GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy (GETGOAL-MONO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00688701
First received: May 7, 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, used in a 2-step dose titration regimen in monotherapy, over a period of 12 weeks of treatment.

The primary objective is to assess the effects of lixisenatide, in comparison to placebo, on glycemic control using a 2-step dose titration regimen in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 12.

Secondary objectives are to assess the effects of lixisenatide, in comparison to placebo, on glycemic control in terms of HbA1c reduction when it is used in a one-step dose titration regimen over a period of 12 weeks, body weight, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) after a standardized meal, to assess the safety and tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter 12-week Study Assessing the Efficacy and Safety of AVE0010 in Patients With Type 2 Diabetes Not Treated With Antidiabetic Agents

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 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Absolute change = HbA1c value at Week 12 minus HbA1c value at baseline. 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 modified intent-to-treat (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 2-Hour Postprandial Plasma Glucose (PPG) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal (performed in selected sites). Change was calculated by subtracting baseline value from Week 12 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.

  • Change From Baseline in Body Weight at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Change was calculated by subtracting baseline value from Week 12 value. 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.

  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Change was calculated by subtracting baseline value from Week 12 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day 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.

  • Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: No ]
    Routine fasting self monitored plasma glucose (SMPG) and central laboratory FPG 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 was performed. Threshold values for fasting SMPG/FPG: from baseline to Week 8: >270 milligram/deciliter (mg/dL) (15 mmol/L) and from Week 8 to Week 12: >240 mg/dL (13.3 mmol/L). 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:
  • Change From Baseline in Glucose Excursion at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test (performed in selected sites), before study drug administration. Change was calculated by subtracting baseline value from Week 12 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.

  • Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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: 361
Study Start Date: May 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo (Two-Step Titration)
2-step initiation regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 12.
Drug: Placebo
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®
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 Week 12.
Drug: Placebo
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®
Experimental: Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 12.
Drug: Lixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®
Experimental: Lixisenatide (One-Step Titration)
1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to Week 12.
Drug: Lixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
Device: Pen auto-injector
Other Name: OptiClik®

Detailed Description:

This is a double-blind, randomized, placebo-controlled, 4-arm, unbalanced design, parallel group study with a two-step titration regimen or a one-step titration regimen. The study is double-blind with regard to active and placebo treatments; however neither the study drug volume nor the titration regimens (that is, two-step or one-step) are blinded.

  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 2 months at the time of the screening visit, not treated with any antidiabetic agent

Exclusion Criteria:

  • HbA1c less than (<) 7 percent (%) or greater than (>) 10%
  • 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
  • Type 2 diabetes treated by an antidiabetic agent within the 3 months preceding the study
  • Fasting plasma glucose 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 previous 3 months
  • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
  • History of metabolic acidosis, including diabetic ketoacidosis within the previous year
  • Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within the previous 3 months
  • History of myocardial infarction, stroke, or heart failure requiring hospitalization within the previous 6 months
  • Known history of drug or alcohol abuse within the previous 6 months
  • 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 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, alanine aminotransferase or alkaline phosphatase: >2 times the upper limit of the normal (ULN) laboratory range; amylase and/or lipase: >3 ULN; total bilirubin: >1.5 ULN (except in case of Gilbert's syndrome); hemoglobin <11 gram/deciliter (g/dL) and/or neutrophils <1,500 per cubic mm (mm^3) and/or platelets <100,000/mm^3; positive test for Hepatitis B surface antigen and/or hepatitis C antibody
  • Any clinically significant abnormality identified by physical examination, laboratory tests, electrocardiogram or vital sign at the time of screening that in the judgment of the investigator or any sub investigator precludes safe completion of the study or hinders the efficacy assessment
  • Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason
  • Use of systemic glucocorticoids (excluding topical application or inhaled forms) within the previous 3 months
  • Participation in any previous study with lixisenatide
  • Use of any investigational drug within 3 months prior to study
  • End-stage renal disease as defined by a calculated serum creatinine clearance of <15 milliliter/minute and/or patients on dialysis
  • 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 the previous 6 months
  • History of allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past 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: more than 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: NCT00688701

Locations
United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Belgium
Sanofi-Aventis Administrative Office
Diegem, Belgium
India
Sanofi-Aventis Administrative Office
Mumbai, India
Israel
Sanofi-Aventis Administrative Office
Natanya, Israel
Japan
Sanofi-Aventis Administrative Office
Tokyo, Japan
Korea, Republic of
Sanofi-Aventis Administrative Office
Seoul, Korea, Republic of
Mexico
Sanofi-Aventis Administrative Office
Mexico, Mexico
Poland
Sanofi-Aventis Administrative Office
Warszawa, Poland
Romania
Sanofi-Aventis Administrative Office
Bucuresti, Romania
Russian Federation
Sanofi-Aventis Administrative Office
Moscow, Russian Federation
Tunisia
Sanofi-Aventis Administrative Office
Megrine, Tunisia
Ukraine
Sanofi-Aventis Administrative Office
Kiev, Ukraine
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00688701     History of Changes
Other Study ID Numbers: EFC6018, EudraCT 2007-005887-29
Study First Received: May 7, 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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014