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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00712673




Registration number
NCT00712673
Ethics application status
Date submitted
7/07/2008
Date registered
10/07/2008
Date last updated
15/12/2016

Titles & IDs
Public title
GLP-1 Receptor Agonist Lixisenatide (Morning or Evening) in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin
Scientific title
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin
Secondary ID [1] 0 0
EudraCT 2007-005880-80
Secondary ID [2] 0 0
EFC6014
Universal Trial Number (UTN)
Trial acronym
GETGOAL-M
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lixisenatide (AVE0010)
Treatment: Drugs - Placebo
Treatment: Devices - Pen auto-injector
Treatment: Drugs - Metformin

Experimental: Lixisenatide (Morning Injection) - 2-step initiation morning 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 end of treatment.

Experimental: Lixisenatide (Evening Injection) - 2-step initiation evening regimen of lixisenatide: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.

Placebo Comparator: Placebo (Morning Injection) - 2-step initiation morning 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 end of treatment.

Placebo Comparator: Placebo (Evening Injection) - 2-step initiation evening 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 end of treatment.


Treatment: Drugs: Lixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding meal (either breakfast or dinner).

Treatment: Drugs: Placebo
Self administered by subcutaneous injections once daily within the hour preceding meal (either breakfast or dinner).

Treatment: Devices: Pen auto-injector


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

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24 - The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the 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.
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) 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 the last dosing day of the 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.
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Change From Baseline in Fasting Proinsulin 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 last dosing day 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.
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Change From Baseline in 2-Hour Postprandial Proinsulin 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 last dosing day 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.
Timepoint [7] 0 0
Baseline, Week 24
Secondary outcome [8] 0 0
Change From Baseline in Fasting C-Peptide 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 last dosing day 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.
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Change From Baseline in 2-Hour Postprandial C-Peptide 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 last dosing day 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.
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
Change From Baseline in Fasting Glucagon 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 last dosing day 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.
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Change From Baseline in 2-Hour Postprandial Glucagon 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 last dosing day 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.
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
Change From Baseline in Adiponectin 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.
Timepoint [12] 0 0
Baseline, Week 24
Secondary outcome [13] 0 0
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 (FPG [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 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.
Timepoint [13] 0 0
Baseline, Week 24
Secondary outcome [14] 0 0
Percentage of Patients Requiring Rescue Therapy During the 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.
Timepoint [14] 0 0
Baseline up to Week 24
Secondary outcome [15] 0 0
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% 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.
Timepoint [15] 0 0
Week 24
Secondary outcome [16] 0 0
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% 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.
Timepoint [16] 0 0
Week 24

Eligibility
Key inclusion criteria
- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit,
insufficiently controlled with metformin at a stable dose of at least 1.5 gram/ day
(g/day) for at least 3 months prior to screening visit
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- HbA1c <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 (BMI) <=20 kilogram per square meter (kg/m^2)

- Weight change of >5 kg during the 3 months preceding the study 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 blood pressure or diastolic blood pressure >180 millimeter of
mercury (mmHg) or >95 mmHg, respectively

- Laboratory findings at the time of screening: aspartate aminotransferase, alanine
aminotransferase, or alkaline phosphatase: >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 and/or Hepatitis C antibody; positive serum
pregnancy test in females of child bearing potential

- Any clinically significant abnormality identified on physical examination, laboratory
tests, electrocardiogram, 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 (for example, sulfonylurea, alpha glucosidase inhibitor, other
thiazolidinediones, rimonabant, exenatide, dipeptidyl-peptidase-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

- 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
sanofi-aventis Australia & New Zealand administrative office - Macquarie Park
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Canada
State/province [2] 0 0
Laval
Country [3] 0 0
Chile
State/province [3] 0 0
Santiago
Country [4] 0 0
Croatia
State/province [4] 0 0
Zagreb
Country [5] 0 0
Czech Republic
State/province [5] 0 0
Praha
Country [6] 0 0
Germany
State/province [6] 0 0
Berlin
Country [7] 0 0
Mexico
State/province [7] 0 0
Mexico
Country [8] 0 0
Morocco
State/province [8] 0 0
Casablanca
Country [9] 0 0
Philippines
State/province [9] 0 0
Makati City
Country [10] 0 0
Romania
State/province [10] 0 0
Bucuresti
Country [11] 0 0
Russian Federation
State/province [11] 0 0
Moscow
Country [12] 0 0
South Africa
State/province [12] 0 0
Midrand
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Ukraine
State/province [14] 0 0
Kiev
Country [15] 0 0
Venezuela
State/province [15] 0 0
Caracas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
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 as an add-on treatment to
metformin in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.

The secondary objectives are to assess the effect of lixisenatide, in comparison to placebo,
when administered in the evening within 1 hour prior to the meal in terms of HbA1c reduction,
percentage of patients reaching HbA1c less than (<) 7 percent (%), percentage of patients
reaching HbA1c less than or equal to 6.5%, fasting plasma glucose (FPG), plasma glucose,
plasma insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test
(only in morning injection arms), body weight, beta-cell function assessed by homeostasis
model assessment (HOMA)-beta, fasting plasma insulin (FPI) and adiponectin; to evaluate
safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development,
beta-cell function 4 weeks after study drug discontinuation (only in patients from the
morning injection arms in some selected centers).
Trial website
https://clinicaltrials.gov/show/NCT00712673
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications