GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Pioglitazone (GETGOAL-P)

A Randomized, Double-blind, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Main Treatment Period and an Extension Assessing the Efficacy and Safety of AVE0010 on Top of Pioglitazone in Patients With Type 2 Diabetes Not Adequately Controlled With Pioglitazone

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 pioglitazone with or without 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 pioglitazone on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.

Secondary objectives are to assess the effects of lixisenatide when added to pioglitazone on the percentage of patients reaching HbA1c less than 7 percent (%) and less than or equal to 6.5%, fasting plasma glucose (FPG), body weight, beta-cell function (assessed by homeostatic model assessment of beta-cell function [HOMA-beta]), and on fasting plasma insulin (FPI), to assess the safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Device: Pen auto-injector; Drug: Lixisenatide (AVE0010); Drug: Pioglitazone; Drug: Metformin; Drug: Placebo

Detailed Description

Patients who complete the 24-week main double-blind treatment would undergo a variable double-blind extension treatment, which ends for all patients at approximately the schedule date of Week 76 visit (Visit 25) for the last randomized patients.

• Study Type: Interventional
• Enrollment (Actual): 484
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Sanofi-Aventis Investigational Site Number 040706
  • Vienna, Austria, 1060
    • Sanofi-Aventis Investigational Site Number 040704
  • Wels, Austria, 4600
    • Sanofi-Aventis Investigational Site Number 040707
  • Wien, Austria, 1030
    • Sanofi-Aventis Investigational Site Number 040702
  • Wien, Austria, 1100
    • Sanofi-Aventis Investigational Site Number 040701
  • Wien, Austria, 1100
    • Sanofi-Aventis Investigational Site Number 040705
• Canada
  • London, Canada, N6A 5R8
    • Sanofi-Aventis Investigational Site Number 124710
  • Mirabel, Canada, J7J 2K8
    • Sanofi-Aventis Investigational Site Number 124712
  • Saskatoon, Canada, S7K 3H3
    • Sanofi-Aventis Investigational Site Number 124703
  • Scarborough, Canada, M1E 5E9
    • Sanofi-Aventis Investigational Site Number 124713
  • Sherbrooke, Canada, J1H 5N4
    • Sanofi-Aventis Investigational Site Number 124711
  • Smiths Falls, Canada, K7A 4W8
    • Sanofi-Aventis Investigational Site Number 124704
  • St-Romuald, Canada, G6W 5M6
    • Sanofi-Aventis Investigational Site Number 124705
  • Sudbury, Canada, P3E 2P2
    • Sanofi-Aventis Investigational Site Number 124716
  • Thornhill, Canada, L4J 8L7
    • Sanofi-Aventis Investigational Site Number 124701
  • Vancouver, Canada, V5Z 1C6
    • Sanofi-Aventis Investigational Site Number 124708
• France
  • Armentieres, France, 59427
    • Sanofi-Aventis Investigational Site Number 250704
  • La Rochelle Cedex, France, 17019
    • Sanofi-Aventis Investigational Site Number 250707
  • Labarthe Sur Leze, France, 31860
    • Sanofi-Aventis Investigational Site Number 250705
  • Le Creusot, France, 71200
    • Sanofi-Aventis Investigational Site Number 250702
  • Strasbourg, France, 67091
    • Sanofi-Aventis Investigational Site Number 250701
• Germany
  • Asslar, Germany, 35614
    • Sanofi-Aventis Investigational Site Number 276708
  • Berlin, Germany, 10115
    • Sanofi-Aventis Investigational Site Number 276704
  • Künzing, Germany, 94550
    • Sanofi-Aventis Investigational Site Number 276703
  • Leipzig, Germany, 04103
    • Sanofi-Aventis Investigational Site Number 276706
  • Pirna, Germany, 01796
    • Sanofi-Aventis Investigational Site Number 276707
  • Sulzbach-Rosenberg, Germany, 92237
    • Sanofi-Aventis Investigational Site Number 276702
  • Würzburg, Germany, 97072
    • Sanofi-Aventis Investigational Site Number 276701
• Greece
  • Athens, Greece, 10552
    • Sanofi-Aventis Investigational Site Number 300705
  • Athens, Greece
    • Sanofi-Aventis Investigational Site Number 300703
  • Athens, Greece
