Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM (LixiLan-O)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes

Treatments: Drug: Insulin glargine/lixisenatide Fixed Ratio Combination; Drug: Metformin; Drug: Insulin glargine (HOE901); Drug: Lixisenatide (AVE0010)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02058147

EFC12404

2013-003131-30 (EudraCT Number)

U1111-1148-4334 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

To compare the insulin glargine/lixisenatide fixed ratio combination to lixisenatide alone and to insulin glargine alone (on top of metformin treatment) in glycated hemoglobin (HbA1c) change from baseline to Week 30.

Secondary Objective:

To compare the overall efficacy and safety of insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine alone and to lixisenatide alone (on top of metformin treatment) over a 30 week treatment period in participants with type 2 diabetes.

Full description

Approximately 37 weeks including up to 6 weeks of screening, 30-week treatment period, and a 3 days follow-up period.

Enrollment: 1,170 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with type 2 diabetes mellitus diagnosed for at least 1 year before the screening visit, treated for at least 3 months prior to visit 1 with metformin alone or metformin and a second oral anti-diabetic treatment that could be a sulfonylurea, a glinide, a sodium glucose co-transporter-2 inhibitor or a di-peptidyl peptidase 4 (DPP-4) inhibitors, and who were not adequately controlled with this treatment.
• Signed written informed consent.

Exclusion criteria

• HbA1c at screening visit:

  • less than 7.5% or more than 10% for participants previously treated with metformin alone,
  • less than 7.0% or more than 9% for participants previously treated with metformin and a second oral anti-diabetic treatment.

• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.

• Use of oral glucose-lowering agents other than those stated in the inclusion criteria or any injectable glucose-lowering agents during the 3 months before screening.

• Previous Treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes, at the discretion of the trial physician).

• History of discontinuation of a previous treatment with a glucagon-like peptide (GLP-1) receptor agonist (GLP-1 RA) due to safety/tolerability issue or lack of efficacy.

• Participant who previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide fixed ratio combination or had previously received lixisenatide.

• Any contraindication to metformin use, according to local labeling.

• 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 (e.g, 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/m^2.

• At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range.

• At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN.

• At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L).

Exclusion Criteria for randomization at the end of the screening period:

• HbA1c less than 7% or above 10%;
• Fasting Plasma glucose above 250 mg/dL (13.9 mmol/L);
• Metformin maximal tolerated dose less than 1500 mg/day;
• Amylase and/or lipase more than 3 ULN.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,170 participants in 3 patient groups

Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)

Experimental group

Description:

FRC once daily (QD) for 30 weeks. Dose individually adjusted.

Treatment:

Drug: Metformin

Drug: Insulin glargine/lixisenatide Fixed Ratio Combination

Insulin Glargine

Active Comparator group

Description:

Insulin glargine QD for 30 weeks. Dose individually adjusted.

Treatment:

Drug: Metformin

Drug: Insulin glargine (HOE901)

Lixisenatide

Active Comparator group

Description:

Lixisenatide 10 mcg QD for 2 weeks, then 20 mcg QD (maintenance dose).

Treatment:

Drug: Metformin

Drug: Lixisenatide (AVE0010)