Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin

Sanofi

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Lixisenatide (AVE0010); Drug: Metformin; Drug: Liraglutide; Drug: Insulin Glargine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01596504

2012-000027-40 (EudraCT Number)

U1111-1124-1364 (Other Identifier)

PDY12625

Details and patient eligibility

About

Primary Objective:

• To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg once daily (QD) as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucose-concentration-time curve (AUC) after a standardized breakfast at the end of a 8-week treatment period in participants with type 2 diabetes mellitus (T2DM) not adequately controlled with insulin glargine (± metformin).

Secondary Objectives:

• To assess the effects of lixisenatide 20 μg QD as compared to liraglutide 1.2 QD or 1.8 mg QD after an 8-week treatment period in participants with T2DM not adequately controlled with insulin glargine (± metformin) on:

  • Post-prandial C-peptide, glucagon and appetite perceptions after a standardized breakfast,
  • Appetite perceptions after standardized dinner,
  • Gastric emptying after a standardized labelled test meal,
  • Fasting plasma glucose, 24-hour plasma glucose profile,
  • Glycosylated hemoglobin (HbA1c),
  • Insulin glargine dose,
  • 7-point self monitored plasma glucose (SMPG),
  • Body weight and waist circumference,
  • 24-hour heart rate and blood pressure,

• To assess lixisenatide and liraglutide safety and tolerability as add on treatment to insulin glargine (± metformin).

Full description

Up to 2-week screening period

• A run-in period of 12 weeks at maximum including a forced titration with insulin glargine up to 11 weeks and 1 baseline pharmacodynamic assessment week
• A 8-week treatment(s) period(s) up to Day 57
• Follow-up: 7 ±2 days after the last treatment day
• Total study duration approximately 14 weeks up to 23 weeks

Enrollment: 142 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Participants with T2DM diagnosed at least 1 year before the screening visit.
• Treatment with neutral protamine hagedorn (NPH) or insulin glargine for at least 3 months and at a stable dose (±20%) of at least 10 IU/day (for at least 2 months prior to screening) alone or combined with a stable dose of metformin with or without dipeptidyl peptidase 4 (DPP-4) inhibitor or sulfonylurea.
• Glycosylated hemoglobin (HbA1c) ≥6.5 and ≤9.5%.
• Body mass index (BMI) between 20 and 40 kg/m^2.

Exclusion criteria:

• Pregnant women or breastfeeding women.
• 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 participation in a previous study with lixisenatide (AVE0010), and any previous treatment with liraglutide stopped for safety concern or lack of efficacy.
• Allergic reaction to any glucagon-like peptide-1 (GLP-1) agonist in the past (eg, 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.

The above information was 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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142 participants in 3 patient groups

Lixisenatide 20 μg

Experimental group

Description:

Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.

Treatment:

Drug: Lixisenatide (AVE0010)

Drug: Insulin Glargine

Drug: Metformin

Liraglutide 1.2 mg

Active Comparator group

Description:

Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks under fasted conditions, on top of insulin glargine with or without metformin.

Treatment:

Drug: Insulin Glargine

Drug: Liraglutide

Drug: Metformin

Liraglutide 1.8 mg

Active Comparator group

Description:

Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.

Treatment:

Drug: Insulin Glargine

Drug: Liraglutide

Drug: Metformin