    • Sanofi-Aventis Investigational Site Number 300704
  • Thessaloniki, Greece, 56429
    • Sanofi-Aventis Investigational Site Number 300701
• Guatemala
  • Guatemala, Guatemala, 01010
    • Sanofi-Aventis Investigational Site Number 320702
  • Guatemala, Guatemala, 01014
    • Sanofi-Aventis Investigational Site Number 320701
  • Guatemala, Guatemala
    • Sanofi-Aventis Investigational Site Number 320703
  • Guatemala, Guatemala
    • Sanofi-Aventis Investigational Site Number 320704
• India
  • Bangalore, India, 560010
    • Sanofi-Aventis Investigational Site Number 356701
  • Bangalore, India, 560052
    • Sanofi-Aventis Investigational Site Number 356703
  • Hyderabad, India, 500001
    • Sanofi-Aventis Investigational Site Number 356702
  • Nagpur, India, 440012
    • Sanofi-Aventis Investigational Site Number 356704
• Mexico
  • Merida, Mexico, 97000
    • Sanofi-Aventis Investigational Site Number 484703
  • Tlalnepantla, Mexico, 53160
    • Sanofi-Aventis Investigational Site Number 484701
  • Zapopan, Mexico, 44030
    • Sanofi-Aventis Investigational Site Number 484704
• Peru
  • Lima, Peru, Lima 27
    • Sanofi-Aventis Investigational Site Number 604703
  • Lima, Peru, LIMA 31
    • Sanofi-Aventis Investigational Site Number 604701
  • Lima, Peru
    • Sanofi-Aventis Investigational Site Number 604702
  • Lima, Peru
    • Sanofi-Aventis Investigational Site Number 604705
• Puerto Rico
  • Carolina, Puerto Rico, 00983
    • Sanofi-Aventis Investigational Site Number 630714
  • Carolina, Puerto Rico, 00983
    • Sanofi-Aventis Investigational Site Number 630715
• Romania
  • Alba Iulia, Romania, 510 217
    • Sanofi-Aventis Investigational Site Number 642711
  • Bacau, Romania, 600164
    • Sanofi-Aventis Investigational Site Number 642702
  • Baia Mare, Romania, 430031
    • Sanofi-Aventis Investigational Site Number 642709
  • Brasov, Romania, 500326
    • Sanofi-Aventis Investigational Site Number 642701
  • Bucuresti, Romania, 010507
    • Sanofi-Aventis Investigational Site Number 642712
  • Bucuresti, Romania, 20475
    • Sanofi-Aventis Investigational Site Number 642714
  • Constanta, Romania, 900591
    • Sanofi-Aventis Investigational Site Number 642705
  • Galati, Romania, 800575
    • Sanofi-Aventis Investigational Site Number 642707
  • Ploiesti, Romania, 100097
    • Sanofi-Aventis Investigational Site Number 642703
  • Resita, Romania, 320076
    • Sanofi-Aventis Investigational Site Number 642713
  • Satu Mare, Romania, 440055
    • Sanofi-Aventis Investigational Site Number 642708
  • Targu Mures, Romania, 540061
    • Sanofi-Aventis Investigational Site Number 642706
  • Timisoara, Romania, 300456
    • Sanofi-Aventis Investigational Site Number 642715
  • Timisoara, Romania, 300593
    • Sanofi-Aventis Investigational Site Number 642710
• Turkey
  • Erzurum, Turkey
    • Sanofi-Aventis Investigational Site Number 792702
  • Istanbul, Turkey
    • Sanofi-Aventis Investigational Site Number 792705
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Sanofi-Aventis Investigational Site Number 840723
    • Birmingham, Alabama, United States, 35205
      • Sanofi-Aventis Investigational Site Number 840744
    • Birmingham, Alabama, United States, 35235
      • Sanofi-Aventis Investigational Site Number 840867
    • Birmingham, Alabama, United States, 35242
      • Sanofi-Aventis Investigational Site Number 840720
    • Mobile, Alabama, United States, 36608
      • Sanofi-Aventis Investigational Site Number 840855
    • Mobile, Alabama, United States, 36608
      • Sanofi-Aventis Investigational Site Number 840863
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Sanofi-Aventis Investigational Site Number 840775
    • Mesa, Arizona, United States, 85213
      • Sanofi-Aventis Investigational Site Number 840722
    • Phoenix, Arizona, United States, 85050
      • Sanofi-Aventis Investigational Site Number 840769
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
      • Sanofi-Aventis Investigational Site Number 840729
    • Mountain Home, Arkansas, United States, 72653
