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

NCT01596504 | Completed Phase 2 Results

• 3 other identifiers: PDY126252012-000027-40U1111-1124-1364
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 8

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).

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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

  Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 milligram per decilitre (mg/dL) with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\]) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours).

  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 (16)

• Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours

  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

• Number of Participants With 2-Hour Post-prandial Plasma Glucose (PPG) <7.77 (mmol/L) at Day 56

  Day 56

• Change From Baseline to Day 56 in 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

• 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

• 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

Study Arms (3)

Lixisenatide 20 μg

EXPERIMENTAL

Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.

Drug: Lixisenatide (AVE0010); Drug: Insulin Glargine; Drug: Metformin

Liraglutide 1.2 mg

ACTIVE COMPARATOR

Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks under fasted conditions, on top of insulin glargine with or without metformin.

Drug: Liraglutide; Drug: Insulin Glargine; Drug: Metformin

Liraglutide 1.8 mg

ACTIVE COMPARATOR

Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.

Drug: Liraglutide; Drug: Insulin Glargine; Drug: Metformin

Interventions

Lixisenatide (AVE0010) DRUG

Pharmaceutical form: solution for injection self-administered with a pen-like injector (OptiClik®). Route of administration: subcutaneous

Lixisenatide 20 μg

Liraglutide DRUG

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Also known as: Victoza®

Liraglutide 1.2 mg; Liraglutide 1.8 mg

Insulin Glargine DRUG

Doses to be adjusted to maintain a fasting self-measured plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL)

Also known as: Lantus® SoloSTAR®

Liraglutide 1.2 mg; Liraglutide 1.8 mg; Lixisenatide 20 μg

Metformin DRUG

If previously taken metformin to be continued at stable dose throughout the study

Liraglutide 1.2 mg; Liraglutide 1.8 mg; Lixisenatide 20 μg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (8)

Investigational Site Number 276008

Berlin, 10117, Germany

Location

Investigational Site Number 276006

Berlin, 14050, Germany

Location

Investigational Site Number 276004

Kiel, 24105, Germany

Location

Investigational Site Number 276002

Mainz, 55116, Germany

Location

Investigational Site Number 276005

Mönchengladbach, 41061, Germany

Location

Investigational Site Number 276007

München, 80636, Germany

Location

Investigational Site Number 276003

Neu-Ulm, 89231, Germany

Location

Investigational Site Number 276001

Neuss, 41460, Germany

Location

Related Publications (1)

• 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.

  PMID: 25887358 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

lixisenatide; Liraglutide; Insulin Glargine; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 11, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: October 14, 2016
• Results First Posted: October 14, 2016

Record last verified: 2016-08

Locations

DE (8)