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GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin (GETGOAL-F1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00763451
First received: September 30, 2008
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Lixisenatide (AVE0010)
Drug: Placebo
Device: Pen auto-injector
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 in Two Titration Regimens on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Body Weight at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
    Routine fasting self-measured 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.


Other Outcome Measures:
  • Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia [ Time Frame: First dose of study drug up to 3 days after the last dose administration ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 484
Study Start Date: September 2008
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lixisenatide (Two-Step Titration)
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)
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®
Drug: Metformin
Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
Experimental: Lixisenatide (One-Step Titration)
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)
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®
Drug: Metformin
Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
Placebo Comparator: Placebo (Two-Step Titration)
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: Placebo
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®
Drug: Metformin
Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
Placebo Comparator: Placebo (One-Step Titration)
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: Placebo
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®
Drug: Metformin
Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.

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 scheduled date of Week 76 visit (Visit 25) for the last randomized patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Laboratory findings at the time of screening: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP): >2 times upper limit of the 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 <100000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb) and 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 oral or injectable antidiabetic or hypoglycemic agents other than metformin (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, rimonabant, exenatide, dipeptidylpeptidase-4 [DPP-IV] inhibitor, insulin) within 3 months prior to the time of screening
  • Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one 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 any 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00763451

Locations
United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Brazil
Sanofi-Aventis Administrative Office
Sao Paulo, Brazil
Chile
Sanofi-Aventis Administrative Office
Santiago, Chile
Colombia
Sanofi-Aventis Administrative Office
Santafe de Bogota, Colombia
Estonia
Sanofi-Aventis Administrative Office
Tallinn, Estonia
Germany
Sanofi-Aventis Administrative Office
Berlin, Germany
Italy
Sanofi-Aventis Administrative Office
Milano, Italy
Lithuania
Sanofi-Aventis Administrative Office
Vilnius, Lithuania
Malaysia
Sanofi-Aventis Administrative Office
Kuala Lumpur, Malaysia
Mexico
Sanofi-Aventis Administrative Office
Mexico, Mexico
Philippines
Sanofi-Aventis Administrative Office
Makati City, Philippines
Poland
Sanofi-Aventis Administrative Office
Warszawa, Poland
Romania
Sanofi-Aventis Administrative Office
Bucuresti, Romania
Slovakia
Sanofi-Aventis Administrative Office
Brastislava, Slovakia
Ukraine
Sanofi-Aventis Administrative Office
Kiev, Ukraine
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00763451     History of Changes
Other Study ID Numbers: EFC10743, 2008-001002-16
Study First Received: September 30, 2008
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
hyperglycemia, GLP-1

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 24, 2014