      • Sanofi-Aventis Investigational Site Number 840776
  • California
    • Artesia, California, United States, 90701
      • Sanofi-Aventis Investigational Site Number 840795
    • Chino, California, United States, 91710
      • Sanofi-Aventis Investigational Site Number 840782
    • Huntington Beach, California, United States, 92648
      • Sanofi-Aventis Investigational Site Number 840785
    • La Jolla, California, United States, 92037
      • Sanofi-Aventis Investigational Site Number 840858
    • Los Banos, California, United States, 93635
      • Sanofi-Aventis Investigational Site Number 840784
    • Mission Hills, California, United States, 91345
      • Sanofi-Aventis Investigational Site Number 840773
    • Mission Viejo, California, United States, 92691
      • Sanofi-Aventis Investigational Site Number 840707
    • Northridge, California, United States, 91325
      • Sanofi-Aventis Investigational Site Number 840733
    • Roseville, California, United States, 95661
      • Sanofi-Aventis Investigational Site Number 840864
    • San Diego, California, United States, 92123
      • Sanofi-Aventis Investigational Site Number 840772
    • San Mateo, California, United States, 94401
      • Sanofi-Aventis Investigational Site Number 840743
    • Stockton, California, United States, 95204
      • Sanofi-Aventis Investigational Site Number 840721
    • West Hills, California, United States, 91307
      • Sanofi-Aventis Investigational Site Number 840763
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Sanofi-Aventis Investigational Site Number 840872
    • Colorado Springs, Colorado, United States, 80909
      • Sanofi-Aventis Investigational Site Number 840868
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Sanofi-Aventis Investigational Site Number 840727
    • New Port Richey, Florida, United States, 34652
      • Sanofi-Aventis Investigational Site Number 840745
    • Oviedo, Florida, United States, 32765
      • Sanofi-Aventis Investigational Site Number 840761
    • Wellington, Florida, United States, 33414
      • Sanofi-Aventis Investigational Site Number 840799
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Sanofi-Aventis Investigational Site Number 840857
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Sanofi-Aventis Investigational Site Number 840724
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Sanofi-Aventis Investigational Site Number 840791
  • Indiana
    • Avon, Indiana, United States, 46123
      • Sanofi-Aventis Investigational Site Number 840738
    • Indianapolis, Indiana, United States, 46260
      • Sanofi-Aventis Investigational Site Number 840794
  • Kansas
    • Kansas City, Kansas, United States, 66160-7321
      • Sanofi-Aventis Investigational Site Number 840767
    • Lansing, Kansas, United States, 66043
      • Sanofi-Aventis Investigational Site Number 840779
    • Wichita, Kansas, United States, 67203
      • Sanofi-Aventis Investigational Site Number 840739
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Sanofi-Aventis Investigational Site Number 840789
    • Lexington, Kentucky, United States, 40504
      • Sanofi-Aventis Investigational Site Number 840850
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Sanofi-Aventis Investigational Site Number 840862
    • Shreveport, Louisiana, United States, 71101
      • Sanofi-Aventis Investigational Site Number 840879
  • Maryland
    • Hyattsville, Maryland, United States, 20783
      • Sanofi-Aventis Investigational Site Number 840764
    • Rockville, Maryland, United States, 20850
      • Sanofi-Aventis Investigational Site Number 840871
  • Massachusetts
    • Dartmouth, Massachusetts, United States, 2747
      • Sanofi-Aventis Investigational Site Number 840851
  • Michigan
    • Kalamazoo, Michigan, United States, 49001
      • Sanofi-Aventis Investigational Site Number 840708
  • Minnesota
    • Bloomington, Minnesota, United States, 55435
      • Sanofi-Aventis Investigational Site Number 840774
    • Eagan, Minnesota, United States, 55122
