NCT00763451

Brief Summary

The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to metformin, over a period of 24 weeks of treatment, followed by an extension. The primary objective is to assess the effects of lixisenatide when added to metformin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction when it is used in two steps dose titration regimen at Week 24. Secondary objectives are to assess the effects of lixisenatide when added to metformin on glycemic control in comparison to placebo in terms of HbA1c reduction when it is used in a one-step dose titration regimen, the percentage of patients with HbA1c less than 7 percent or less than or equal to 6.5%, body weight, fasting plasma glucose (FPG); to assess the safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
484

participants targeted

Target at P50-P75 for phase_3 diabetes-mellitus-type-2

Timeline
Completed

Started Sep 2008

Typical duration for phase_3 diabetes-mellitus-type-2

Geographic Reach
15 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2008

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

September 30, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 1, 2008

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2011

Completed
6 years until next milestone

Results Posted

Study results publicly available

December 14, 2016

Completed
Last Updated

December 14, 2016

Status Verified

October 1, 2016

Enrollment Period

2.3 years

First QC Date

September 30, 2008

Results QC Date

August 18, 2016

Last Update Submit

October 21, 2016

Conditions

Diabetes Mellitus, Type 2

Keywords

hyperglycemia, GLP-1

Outcome Measures

Primary Outcomes (1)

  • Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24

    Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol

    Baseline, Week 24

Secondary Outcomes (5)

  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

    Baseline, Week 24

  • Change From Baseline in Body Weight at Week 24

    Baseline, Week 24

  • Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24

    Week 24

  • Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24

    Week 24

  • Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period

    Baseline up to Week 24

Other Outcomes (2)

  • Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24

    Baseline, Week 24

  • Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia

    First dose of study drug up to 3 days after the last dose administration, for up to 112 weeks

Study Arms (4)

Lixisenatide (Two-Step Titration)

EXPERIMENTAL

2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.

Drug: Lixisenatide (AVE0010)Device: Pen auto-injectorDrug: Metformin

Lixisenatide (One-Step Titration)

EXPERIMENTAL

1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to the end of treatment.

Drug: Lixisenatide (AVE0010)Device: Pen auto-injectorDrug: Metformin

Placebo (Two-Step Titration)

PLACEBO COMPARATOR

2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.

Drug: PlaceboDevice: Pen auto-injectorDrug: Metformin

Placebo (One-Step Titration)

PLACEBO COMPARATOR

1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, then 20 mcg QD up to the end of treatment.

Drug: PlaceboDevice: Pen auto-injectorDrug: Metformin

Interventions

Lixisenatide (AVE0010)DRUG

Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Lixisenatide (One-Step Titration)Lixisenatide (Two-Step Titration)
PlaceboDRUG

Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Placebo (One-Step Titration)Placebo (Two-Step Titration)
Pen auto-injectorDEVICE
Also known as: OptiClik®
Lixisenatide (One-Step Titration)Lixisenatide (Two-Step Titration)Placebo (One-Step Titration)Placebo (Two-Step Titration)
MetforminDRUG

Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.

Lixisenatide (One-Step Titration)Lixisenatide (Two-Step Titration)Placebo (One-Step Titration)Placebo (Two-Step Titration)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (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, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/day for at least 3 months prior to screening visit

You may not qualify if:

  • HbA1c less than (\<) 7% or greater than (\>) 10% at screening
  • At the time of screening age \<legal age of majority
  • Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
  • Type 1 diabetes mellitus
  • Treatment with an antidiabetic pharmacological agent other than metformin within the 3 months preceding the screening
  • FPG at screening \>250 milligram per deciliter (mg/dL) (\>13.9 millimole per liter \[mmol/L\])
  • Body mass index less than or equal to (\<)20 kilogram per square meter (kg/m\^2)
  • Weight change of more than 5 kg during the 3 months preceding the screening visit
  • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
  • History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
  • Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
  • Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
  • Known history of drug or alcohol abuse within 6 months prior to the time of screening
  • Cardiovascular, hepatic, neurological, 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, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
  • Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic or diastolic blood pressure \>180 millimeter of mercury (mmHg) or \>95 mmHg, respectively
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Administrative Office

São Paulo, Brazil

Location

Sanofi-Aventis Administrative Office

Santiago, Chile

Location

Sanofi-Aventis Administrative Office

Bogotá, Colombia

Location

Sanofi-Aventis Administrative Office

Tallinn, Estonia

Location

Sanofi-Aventis Administrative Office

Berlin, Germany

Location

Sanofi-Aventis Administrative Office

Milan, Italy

Location

Sanofi-Aventis Administrative Office

Vilnius, Lithuania

Location

Sanofi-Aventis Administrative Office

Kuala Lumpur, Malaysia

Location

Sanofi-Aventis Administrative Office

México, Mexico

Location

Sanofi-Aventis Administrative Office

Makati City, Philippines

Location

Sanofi-Aventis Administrative Office

Warsaw, Poland

Location

Sanofi-Aventis Administrative Office

Bucharest, Romania

Location

Sanofi-Aventis Administrative Office

Brastislava, Slovakia

Location

Sanofi-Aventis Administrative Office

Kiev, Ukraine

Location

Related Publications (3)

  • Bolli GB, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Wu Y, Hanefeld M. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med. 2014 Feb;31(2):176-84. doi: 10.1111/dme.12328. Epub 2013 Oct 24.

    PMID: 24117597RESULT

  • Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

    PMID: 39963952DERIVED

  • Ambery P, Donner TW, Biswas N, Donaldson J, Parkin J, Dayan CM. Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. Diabet Med. 2014 Apr;31(4):399-402. doi: 10.1111/dme.12361. Epub 2013 Dec 6.

    PMID: 24236828DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Hyperglycemia

Interventions

lixisenatideMetformin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic 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 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 30, 2008

First Posted

October 1, 2008

Study Start

September 1, 2008

Primary Completion

January 1, 2011

Study Completion

January 1, 2011

Last Updated

December 14, 2016

Results First Posted

December 14, 2016

Record last verified: 2016-10

Locations

PH(1)DE(1)UA(1)US(1)ES(1)PL(1)SL(1)ME(1)CO(1)RO(1)BR(1)LI(1)MY(1)CL(1)IT(1)