the QTc interval (QTcF) greater than 450 ms on 2 different ECGs at either Screening Visit 1 or Laboratory Visit 4, or the use of at least 2 concomitant medications known to prolong the QTc interval. QTc will be calculated using the Fridericia’s formula. • Retinopathy of severity above mild non proliferative diabetic retinopathy assessed within 12 months before randomization (see classification in Appendix II of Protocol). In case no examination has been performed within the last 12 months, an ophthalmological examination is to be conducted prior to visit 2 (start of run-in) • Pregnancy or lactation • Mental handicap, legal incapacity, or any history of clinically important emotional and/or psychiatric illness • Known hypersensitivity to any of the constituents or excipients of the study drug, or history of relevant drug and/or food allergies (e.g. anaphylactic, anaphylactoid reactions) • Use of any non-permitted medication (described in Section 6.5.2 Non-Permitted Medicines of Protocol) starting from the signature of the informed consent. As far as possible concomitant medication should be stable • Positive screen for hepatitis B surface antigen (HbsAg), antibody to the hepatitis A virus (anti- HAV; immunoglobulin M [IgM]), antibody to hepatitis C virus (anti-HCV) in the context of positive circulating RNA or antibodies to human immunodeficiency virus (anti-HIV) 1 and 2 at screening • Any current history of alcohol abuse or drug addiction • Participation in a clinical study within 30 days before screening • Participation in a previous clinical study from the same Sponsor POXEL (PXL008-002 or PXL008-004) • Donation of blood or blood transfusion within 30 days before screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the dose-response of imeglimin at 4 doses (500 mg, 1000 mg, 1500 mg and 2000 mg bid) compared to placebo in male and female subjects with type 2 diabetes mellitus after 24 weeks of treatment, using glycosylated hemoglobin (HbA1c) as the primary evaluation criterion.;Secondary Objective: • To assess the optimal dose of imeglimin • To assess the activity of imeglimin compared to placebo on additional glycemic and non-glycemic parameters • To assess the tolerability and safety of imeglimin compared to placebo. • To investigate the pharmacokinetics (PK) / pharmacodynamics (PD) of imeglimin. ;Primary end point(s): The primary efficacy objective of this study is to demonstrate a dose-dependent response on HbA1c in subjects with type 2 diabetes mellitus after 24 weeks of imeglimin at 4 doses versus placebo, as evaluated by the mean change between Baseline (Visit 5) and week 24 (Visit 10) HbA1c. 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 (OC).;Timepoint(s) of evaluation of this end point: week 24 (compared with Baseline value at Visit 5) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy will be further assessed based on the following secondary variables: • Percentage of HbA1c responder (Yes/No): defined as HbA1c = 7.0% at Week 24 • Change from baseline to Week 24 in fasting plasma glucose, insulin and C-peptide • Change from baseline to Week 24 in homeostasis model of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) • Change from baseline to Week 24 in pro-insulin/insulin ratio • Change from baseline to Week 24 in total cholesterol, HDL-C and LDL-C • Change from baseline to Week 24 in triglycerides • Change from baseline to Week 24 in hsCRP • Percentage of subjects requiring rescue therapy any time between receiving first dose and Week 24.;Timepoint(s) of evaluation of this end point: For all secondary endpoints the timepoint of evaluation is week 24 when the change to Baseline (Visit 5) is assessed; Exception is the secondary endpoint assessing percentage of subjects requiring rescue therapy - this may occur any time between receiving first dose and Week 24. | — |
Countries
Estonia, Hungary, Latvia, Romania, Ukraine, United States
Contacts
Public ContactIwona Chylak
INC Research
Outcome results
None listed