E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes Mellitus |
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E.1.1.1 | Medical condition in easily understood language |
Type II Diabetes Mellitus |
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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 | 17.0 |
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 demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination to insulin glargine in HbA1c change from baseline to week 30. |
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E.2.2 | Secondary objectives of the trial |
To compare the overall efficacy and safety of insulin glargine/lixisenatide fixed ratio combination to insulin glargine (with or without metformin) over a 30 week treatment period in patients with type 2 diabetes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Type 2 diabetes mellitus diagnosed at least 1 year before the screening visit.
•Treatment with basal insulin for at least 6 months before the screening visit.
• Stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection) for at least 3
months before the screening visit.
• Stable (plus/minus 20 percent) total daily basal insulin dose between 15 and 40U/day for at least 2 months prior to the screening visit.
• For patients receiving basal insulin AND 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s)
must be stable during the 3 months before the screening visit. The OADs can be 1 to 2 out of:
- metformin (more than or equal to1500mg/day or maximal tolerated dose),
- a sulfonylurea
- a glinide,
- a dipeptidyl-peptidase-4 inhibitor
- a sodium glucose co-transporter 2 inhibitor
• Fasting plasma glucose (FPG) less than or equal to 180 mg/dL(10.0 mmol/L) at screening visit for
patients receiving basal insulin in combination with 2 OADs or with 1 OAD other than metformin;
FPG less than or equal to 200 mg/dL (11.1 mmol/L) at screening visit for patients on basal insulin only or basal insulin plus metformin at screening visit,
• Signed written informed consent. |
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E.4 | Principal exclusion criteria |
• Age under legal age of adulthood at screening visit
• HbA1c at screening visit less than 7.5% or above 10%.
• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
• Use of other oral or injectable glucose-lowering agents than stated in the inclusion criteria in a
period of 3 months prior to screening.
• Previous use of insulin other than basal insulin e.g. prandial or pre-mixed insulin, in the year prior to screening. Note: Short term treatment (<or= 10 days) due to intercurrent illness is allowed.
• History discontinuation of a previous treatment with Glucagon Like Peptide -1 Receptor Agonists
for safety/tolerability or lack of efficacy.
• Patient who has previously participated in any clinical trial with lixisenatide or the insulin
glargine/lixisenatide fixed ratio combination or has previously received lixisenatide.
• Use of weight loss drugs within 3 months prior to screening visit.
• Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.
• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was
already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
• Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit
• At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m²
• At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN)
laboratory range,
• At screening visit ALT or AST more than 3 ULN
• At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L)
• Any contraindication to metformin use, according to local labeling, if the patient is taking
metformin.
• Patient who has a renal function impairment with creatinine clearance less than 30 mL/min (using the Cockroft and Gault formula) or end-stage renal disease for patients, not treated with metformin.
Exclusion criteria for randomization:
• HbA1c less than 7% or above 10% .
• Mean fasting Self Measured Plasma Glucose (SMPG) calculated from the self-measurements for 7 days the week before randomization visit is above 140 mg/dL (7.8 mmol/L).
• Average insulin glargine daily dose less than 20U or above 50U ( in the week before
randomization visit).
• Amylase and/or lipase more than 3 ULN |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from baseline |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Percentage of patients reaching HbA1c targets
- Change in 2-hour Post Prandial Glucose and in blood glucose excursion during standardized meal test from baseline to week 30
- Change in body weight from baseline
- Change in 7-point Self-Monitoring Plasma Glucose profiles from baseline
- Change in daily dose of insulin glargine from baseline
- Change in Fasting Plasma Glucose from baseline
- Documented (plasma glucose less than or equal to 70 mg/dl) symptomatic hypoglycemia
- Severe symptomatic hypoglycemia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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) | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
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 |
Australia |
Canada |
Chile |
Czech Republic |
Denmark |
Estonia |
Hungary |
Lithuania |
Mexico |
Netherlands |
Poland |
Romania |
Russian Federation |
Slovakia |
Spain |
Sweden |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 7 |
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 | 7 |