E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
adult-onset sugar diabetes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012607 |
E.1.2 | Term | Diabetes mellitus inadequate control |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
● To assess the effect of imeglimin versus placebo on glucose tolerance during a 3-hour Oral Glucose Tolerance Test (OGTT) after 18 weeks of treatment in type 2 diabetic subjects. |
|
E.2.2 | Secondary objectives of the trial |
● To assess the effect of imeglimin versus placebo on other glycemic parameters after 18 weeks of treatment in type 2 diabetic subjects:
o Fasting parameters, pre- and post-dose
o During a 3-hour OGTT
o During a 7-day Continuous Glucose Monitoring (CGM)
● To assess the effect of imeglimin versus placebo on other non-glycemic parameters after 18 weeks of treatment in type 2 diabetic subjects
● To assess the safety and tolerability of imeglimin versus placebo after 18 weeks of treatment in type 2 diabetic subjects
● To assess imeglimin pre- and post-dose concentration in the plasma during the course of the study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Subject has given written informed consent before any study-related activities are carried out;
● Male or female type 2 diabetic subjects treated with metformin monotherapy at stable dose (≥ 1500 mg/d) for at least 12 weeks prior to screening;
● HbA1c:
o between 7.2% and 9% at visit 1,
o between 7.5% and 9.5% at visit 3;
● Age: ≥ 18 to ≤ 75 years at visit 1;
● Body Mass Index (BMI): ≥ 25 to ≤ 40 kg/m² at visit 1;
● Creatinine clearance as estimated by the MDRD formula: ≥ 60 ml/min at visit 1;
● Effective contraception for women of child bearing potential at visit 1 up to the end of the study: female 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). |
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E.4 | Principal exclusion criteria |
● Subject with type 1 diabetes;
● Treatment with any other anti-diabetic treatment than metformin (except short use [i.e. 3 days maximum] of insulin in the dedicated context of a concomitant disease or surgical procedure) within 12 weeks before screening;
● Acute cardiovascular event within 6 months before screening (myocardial infarction, stroke). Revascularization within 3 months before screening;
● Uncontrolled high blood pressure (BP): diastolic ≥ 95 mm Hg or systolic ≥ 160 mm Hg with or without treatment;
● Impairment of hepatic function (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] ≥ 3 x the upper limit of normal);
● History of Torsade 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 in males and 470 ms in females on 2 different ECGs at screening visit 1 and/or pre-randomization visit 3, 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 screening. 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 placebo wash-out period);
● Pregnancy or lactation;
● Mental handicap, limited capacity, 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 allergy (e.g. anaphylactic, anaphylactoid reactions);
● Use of any non-permitted medication 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 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;
● Any disease which in the Investigator’s opinion would exclude the subject from the study;
● Participation in a clinical study within 30 days before screening;
● Participation in a previous clinical study using the same IMP imeglimin (EML017008-004, PXL008-002, PXL008-004 or PXL008-008). Subjects who were screen failed before randomization and have never received imeglimin are allowed to participate;
● Donation of blood or blood transfusion within 30 days before screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy objective of this study is to demonstrate a decrease in AUC glucose during the 3-hour OGTT from baseline visit 4 to end-of-treatment visit 8 with imeglimin versus placebo in subjects with type 2 diabetes mellitus after 18 weeks of treatment. This parameter will be assessed using Last Observation Carried Forward (LOCF) data for the ITT population, and using Observed Cases (OC) data for the ITT and PP populations. The analysis performed on the ITT population using LOCF data will be considered as primary. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline visit 4 to end-of-treatment visit 8 |
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E.5.2 | Secondary end point(s) |
Change from baseline to Week 18 in the following parameters:
● HbA1c
● Pre-dose fasting plasma glucose
● Post-dose fasting plasma glucose |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end-of-study is defined as the date of last visit of last subject participating in the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |