E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 14.1 |
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 |
|
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 compare lixisenatide versus insulin glulisine in terms of HbA1c reduction and body weight change at week 26 in type 2 diabetic patients not adequately controlled on insulin glargine ± metformin. |
|
E.2.2 | Secondary objectives of the trial |
To compare the treatments/regimens on:
• The percentage of patients reaching the target of HbA1c <7% or ≤6.5%
• Body weight;
• Self-Monitored Glucose profiles
• Fasting Plasma Glucose (FPG)
• Post-prandial plasma glucose /glucose excursions during a standardized
meal test (subset of patients)
• Daily doses of insulins
• Safety and tolerability
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A randomized, open-label, active-controlled, 3-arm parallel-group, 26-week study comparing the efficacy and safety of lixisenatide to that of insulin glulisine once daily and insulin glulisine three times daily in patients with Type 2 diabetes insufficiently controlled with insulin glargine with or without metformin
EFC12626- Sub-study
Version 1
13 November 2012 |
|
E.3 | Principal inclusion criteria |
• Patients with type 2 diabetes mellitus diagnosed at least 1 year before screening visit (V1) .
• Patients treated with basal insulin for at least 6 months.
• Patients treated for at least 3 months prior to visit 1 with a stable basal insulin regimen (ie type of insulin and time/frequency of the injection). The insulin dose should be stable (± 20 %) and ≥20 U/day for at least 2 months prior to visit 1.
• Patients treated with basal insulin alone or in combination with 1 to 3 oral anti-diabetic drugs (OADs) that can be: metformin (≥1.5g/day or maximal tolerated dose), a sulfonylurea (SU), a dipeptidyl-peptidase-4 (DPP-4) inhibitor, a glinide. The dose of OADs should be stable for at least 3 months prior to visit 1.
|
|
E.4 | Principal exclusion criteria |
• At screening: age < legal age of majority
• At screening, HbA1c: < 7.5% and > 10.0% for patients treated with basal insulin alone or in combination with metformin only; < 7.0% and > 10.0% for patients treated with basal insulin and a combination of oral anti-diabetic drugs which includes a SU and/or a DPP4 inhibitor and/or a glinide
•Women of childbearing potential with no effective contraceptive method, pregnancy or lactation
• Type 1 diabetes mellitus
•Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria within 3 months prior to screening.
•Previous treatment with short or rapid acting insulin other than in relation to hospitalization or an acute illness.
•Any previous treatment with lixinatide, or any discontinuation from another GLP-1 receptor agonist due to safety/tolerability issue or lack of efficacy
•At screening, Body Mass Index (BMI) ≤20 or >40 kg/m².
•Weight change of more than 5 kg during the 3 months prior to the screening visit; use of weight loss drugs within 3 months prior to screening.
• Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures.
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.
• At screening resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 95 mmHg
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes)
• Contraindication related to metformin (for patient receiving this treatment), insulin glargine, insulin glulisine or lixisenatide.
• Patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease, if no treatment with metformin
• At screening, amylase and/or lipase > 3 times the upper limit of the normal laboratory range (ULN)
• At screening ALT or AST>3ULN
• At screening calcitonin ≥20 pg/ml (5.9 pmol/L)
Exclusion Criteria for randomization at the end of the screening period before randomization:
• HbA1c <7.0% or >9.0%.
• 7-day mean fasting SMPG >140 mg/dl (7.8 mmol/L).
• Amylase and/or lipase > 3 times ULN.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Change from baseline in HbA1c
- Change from baseline in body weight |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Percentage of patients reaching HbA1c <7%
- Percentage of patients reaching HbA1c ≤6.5%
- Change in body weight from baseline
- Percentage of patients with no weight gain.
- Change in 7-point SMPG profiles from baseline
- Change from baseline in FPG
- Change from baseline in post-prandial glucose /glucose excursions during a standardized meal test (subset of patients)
- Change from baseline in insulin glargine dose
- Daily dose of insulin glulisine
- Total daily dose of insulins
- Documented (PG <60 mg/dl) symptomatic hypoglycemia (percentage of subjects with at least one episode, number of events per patient-year)
- Severe hypoglycemia
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- week 26
- 26 weeks for:
Documented (PG <60 mg/dl) symptomatic hypoglycemia (percentage of subjects with at least one episode, number of events per patient-year)
and
Severe hypoglycemia
|
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 116 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Chile |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Italy |
Latvia |
Lithuania |
Netherlands |
Spain |
Mexico |
Poland |
Romania |
Russian Federation |
Slovakia |
Ukraine |
United Kingdom |
United States |
|
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
|
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 8 |