      • Sanofi-Aventis Investigational Site Number 840704
  • Mississippi
    • Picayune, Mississippi, United States, 39466
      • Sanofi-Aventis Investigational Site Number 840717
  • Missouri
    • St Louis, Missouri, United States, 63104
      • Sanofi-Aventis Investigational Site Number 840765
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Sanofi-Aventis Investigational Site Number 840875
    • Pahrump, Nevada, United States, 89048
      • Sanofi-Aventis Investigational Site Number 840866
  • New York
    • New York, New York, United States, 10010
      • Sanofi-Aventis Investigational Site Number 840865
    • New York City, New York, United States, 10021
      • Sanofi-Aventis Investigational Site Number 840766
    • Staten Island, New York, United States, 10301
      • Sanofi-Aventis Investigational Site Number 840874
    • West Seneca, New York, United States, 14224
      • Sanofi-Aventis Investigational Site Number 840762
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Sanofi-Aventis Investigational Site Number 840747
    • Greensboro, North Carolina, United States, 27401
      • Sanofi-Aventis Investigational Site Number 840760
    • High Point, North Carolina, United States, 27262
      • Sanofi-Aventis Investigational Site Number 840712
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanofi-Aventis Investigational Site Number 840780
    • Fargo, North Dakota, United States, 58103
      • Sanofi-Aventis Investigational Site Number 840877
  • Ohio
    • Athens, Ohio, United States, 45701
      • Sanofi-Aventis Investigational Site Number 840777
    • Cleveland, Ohio, United States, 44122
      • Sanofi-Aventis Investigational Site Number 840741
    • Dayton, Ohio, United States, 45458
      • Sanofi-Aventis Investigational Site Number 840728
    • Mentor, Ohio, United States, 44060
      • Sanofi-Aventis Investigational Site Number 840709
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Sanofi-Aventis Investigational Site Number 840716
  • Oregon
    • Medford, Oregon, United States, 97504
      • Sanofi-Aventis Investigational Site Number 840701
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Sanofi-Aventis Investigational Site Number 840751
    • Red Lion, Pennsylvania, United States, 17356
      • Sanofi-Aventis Investigational Site Number 840798
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Sanofi-Aventis Investigational Site Number 840792
    • Simpsonville, South Carolina, United States, 29681
      • Sanofi-Aventis Investigational Site Number 840740
    • Taylors, South Carolina, United States, 29687-4105
      • Sanofi-Aventis Investigational Site Number 840726
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Sanofi-Aventis Investigational Site Number 840711
  • Texas
    • Colleyville, Texas, United States, 76034
      • Sanofi-Aventis Investigational Site Number 840853
    • Houston, Texas, United States, 77030
      • Sanofi-Aventis Investigational Site Number 840730
    • San Antonio, Texas, United States, 78218
      • Sanofi-Aventis Investigational Site Number 840854
  • Utah
    • Clinton, Utah, United States, 84015
      • Sanofi-Aventis Investigational Site Number 840796
    • Salt Lake City, Utah, United States, 84102
      • Sanofi-Aventis Investigational Site Number 840755
    • Salt Lake City, Utah, United States, 84107
      • Sanofi-Aventis Investigational Site Number 840756
    • Salt Lake City, Utah, United States, 84107
      • Sanofi-Aventis Investigational Site Number 840758
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Sanofi-Aventis Investigational Site Number 840753
    • Norfolk, Virginia, United States, 23510
      • Sanofi-Aventis Investigational Site Number 840770
    • Richmond, Virginia, United States, 23220
      • Sanofi-Aventis Investigational Site Number 840752
    • Virginia Beach, Virginia, United States, 23502
      • Sanofi-Aventis Investigational Site Number 840757
  • Washington
    • Spokane, Washington, United States, 99209
      • Sanofi-Aventis Investigational Site Number 840735

