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: April 21, 2015
Last verified: April 2015

May 7, 2012
April 21, 2015
May 2012
July 2013   (final data collection date for primary outcome measure)
Change from baseline to Day 56 in plasma glucose corrected area under the plasma concentration - Time curve (AUC) from Time 0.5 hours to 4.5 hours. [ Time Frame: 0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast),0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 56 ] [ Designated as safety issue: No ]
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)
Complete list of historical versions of study NCT01596504 on ClinicalTrials.gov Archive Site
  • Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours [ Time Frame: 0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day-3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on day 56 ] [ Designated as safety issue: No ]
  • Change From Baseline to Day 56 in plasma glucose corrected AUC From Time 0.5 Hours to 5.5 Hours [ Time Frame: 0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day-3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on day 56 ] [ Designated as safety issue: No ]
  • Change From Baseline to Day 56 in corrected C-peptide AUC From Time 0.5 Hours to 5.5 Hours [ Time Frame: 0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day-3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug adminstration on day 56 ] [ Designated as safety issue: No ]
  • Change from baseline to Day 55 in gastric emptying coefficient [ Time Frame: 0 (7:30 clock time, prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5,5.5 hours on Day -4(baseline) and on day 55 ] [ Designated as safety issue: No ]
  • Change from baseline to Day 55 in gastric emptying half life (t1/2) [ Time Frame: 0 (7:30 clock time, prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5,5.5 hours on Day -4(baseline) and on day 55 ] [ Designated as safety issue: No ]
  • Number of patients with 2-hour post-prandial plasma glucose level <7.77 millimole per litre (mmol/l ) at day 56 [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
  • Change from baseline to day 56 in postprandial plasma glucose (PPG) excursion [ Time Frame: 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline)0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on day 56 ] [ Designated as safety issue: No ]
  • Change from baseline to day 56 in fasting plasma glucose (FPG) [ Time Frame: 0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on day 56 ] [ Designated as safety issue: No ]
  • Change From Baseline to Day 56 in Average 7 Point Self Monitored Plasma Glucose (SMPG) [ Time Frame: Before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime on Day-3 (baseline) and on Day 56. ] [ Designated as safety issue: No ]
  • Change from baseline to Day 56 in HbA1C [ Time Frame: Pre-dose (hour 0) on Day 1 (baseline) and Day 56 ] [ Designated as safety issue: No ]
  • Change from Baseline to Day 56 in average Insulin glargin dose [ Time Frame: Day-7 (baseline), Day 56 ] [ Designated as safety issue: No ]
  • Change from Baseline to day 57/58 in 24-hour mean heart rate [ Time Frame: Every 15 minutes from 07:00 clock time to 23:00 clock time (daytime) and every 30 minutes from 23:00 clock time to 07:00 clock time (nighttime) on Day-2/-1(baseline) and day 57/58 ] [ Designated as safety issue: No ]
  • Change from Baseline to day 57/58 in 24-hour mean systolic blood pressure and diastolic blood pressure [ Time Frame: Every 15 minutes from 07:00 clock time to 23:00 clock time (daytime) and every 30 minutes from 23:00 clock time to 07:00 clock time (nighttime) on Day-2/-1(baseline) and day 57/58 ] [ Designated as safety issue: No ]
  • Change from baseline to day 57 in body weight [ Time Frame: 0.5 hours prior to standardized breakfast (7:30 clock time) on Day -1(Baseline); 0.5 hours prior to study drug administration on Day 57 ] [ Designated as safety issue: No ]
  • Change from baseline to day 57 in waist circumference [ Time Frame: 0.5 hours prior to standardized breakfast (7:30 clock time) on Day -1(Baseline); 0.5 hours prior to IMP administration on Day 57 ] [ Designated as safety issue: No ]
  • Change From Baseline to Day 56 in The Cumulative Score Mean on The Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast [ Time Frame: 0.5 (8:00 clock time, prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours on Day-3;0 (prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56) ] [ Designated as safety issue: No ]
  • 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 ]
Not Provided
Not Provided
 
Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin
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

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)

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
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: lixisenatide (AVE0010)

    Pharmaceutical form:solution for injection

    Route of administration: subcutaneous

  • Drug: liraglutide

    Pharmaceutical form:solution for injection

    Route of administration: subcutaneous

    Other Name: Victoza®
  • 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
    Intervention: Drug: lixisenatide (AVE0010)
  • 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
    Intervention: Drug: liraglutide
  • 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
    Intervention: Drug: liraglutide
Meier JJ, Rosenstock J, Hincelin-Méry A, Roy-Duval C, Delfolie A, Coester HV, Menge BA, Forst T, Kapitza C. Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label Trial. Diabetes Care. 2015 Jul;38(7):1263-73. doi: 10.2337/dc14-1984. Epub 2015 Apr 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
142
July 2013
July 2013   (final data collection date for primary outcome measure)

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.

Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01596504
PDY12625, 2012-000027-40, U1111-1124-1364
No
Sanofi
Sanofi
Not Provided
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP