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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01175473
First received: August 2, 2010
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

Primary Objective:

- To investigate the effects of lixisenatide as compared to liraglutide in reducing Postprandial Plasma Glucose (PPG) after a standardized breakfast in patients with type 2 diabetes

Secondary Objectives:

  • To assess the effects of lixisenatide as compared to liraglutide after a 4-week treatment period in patients with type 2 diabetes:

    • on the maximum PPG excursion, and on the changes in insulin, pro-insulin, C-peptide and glucagon plasma concentrations following a standardized breakfast
    • on the 24-h profile of plasma glucose
    • on Glycosylated hemoglobin (HbA1c)
    • on satiety markers (obestatin, PYY-36 and oxyntomodulin)
  • To assess the clinical and laboratory safety profile of lixisenatide and liraglutide over a 4-week treatment period in patients with type 2 diabetes

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Lixisenatide (AVE0010)
Drug: Liraglutide
Drug: Metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized 2-arm Parallel Group Study to Compare the Effects of 4-week QD Treatment With Lixisenatide or Liraglutide on the Postprandial Plasma Glucose in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Postprandial Plasma Glucose (PPG): change from baseline in area under curve AUC 0:30-4:30h [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Change from baseline in the area under the corrected (ie, relative to the premeal glucose concentration) plasma glucose concentration-time curve calculated using the linear trapezoidal rule (GLU-AUC 0:30-4:30), determined from glucose assessments on Day 28 from the time of standardized breakfast start (30 minutes after study medication injection) to 4 hours after injection


Secondary Outcome Measures:
  • Postprandial Plasma Glucose (PPG): change from baseline in PPG excursion [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Change from baseline in postprandial plasma glucose excursion (maximal postprandial change in plasma glucose) determined from the time of breakfast start (30 minutes after study medication injection) on Day 28 to 4 hours later, relative to the premeal plasma glucose concentration

  • Insulin plasma concentrations : change from baseline in area under curve AUC 0:30-4:30h [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Change from baseline in corrected (ie, relative to the premeal value) AUC 0:30-4:30 for the postprandial plasma concentrations for insulin determined from the time of standardized breakfast start (30 minutes after study medication injection) to 4 hours later on Day 28 (7-timepoint profile)

  • Pro-insulin plasma concentrations : change from baseline in area under curve AUC 0:30-4:30h [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Change from baseline in corrected (ie, relative to the premeal value) AUC 0:30-4:30 for the postprandial plasma concentrations for pro-insulin determined from the time of standardized breakfast start (30 minutes after study medication injection) to 4 hours later on Day 28 (7-timepoint profile)

  • C-peptide plasma concentrations : change from baseline in area under curve AUC 0:30-4:30h [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Change from baseline in corrected (ie, relative to the premeal value) AUC 0:30-4:30 for the postprandial plasma concentrations for C-peptide determined from the time of standardized breakfast start (30 minutes after study medication injection) to 4 hours later on Day 28 (7-timepoint profile)

  • Glucagon plasma concentrations : change from baseline in area under curve AUC 0:30-4:30h [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Change from baseline in corrected (ie, relative to the premeal value) AUC 0:30-4:30 for the postprandial plasma concentrations for glucagon determined from the time of standardized breakfast start (30 minutes after study medication injection) to 4 hours later on Day 28 (7-timepoint profile)

  • Glycosylated hemoglobin HbA1c : change from baseline to Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
  • Satiety markers (PYY-36, oxyntomodulin and obestatin): change from baseline to Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]

Enrollment: 148
Study Start Date: August 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lixisenatide
Lixisenatide will be uptitrated starting with 10 μg subcutaneous (s.c.) once daily (QD) for fourteen days and followed by fourteen days with 20 μg s.c. QD
Drug: Lixisenatide (AVE0010)

Pharmaceutical form:Solution for injection

Route of administration: subcutaneous

Drug: Metformin
continued at a stable dose throughout the study
Active Comparator: liraglutide
Liraglutide will be uptitrated starting with 0.6 mg s.c. once daily (QD) for seven days, followed by 1.2 mg s.c. once daily (QD) for seven days, and by fourteen days with 1.8 mg once daily (QD)
Drug: Liraglutide

Pharmaceutical form:Solution for injection

Route of administration: subcutaneous

Drug: Metformin
continued at a stable dose throughout the study

Detailed Description:

The duration of the study for each patient was 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 the last dose.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients with type 2 diabetes mellitus as defined by World Health Organization (fasting plasma glucose ≥ 7 mmol/L (126mg/dL) or 2 hours postprandial plasma glucose ≥ 11.1 mmol/L (200 mg/dL)), 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 g/day for at least 3 months prior to screening
  • Glycosylated hemoglobin HbA1c ≥ 6.5% (as recommended by the American Diabetes Association) and HbA1c ≤ 9% at screening

Exclusion criteria:

  • At the time of screening age < 18 years or ≥ 74 years
  • Body Mass Index (BMI) : ≤ 20 kg/m² or ≥ 37 kg/m²
  • Pregnant women or breast feeding women
  • Women of childbearing potential with no effective contraceptive method
  • Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin (e.g., alpha glucosidase inhibitor, exenatide, Dipeptidyl peptide IV (DPP-IV) inhibitors, insulin, thiazolidinedione (TZD), sulfonylurea (SU) etc.) within 3 months prior to the time of screening
  • Allergic reaction to any GLP-1 agonist in the past (e.g. 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01175473

Locations
Germany
Sanofi-Aventis Investigational Site Number 276006
Berlin, Germany, 14050
Sanofi-Aventis Investigational Site Number 276004
Kiel, Germany, 24105
Sanofi-Aventis Investigational Site Number 276002
Mainz, Germany, 55116
Sanofi-Aventis Investigational Site Number 276003
Mannheim, Germany, 68167
Sanofi-Aventis Investigational Site Number 276005
Mönchengladbach, Germany, 41061
Sanofi-Aventis Investigational Site Number 276007
München, Germany, 80636
Sanofi-Aventis Investigational Site Number 276001
Neuss, Germany, 41460
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01175473     History of Changes
Other Study ID Numbers: PDY10931, 2009-017666-23, U1111-1116-9040
Study First Received: August 2, 2010
Last Updated: October 22, 2012
Health Authority: Germany: Ethics Commission

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014