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with pioglitazone

Exclusion Criteria:

• HbA1c less than (<) 7 percent (%) or greater than (>) 10% at screening
• At the time of screening age <legal age of majority
• Pregnant or breastfeeding women and women of childbearing potential without effective contraceptive method of birth control
• Type 1 diabetes mellitus
• Pioglitazone not at a stable dose of at least 30 milligram per day (mg/day) for at least 3 months prior to screening
• If treatment with metformin, no stable dose of at least 1.5 gram per day (g/day) 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])
• 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, or inflammatory bowel disease
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
• Hemoglobinopathy or hemolytic anemia, or receipt of blood or plasma products within3 months prior to the time of screening
• History of myocardial infarction or stroke within the last 6 months prior to screening
• 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 systolic blood pressure or diastolic blood pressure (DBP) >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
• Laboratory findings at the time of screening: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP): >2 times upper limit of normal (ULN) laboratory range; amylase and/or lipase: >3 times ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); Hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb); positive serum pregnancy test in females of childbearing potential
• Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram (ECG), 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 or constrains efficacy assessment
• Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements [such as scheduled visits, being able to do self-injections]; likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol)
• Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin or pioglitazone (for example, sulfonylurea, alpha-glucosidase inhibitor, other thiazolidinediones, rimonabant, exenatide, dipeptidyl peptidase-4 [DPP-4] inhibitors, insulin) 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
• Use of any investigational drug within 3 months prior to study
• Any previous treatment with lixisenatide or participation in a previous study with lixisenatide
• Renal impairment defined with creatinine >1.4 mg/dL in women and creatinine >1.5 mg/dL in men (applicable only for patients with metformin treatment)
• Patients with cardiac failure or history of cardiac failure (New York Heart Association class I to IV)
• End-stage renal disease defined by a serum creatinine clearance of <15 milliliter per minute (mL/min) (calculated by the Cockcroft and Gault formula) and/or patients on dialysis, if no treatment with metformin
• 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
• Allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past (for example,exenatide, liraglutide) or to metacresol
• Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (>2 injections missed); and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lixisenatide; 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.	Device: Pen auto-injector; Other Names: OptiClik®; Drug: Lixisenatide (AVE0010); Self-administered by subcutaneous injections once daily within the hour preceding breakfast.; Drug: Pioglitazone; Dose to be kept stable.; Drug: Metformin; Metformin, if given to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
PLACEBO_COMPARATOR: Placebo; 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.	Device: Pen auto-injector; Other Names: OptiClik®; Drug: Pioglitazone; Dose to be kept stable.; Drug: Metformin; Metformin, if given to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.; Drug: Placebo; Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day 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.	Baseline, Week 24
Change From Baseline in Body Weight at Week 24	Change was calculated by subtracting baseline value from Week 24 value. 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.	Baseline, Week 24
Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24	Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day 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.	Baseline, Week 24
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24	The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. 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.	Week 24
Percentage of Patients With HbA1c Level Less Than or Equal to 6.5% at Week 24	The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. 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.	Week 24
Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24	Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin [micro unit per milliliter]) divided by (fasting plasma glucose [mmol/L] minus 3.5). Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day 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.	Baseline, Week 24
Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period	Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG >270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8.5%. 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.	Baseline up to Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24	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.	Baseline, Week 24
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia	Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.	First dose of study drug up to 3 days after the last dose administration, for up to 132 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Guo H, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab. 2013 Nov;15(11):1000-7. doi: 10.1111/dom.12121. Epub 2013 May 26.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): June 1, 2011

Study Registration Dates

• First Submitted: September 30, 2008
• First Submitted That Met QC Criteria: September 30, 2008
• First Posted (ESTIMATE): October 1, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): November 28, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: hyperglycemia GLP-1 pioglitazone
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Pioglitazone; Lixisenatide
• Other Study ID Numbers: EFC6017; EudraCT: 2007-005884-92