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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01596504
• Other study ID #: PDY12625
• Secondary ID: 2012-000027-40U1
• Status: Completed
• Phase: Phase 2
• First received: May 7, 2012
• Last updated: April 21, 2015
• Start date: May 2012
• Est. completion date: July 2013

Study information

• Verified date: April 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

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)

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• lixisenatide (AVE0010)
Pharmaceutical form:solution for injection Route of administration: subcutaneous
• liraglutide
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Locations

Country	Name	City	State
Germany	Investigational Site Number 276006	Berlin
Germany	Investigational Site Number 276008	Berlin
Germany	Investigational Site Number 276004	Kiel
Germany	Investigational Site Number 276002	Mainz
Germany	Investigational Site Number 276005	Mönchengladbach
Germany	Investigational Site Number 276007	München
Germany	Investigational Site Number 276003	Neu-Ulm
Germany	Investigational Site Number 276001	Neuss

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		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	No
Secondary	Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours		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	No
Secondary	Change From Baseline to Day 56 in plasma glucose corrected AUC From Time 0.5 Hours to 5.5 Hours		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	No
Secondary	Change From Baseline to Day 56 in corrected C-peptide AUC From Time 0.5 Hours to 5.5 Hours		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	No
Secondary	Change from baseline to Day 55 in gastric emptying coefficient		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	No
Secondary	Change from baseline to Day 55 in gastric emptying half life (t1/2)		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	No
Secondary	Number of patients with 2-hour post-prandial plasma glucose level <7.77 millimole per litre (mmol/l ) at day 56		Day 56	No
Secondary	Change from baseline to day 56 in postprandial plasma glucose (PPG) excursion		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	No
Secondary	Change from baseline to day 56 in fasting plasma glucose (FPG)		0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on day 56	No
Secondary	Change From Baseline to Day 56 in Average 7 Point Self Monitored Plasma Glucose (SMPG)		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.	No
Secondary	Change from baseline to Day 56 in HbA1C		Pre-dose (hour 0) on Day 1 (baseline) and Day 56	No
Secondary	Change from Baseline to Day 56 in average Insulin glargin dose		Day-7 (baseline), Day 56	No
Secondary	Change from Baseline to day 57/58 in 24-hour mean heart rate		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	No
Secondary	Change from Baseline to day 57/58 in 24-hour mean systolic blood pressure and diastolic blood pressure		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	No
Secondary	Change from baseline to day 57 in body weight		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	No
Secondary	Change from baseline to day 57 in waist circumference		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	No
Secondary	Change From Baseline to Day 56 in The Cumulative Score Mean on The Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast		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)	No