Clinical trial NCT01596504: Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-05-11
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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

Eligibility 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.

Primary outcomes:
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
timeFrame: 0.5 (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
Secondary outcomes:
measure: Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours
timeFrame: 0.5 (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
measure: Number of Participants With 2-Hour Post-prandial Plasma Glucose (PPG) <7.77 (mmol/L) at Day 56
timeFrame: Day 56
measure: Change From Baseline to Day 56 in PPG Excursion
timeFrame: 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
measure: Change From Baseline to Day 56 in Fasting Plasma Glucose (FPG)
timeFrame: 0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on Day 56
measure: Change From Baseline to Day 56 in Average 7-Point Self-Monitored Plasma Glucose (SMPG)
timeFrame: 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
measure: Change From Baseline to Day 56 in Corrected C-Peptide AUC From Time 0.5 Hours to 5.5 Hours
timeFrame: 0.5 (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
measure: Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours
timeFrame: 0.5 (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
measure: Change From Baseline to Day 56 in HbA1c
timeFrame: Pre-dose (Hour 0) on Day 1 (Baseline) and Day 56
measure: Change From Baseline to Day 56 in Average Daily Insulin Glargine Dose
timeFrame: Day -7 (Baseline), Day 56
measure: Change From Baseline to Day 55 in Gastric Emptying Half Life (t1/2)
timeFrame: 0 (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
measure: Change From Baseline to Day 55 in Gastric Emptying Coefficient
timeFrame: 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
measure: Change From Baseline to Day 57/58 in 24-Hour Mean Heart Rate
timeFrame: Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/-1 (Baseline) and Day 57/58
measure: Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure
timeFrame: Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/ -1 (Baseline) and Day 57/58
measure: Change From Baseline to Day 57 in Body Weight
timeFrame: 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to study drug administration on Day 57
measure: Change From Baseline to Day 57 in Waist Circumference
timeFrame: 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to IMP administration on Day 57
measure: Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast
timeFrame: 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
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Investigational Site Number 276008
city: Berlin
country: Germany
facility: Investigational Site Number 276006
city: Kiel
country: Germany
facility: Investigational Site Number 276004
city: Mainz
country: Germany
facility: Investigational Site Number 276002
city: Mönchengladbach
country: Germany
facility: Investigational Site Number 276005
city: München
country: Germany
facility: Investigational Site Number 276007
city: Neu-Ulm
country: Germany
facility: Investigational Site Number 276003
city: Neuss
country: Germany
facility: Investigational Site Number 276001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Meier JJ, Rosenstock J, Hincelin-Mery 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.