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 |
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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 | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
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 investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg (once daily) QD as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucoseconcentration- time curve (AUC) after a standardized breakfast at the end of a 8- week treatment period in patients with type 2 diabetes mellitus (T2DM) not adequately controlled with insulin glargine (± metformin) |
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E.2.2 | Secondary objectives of the trial |
•To assess the effects of lixisenatide 20 μg QD as compared to liraglutide 1.2 QD or 1.8 mg QD after a 8-week treatment period in patients with T2DM not adequately controlled with insulin glargine (± metformin) on:
-Post-prandial C-peptide, glucagon and appetite perceptions after a standardized breakfast
-Appetite perceptions after standardized dinner
-Gastric emptying after a standardized labelled test meal
-Fasting plasma glucose, 24-hour plasma glucose profile
-HbA1c
-Insulin glargine dose
-7-point self monitored plasma glucose (SMPG)
-Body weight and waist circumference
-24-hour heart rate and blood pressure
• To assess lixisenatide and liraglutide safety and tolerability as add on treatment to insulin glargine (± metformin) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patients with T2DM diagnosed at least 1 year before the screening visit
•Treatment with neutral protamine hagedorn (NPH) or insulin glargine for at least 3 months and at a stable dose (±20%) of at least 10 IU/day (for at least 2 months prior to screening) alone or combined with a stable dose of metformin with without DPP-4 or sulfonylurea
•Glycosylated hemoglobin (HbA1c) ≥6.5 and ≤9.5%
• Body mass index (BMI) between 20 and 40 kg/m2 |
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E.4 | Principal exclusion criteria |
•Pregnant women or breastfeeding women
•Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to, gastroparesis and gastroesophageal reflux disease requiring medical treatment within 6 months prior to the time of screening
•Any previous treatment with lixisenatide or participation in a previous study with lixisenatide (AVE0010), and any previous treatment with liraglutide stopped for safety concern or lack of efficacy
•Allergic reaction to any GLP-1 agonist in the past (eg, exenatide) or to metacresol
•History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
•Personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline for area under the plasma glucose concentration time profile from time of standardized breakfast start (30 minutes after IMP injection =T0.5) until 4 hours later (T4.5) subtracting the pre-meal plasma glucose value |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to 4h30 after study drug injection on Day-3 and Day 56 (10 timepoints) |
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E.5.2 | Secondary end point(s) |
Change from baseline for AUC 0:30-5:30h: area under the glucagon concentration-time curve, from time of standardized breakfast start (30 min after IMP injection=T0.5) until 5 hours later (T5.5) subtracting the pre-meal values
Change from baseline for AUC 0:30-5:30h: area under C-peptide concentration time curve, from time of standardized breakfast start (30 min after IMP injection=T0.5) until 5 hours later (T5.5) subtracting the pre-meal values
From breath test analysis, change from baseline to Day 55 for gastric emptying coefficient (GEC)
Number of patients with 2-hour post-prandial plasma glucose level <140 mg/dL |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to 5h30 after study drug injection on Day-3 and Day 56 (11 timepoints)
Day-4 and Day 55 (15 samples per evaluation day)
Day-3 and Day 56 |
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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 | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |