NCT00713830

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 sulfonylurea without or with 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 sulfonylurea with or without metformin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24. The secondary objectives are to assess the effects of lixisenatide on percentage of patients reaching HbA1c less than (\<) 7 percent (%); percentage of patients reaching HbA1c less than or equal to (\<=) 6.5%; body weight; fasting plasma glucose (FPG); beta-cell function assessed by homeostasis model assessment (HOMA) beta; 2-hour postprandial plasma glucose (PPG), glucagon, insulin, proinsulin, and C-peptide after a standardized meal challenge test in a sub-study in all patients in selected centers; to evaluate 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
859

participants targeted

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

Timeline
Completed

Started Jul 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

July 1, 2008

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

July 10, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 14, 2008

Completed
2.5 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

2.5 years

First QC Date

July 10, 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 Modified Intent-to-Treat (mITT) population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

    Baseline, Week 24

Secondary Outcomes (11)

  • Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24

    Baseline, Week 24

  • 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

  • Change From Baseline in Beta-cell Function Assessed by HOMA-beta at Week 24

    Baseline, Week 24

  • Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24

    Baseline, Week 24

  • +6 more secondary outcomes

Other Outcomes (4)

  • Change From Baseline in Glucose Excursion at Week 24

    Baseline, Week 24

  • Change From Baseline in Fasting Proinsulin-to-insulin Ratio and 2-hour Postprandial Proinsulin-to-insulin Ratio at Week 24

    Baseline, Week 24

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

    Baseline, Week 24

  • +1 more other outcomes

Study Arms (2)

Lixisenatide

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: SulfonylureaDrug: Metformin

Placebo

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: SulfonylureaDrug: Metformin

Interventions

Lixisenatide (AVE0010)DRUG

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

Lixisenatide
PlaceboDRUG

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

Placebo
Pen auto-injectorDEVICE
Also known as: OptiClik®
LixisenatidePlacebo
SulfonylureaDRUG

Sulfonylurea to be continued at maximum effective dose according to local labeling up to end of treatment.

LixisenatidePlacebo
MetforminDRUG

Metformin if given to be continued at stable dose (at least 1.5 gram per day \[except at least 0.75 gram per day in Japan and 1.0 gram per day in South Korea\]) up to the end of treatment.

LixisenatidePlacebo

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 before screening visit, insufficiently controlled with a sulfonylurea alone or a sulfonylurea in association with metformin

You may not qualify if:

  • HbA1c less than (\<) 7% or greater than (\>) 10% at screening
  • At the time of screening age less than legal age of majority
  • Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
  • Type 1 diabetes mellitus
  • Sulfonylurea less than the maximum effective dose according to local labeling
  • Sulfonylurea not at a stable (unchanged) dose for at least 3 months prior to screening
  • In case of treatment with metformin in association with sulfonylurea, no stable (unchanged) treatment with metformin of at least 1.5 gram per day (except at least 0.75 gram per day in Japan and at least 1.0 gram per day in South Korea), for at least 3 months prior to screening visit
  • FPG at screening \>250 milligram per deciliter (mg/dL) (\>13.9 millimole per liter \[mmol/L\])
  • History of hypoglycemia unawareness
  • Body mass index less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2)
  • Weight change of \>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
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Administrative Office

Sofia, Bulgaria

Location

Sanofi-Aventis Administrative Office

Prague, Czechia

Location

Sanofi-Aventis Administrative Office

Cairo, Egypt

Location

Sanofi-Aventis Administrative Office

Berlin, Germany

Location

Sanofi-Aventis Administrative Office

Mumbai, India

Location

Sanofi-Aventis Administrative Office

Netanya, Israel

Location

Sanofi-Aventis Administrative Office

Tokyo, Japan

Location

Sanofi-Aventis Administrative Office

Gouda, Netherlands

Location

Sanofi-Aventis Administrative Office

Bucharest, Romania

Location

Sanofi-Aventis Administrative Office

Moscow, Russia

Location

Sanofi-Aventis Administrative Office

Seoul, South Korea

Location

Sanofi-Aventis Administrative Office

Taipei, Taiwan

Location

Sanofi-Aventis Administrative Office

Bangkok, Thailand

Location

Sanofi-Aventis Administrative Office

Mégrine, Tunisia

Location

Sanofi-Aventis Administrative Office

Istanbul, Turkey (Türkiye)

Location

Related Publications (4)

  • Rosenstock J, Hanefeld M, Shamanna P, Min KW, Boka G, Miossec P, Zhou T, Muehlen-Bartmer I, Ratner RE. Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S). J Diabetes Complications. 2014 May-Jun;28(3):386-92. doi: 10.1016/j.jdiacomp.2014.01.012. Epub 2014 Jan 28.

    PMID: 24650952RESULT

  • Ahren B, Galstyan G, Gautier JF, Giorgino F, Gomez-Peralta F, Krebs M, Nikonova E, Stager W, Vargas-Uricoechea H. Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis. Diabetes Ther. 2016 Sep;7(3):583-90. doi: 10.1007/s13300-016-0179-6. Epub 2016 Jun 18.

    PMID: 27319011DERIVED

  • Yabe D, Ambos A, Cariou B, Duvnjak L, Evans M, Gonzalez-Galvez G, Lin J, Nikonova EV, de Pablos-Velasco P, Yale JF, Ahren B. Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse beta-cell function in the GetGoal-M and GetGoal-S trials. J Diabetes Complications. 2016 Sep-Oct;30(7):1385-92. doi: 10.1016/j.jdiacomp.2016.05.018. Epub 2016 May 24.

    PMID: 27267268DERIVED

  • Seino H, Onishi Y, Naito Y, Komatsu M. Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. Diabetol Metab Syndr. 2016 Jun 1;8:36. doi: 10.1186/s13098-016-0151-7. eCollection 2016.

    PMID: 27252787DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Hyperglycemia

Interventions

lixisenatideSulfonylurea CompoundsMetformin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic ChemicalsSulfonesSulfur CompoundsBiguanidesGuanidinesAmidines

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

July 10, 2008

First Posted

July 14, 2008

Study Start

July 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

US(1)RU(1)IL(1)DE(1)TU(1)IN(1)BU(1)NL(1)JP(1)KR(1)TH(1)CZ(1)EG(1)RO(1)TW(1)