Effects of Lixisenatide Compared to Liraglutide on the Postprandial Plasma Glucose in Patients With Type 2 Diabetes

Sanofi

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Liraglutide; Drug: Metformin; Device: Pen auto-injector; Drug: Lixisenatide (AVE0010); Device: Pre-filled pen injector

Study type: Interventional

Funder types: Industry

Identifiers

NCT01175473

2009-017666-23 (EudraCT Number)

PDY10931

U1111-1116-9040 (Other Identifier)

Details and patient eligibility

About

The purpose of the study is to compare the pharmacodynamic effects of lixisenatide (AVE0010), in comparison to liraglutide, as an add-on treatment to metformin, over a period of 4 weeks of treatment.

The primary objective is to assess the effects of lixisenatide, in comparison to liraglutide, in reducing postprandial plasma glucose (PPG) assessed as area under the plasma glucose concentration curve (AUC) after a standardized breakfast at Week 4.

The secondary objectives are to assess the effects of lixisenatide on the maximum PPG excursion, and on the changes in insulin, pro-insulin, C-peptide and glucagon plasma concentrations following a standardized breakfast, 24-hour profile of plasma glucose, glycosylated hemoglobin (HbA1c), satiety markers (obestatin, peptide YY [PYY3-36] and oxyntomodulin); and to assess the clinical and laboratory safety profile.

Full description

The duration of the study for each patient is up to 7 weeks including a screening period up to 2 weeks, a treatment period of 4 weeks (Day 1 to Day 28), and an end-of-study visit 7 +/- 2 days after last study drug administration.

Enrollment: 148 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 diabetes mellitus diagnosed for at least 1 year at the time of screening visit, not adequately controlled by metformin at a dose of at least 1.5 gram per day for at least 3 months prior to screening
• HbA1c greater than or equal to (>=) 6.5% (as recommended by the American Diabetes Association) and HbA1c less than or equal to (<=) 9% at screening
• Covered by Health Insurance System where applicable and/or in compliance with the recommendations of the National (German) Law in force relating to biomedical research
• Not under any administrative or legal supervision

Exclusion criteria

• At the time of screening age <18 years or >=75 years
• Body Mass Index (BMI): <=20 kilogram per square meter (kg/m^2) or >=37 kg/m^2
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
• Hemoglobinopathy or hemolytic anemia
• History of myocardial infarction, stroke, or heart failure requiring hospitalization within 6 months prior to the time of screening, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
• Cardiovascular, hepatic, neurological, or endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult (euthyroid patients on replacement therapy are to be included if the dosage of thyroxin is stable for at least 3 months prior to the screening visit)
• Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure >160 millimeter of mercury (mmHg) or >95 mmHg, respectively
• Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening that in the judgment of the investigator or any sub-investigator precludes safe completion of the study
• Receipt of blood or plasma products within 3 months prior to the time of screening
• Investigator or any sub-investigator, pharmacist, study coordinator, or their study staff or relative thereof directly involved in the conduct of the protocol
• Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility of meeting specific protocol requirements such as scheduled visits, being unable to do self-injections, etc.)
• Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin (for example, alpha glucosidase inhibitor, exenatide, dipeptidyl peptidase IV [DPP-IV] inhibitors, insulin, thiazolidinedione, sulfonylurea, etc.) within 3 months prior to the time of screening
• Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
• Likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol
• Use of any investigational drug within 3 months prior to screening
• Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
• 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 liraglutide
• Allergic reaction to any glucagon like peptide - 1 (GLP-1) agonist in the past (for example, 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
• Known history of drug or alcohol abuse within 6 months prior to the time of screening
• Laboratory findings at the time of screening: alanine aminotransferase: >3 times the upper limit of the normal (ULN) laboratory range; calcitonin >=20 picogram per milliliter (pg/mL); amylase and lipase >3 times ULN; total bilirubin >1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100,000/mm^3; positive test for Hepatitis B surface antigen and/or Hepatitis C antibody and Positive reaction to tests for anti-human immunodeficiency virus (HIV) type 1 (HIV1) and anti-HIV2 antibodies
• Renal impairment defined by creatinine clearance <60 milliliter per minute (mL/min) using the Cockcroft-Gault formula

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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148 participants in 2 patient groups

Lixisenatide

Experimental group

Description:

1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD for up to Week 4.

Treatment:

Device: Pen auto-injector

Drug: Lixisenatide (AVE0010)

Drug: Metformin

Liraglutide

Active Comparator group

Description:

2-step initiation regimen of liraglutide: 0.6 milligram (mg) QD subcutaneously for 1 week, followed by 1.2 mg QD for 1 week, then 1.8 mg QD up to Week 4.

Treatment:

Device: Pre-filled pen injector

Drug: Liraglutide

Drug: Metformin