Effects of Lixisenatide Compared to Liraglutide on the Postprandial Plasma Glucose in Patients With Type 2 Diabetes

NCT01175473 | Completed Phase 2 Results

• 3 other identifiers: PDY109312009-017666-23U1111-1116-9040
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of the study is to compare the pharmacodynamic effects of lixisenatide (AVE0010), in comparison to liraglutide, as an add-on treatment to metformin, over a period of 4 weeks of treatment. The primary objective is to assess the effects of lixisenatide, in comparison to liraglutide, in reducing postprandial plasma glucose (PPG) assessed as area under the plasma glucose concentration curve (AUC) after a standardized breakfast at Week 4. The secondary objectives are to assess the effects of lixisenatide on the maximum PPG excursion, and on the changes in insulin, pro-insulin, C-peptide and glucagon plasma concentrations following a standardized breakfast, 24-hour profile of plasma glucose, glycosylated hemoglobin (HbA1c), satiety markers (obestatin, peptide YY \[PYY3-36\] and oxyntomodulin); and to assess the clinical and laboratory safety profile.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Area Under the Plasma Glucose Concentration Curve From Time 0.5 Hours to 4.5 Hours (GLU-AUC0:30-4:30h) at Day 28

  The area under the plasma glucose concentration time curve (GLU-AUC0:30-4:30h) was calculated using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\] on Day 28) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours). GLU-AUC0:30-4:30h on Day -1 was the baseline. Change in GLU-AUC0:30-4:30h = GLU-AUC0:30-4:30h on Day 28 minus GLU-AUC0:30-4:30h on Day -1.

  0.5 (8:00 clock time; prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

Secondary Outcomes (9)

• Change From Baseline in Postprandial Plasma Glucose (PPG) Excursion at Day 28

  0.5 (8:00 clock time; prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

• Change From Baseline in Pro-insulin AUC(0:30-4:30h) at Day 28

  0.5 (8:00 clock time; prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

• Change From Baseline in Insulin AUC(0:30-4:30h) at Day 28

  0.5 (8:00 clock time; prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

• Change From Baseline in C-Peptide AUC(0:30-4:30h) at Day 28

  0.5 (8:00 clock time; prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

• Change From Baseline in Glucagon AUC(0:30-4:30h) at Day 28

  0.5 (8:00 clock time; prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

Study Arms (2)

Lixisenatide

EXPERIMENTAL

1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD for up to Week 4.

Drug: Lixisenatide (AVE0010); Device: Pen auto-injector; Drug: Metformin

Liraglutide

ACTIVE COMPARATOR

2-step initiation regimen of liraglutide: 0.6 milligram (mg) QD subcutaneously for 1 week, followed by 1.2 mg QD for 1 week, then 1.8 mg QD up to Week 4.

Drug: Liraglutide; Device: Pre-filled pen injector; Drug: Metformin

Interventions

Lixisenatide (AVE0010) DRUG

Self administered by subcutaneous injections once daily 30 minutes before breakfast.

Lixisenatide

Pen auto-injector DEVICE

Also known as: OptiClik®

Lixisenatide

Liraglutide DRUG

Self administered by subcutaneous injections once daily 30 minutes before breakfast.

Liraglutide

Pre-filled pen injector DEVICE

Also known as: Victoza®

Liraglutide

Metformin DRUG

Metformin to be continued at stable dose (1.5 gram per day) up to Week 4.

Liraglutide; Lixisenatide

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes mellitus diagnosed for at least 1 year at the time of screening visit, not adequately controlled by metformin at a dose of at least 1.5 gram per day for at least 3 months prior to screening
• HbA1c greater than or equal to (\>=) 6.5% (as recommended by the American Diabetes Association) and HbA1c less than or equal to (\<=) 9% at screening
• Covered by Health Insurance System where applicable and/or in compliance with the recommendations of the National (German) Law in force relating to biomedical research
• Not under any administrative or legal supervision

You may not qualify if:

• At the time of screening age \<18 years or \>=75 years
• Body Mass Index (BMI): \<=20 kilogram per square meter (kg/m\^2) or \>=37 kg/m\^2
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
• Hemoglobinopathy or hemolytic anemia
• History of myocardial infarction, stroke, or heart failure requiring hospitalization within 6 months prior to the time of screening, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
• Cardiovascular, hepatic, neurological, or endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult (euthyroid patients on replacement therapy are to be included if the dosage of thyroxin is stable for at least 3 months prior to the screening visit)
• Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure \>160 millimeter of mercury (mmHg) or \>95 mmHg, respectively
• Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening that in the judgment of the investigator or any sub-investigator precludes safe completion of the study
• Receipt of blood or plasma products within 3 months prior to the time of screening
• Investigator or any sub-investigator, pharmacist, study coordinator, or their study staff or relative thereof directly involved in the conduct of the protocol
• Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility of meeting specific protocol requirements such as scheduled visits, being unable to do self-injections, etc.)
• Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin (for example, alpha glucosidase inhibitor, exenatide, dipeptidyl peptidase IV \[DPP-IV\] inhibitors, insulin, thiazolidinedione, sulfonylurea, etc.) within 3 months prior to the time of screening
• Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
• Likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol
• Use of any investigational drug within 3 months prior to screening

Sponsors & Collaborators

• Sanofi: lead

Study Sites (7)

Sanofi-Aventis Investigational Site Number 276006

Berlin, 14050, Germany

Location

Sanofi-Aventis Investigational Site Number 276004

Kiel, 24105, Germany

Location

Sanofi-Aventis Investigational Site Number 276002

Mainz, 55116, Germany

Location

Sanofi-Aventis Investigational Site Number 276003

Mannheim, 68167, Germany

Location

Sanofi-Aventis Investigational Site Number 276005

Mönchengladbach, 41061, Germany

Location

Sanofi-Aventis Investigational Site Number 276007

München, 80636, Germany

Location

Sanofi-Aventis Investigational Site Number 276001

Neuss, 41460, Germany

Location

Related Publications (1)

• Kapitza C, Forst T, Coester HV, Poitiers F, Ruus P, Hincelin-Mery A. Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin. Diabetes Obes Metab. 2013 Jul;15(7):642-9. doi: 10.1111/dom.12076. Epub 2013 Feb 25.

  PMID: 23368510 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

lixisenatide; Liraglutide; 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; Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Data for "Percentages of patients by ranges of oxyntomodulin levels" was reported instead of "Change from Baseline in oxyntomodulin concentration at Day 28" due to change in planned analysis as there were high numbers of values below the LOD.

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: August 2, 2010
• First Posted: August 4, 2010
• Study Start: August 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: November 28, 2016
• Results First Posted: October 11, 2016

Record last verified: 2016-10

Locations

DE (7)