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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01596504
First received: May 7, 2012
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

Primary Objective:

- To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg QD (once daily) 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 patients 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 a 8-week treatment period in patients 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
    • 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)

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: lixisenatide (AVE0010)
Drug: liraglutide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Three-parallel-group Study on Pharmacodynamic Effects of 8-week QD Treatment With Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change from baseline for area under the plasma glucose concentration time profile from time of standardized breakfast start (30 minutes after IMP injection =T0.5) until 4 hours later (T4.5) subtracting the pre-meal plasma glucose value [ Time Frame: up to 4h30 after study drug injection on Day-3 and Day 56 (10 timepoints) ] [ Designated as safety issue: No ]
    IMP (Investigational Medicinal Products)


Secondary Outcome Measures:
  • Change from baseline for AUC 0:30-5:30h: area under the glucagon concentration-time curve, from time of standardized breakfast start (30 min after IMP injection=T0.5) until 5 hours later (T5.5) subtracting the pre-meal values [ Time Frame: up to 5h30 after study drug injection on Day-3 and Day 56 (11 timepoints) ] [ Designated as safety issue: No ]
  • Change from baseline for AUC 0:30-5:30h: area under C-peptide concentration time curve, from time of standardized breakfast start (30 min after IMP injection=T0.5) until 5 hours later (T5.5) subtracting the pre-meal values [ Time Frame: up to 5h30 after study drug injection on Day-3 and Day 56 (11 timepoints) ] [ Designated as safety issue: No ]
  • From breath test analysis, change from baseline to Day 55 for gastric emptying coefficient (GEC) [ Time Frame: Day-4 and Day 55 (15 samples per evaluation day) ] [ Designated as safety issue: No ]
  • Number of patients with 2-hour post-prandial plasma glucose level <140 mg/dL [ Time Frame: Day-3 and Day 56 ] [ Designated as safety issue: No ]

Enrollment: 142
Study Start Date: May 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lixisenatide 20 µg
lixisenatide : 10 µg once a day for 2 weeks, then 20 µg once a day for 6 weeks on top of insulin glargine with or without metformin
Drug: lixisenatide (AVE0010)

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Active Comparator: liraglutide 1.2 mg
liraglutide : 0.6 mg once a day for 1 week, then 1.2 mg once a day for 7 weeks on top of insulin glargine with or without metformin
Drug: liraglutide

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Other Name: Victoza®
Active Comparator: liraglutide 1.8 mg
liraglutide: 0.6 mg once a day for 1 week, then 1.2 mg once a day for 1 week and 1.8 mg once a day for 6 weeks on top of insulin glargine with or without metformin
Drug: liraglutide

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Other Name: Victoza®

Detailed Description:

Up to 2-week Screening period

  • A run-in period of 12 week 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
  Eligibility

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

Inclusion criteria :

  • Patients 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/m2

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 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 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: NCT01596504

Locations
Germany
Investigational Site Number 276008
Berlin, Germany, 10117
Investigational Site Number 276006
Berlin, Germany, 14050
Investigational Site Number 276004
Kiel, Germany, 24105
Investigational Site Number 276002
Mainz, Germany, 55116
Investigational Site Number 276005
Mönchengladbach, Germany, 41061
Investigational Site Number 276007
München, Germany, 80636
Investigational Site Number 276003
Neu-Ulm, Germany, 89231
Investigational Site Number 276001
Neuss, Germany, 41460
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01596504     History of Changes
Other Study ID Numbers: PDY12625, 2012-000027-40, U1111-1124-1364
Study First Received: May 7, 2012
Last Updated: August 5, 2013
Health Authority: Germany: Ethics Commission

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glargine
Insulin
Metformin
Insulin, Long-Acting
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