Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (LixiLan) to Lixisenatide on Top of Oral Anti-diabetic Drugs (OADs) With Type 2 Diabetes in Japan (LIXILAN JP-O1)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Oral anti-diabetic drugs; Drug: Insulin glargine/Lixisenatide (HOE901/AVE0010); Drug: Lixisenatide (AVE0010)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02749890

U1111-1176-8357 (Other Identifier)

EFC14112

Details and patient eligibility

About

Primary Objective:

To compare LixiLan to lixisenatide in glycated hemoglobin (HbA1c) change from baseline to Week 26 in patients with type 2 diabetes mellitus.

Secondary Objective:

To compare the overall efficacy and safety of LixiLan to lixisenatide (with or without OADs) over a 52 week treatment period in patients with type 2 diabetes mellitus.

Full description

Approximately 55 weeks: an up-to 2-week screening period, a 26-week randomized open-label treatment period, a 26-week safety extension treatment period and a 3-day post-treatment safety follow up period.

Enrollment: 321 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Patient with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit, receiving 1 or 2 OADs that can be biguanide, thiazolidinedione, alpha-glucosidase-inhibitor, sodium glucose co-transporter 2 inhibitor; sulfonylurea, rapid-acting insulin secretagogue, or dipeptidyl-peptidase-4 inhibitor.
• Signed written informed consent.

Exclusion criteria:

• At the screening visit: age <20 years.
• At the screening visit: HbA1c <7.5% or >10%.
• At the screening visit: fasting plasma glucose (FPG) >250 mg/dL (13.8 mmol/L).
• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
• Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria during the 3 months before the screening visit.
• Previous treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes at the discretion of the trial physician).
• Laboratory findings at the screening visit, including:
• Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN),
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 ULN,
• Calcitonin ≥20 pg/mL (5.9 pmol/L),
• Positive serum pregnancy test.
• Contraindication to use of lixisenatide according to the local labeling. History of hypersensitivity to any glucagon-like peptide-1 receptor agonist (GLP-1RA) or to metacresol.
• Contraindication to use of insulin glargine according to the local labeling. History of hypersensitivity to insulin glargine or to any of the excipients.
• Patient who has a severe renal function impairment with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 or end-stage renal disease for patient not treated with metformin.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes).
• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.

The above information is not intended to contain all considerations relevant to a patient'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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321 participants in 2 patient groups

LixiLan

Experimental group

Description:

LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period.

Treatment:

Drug: Insulin glargine/Lixisenatide (HOE901/AVE0010)

Drug: Oral anti-diabetic drugs

lixisenatide

Active Comparator group

Description:

Lixisenatide (AVE0010) is injected subcutaneously (under the skin) once daily. It will be initiated with Dose 1 for 1 week and then continue with Dose 2 for 1 week followed by the maintenance dose of Dose 3 up to the end of treatment period. Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period.

Treatment:

Drug: Lixisenatide (AVE0010)

Drug: Oral anti-diabetic drugs