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

A Randomized, Open Label, Parallel-group (One-step Titration and Two-step Titration), Multicenter 52-Week Study Followed by a 24-Week Extension Assessing the Safety and Tolerability of AVE0010 Monotherapy in Patients With Type 2 Diabetes

The purpose of this study is to compare the benefits and risks of lixisenatide (AVE0010) used as 2-step initiation regimen and 1-step initiation regimen in Japan, over a period of 24 weeks of treatment, followed by an extension up to Week 76.

The primary objective of this study is to evaluate the safety of lixisenatide once daily treatment in monotherapy at Week 24 by a descriptive comparison of a 1-step initiation and a 2-step initiation regimen in patients with type 2 diabetes in Japan.

The secondary objectives are to assess the overall safety of lixisenatide once daily treatment in monotherapy at Week 52 and Week 76; to assess the effects of lixisenatide on glycosylated hemoglobin (HbA1c) reduction at Week 52 and Week 76, body weight, and fasting plasma glucose (FPG); to assess pharmacokinetics (PK) and anti-lixisenatide antibody development.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 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 2 months at the time of screening visit, not treated by an antidiabetic agent in the 3 months before screening, except treatment with sulfonylureas or alpha-glucosidase inhibitors at a stable dose. In this case the oral antidiabetic treatment must be discontinued before starting single-blind run-in phase

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 or women of childbearing potential with no effective contraceptive method
• Type 1 diabetes mellitus
• Type 2 diabetes treated by an antidiabetic pharmacological agent (except sulfonylurea or alpha-glucosidase inhibitors at a stable dose) within the 3 months preceding the screening. Insulin use is accepted if it is not within 3 months prior to screening visit and only for the following reasons: a) Prior insulin use for management of gestational diabetes; b) Short-term (less than or equal to [<=] 1 month) insulin use to maintain glycemic control for hospitalization, medical procedures, or intervention
• FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
• Weight change of more than 5 kilogram (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)
• Patient is an investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol
• 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 screening
• Participation in a previous study with lixisenatide
• End-stage renal disease as defined by a serum creatinine clearance of <15 milliliter/minute (calculated by the Cockcroft and Gault formula) 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 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 (patient not willing to continue or failed to return); 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 Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 end of treatment.	Drug: Lixisenatide (AVE0010); Self administered by subcutaneous injections once daily within the hour preceding breakfast.; Device: Pen auto-injector; Other Names: OptiClik®
Experimental: Lixisenatide (One-step Titration); 1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to end of treatment.	Drug: Lixisenatide (AVE0010); Self administered by subcutaneous injections once daily within the hour preceding breakfast.; Device: Pen auto-injector; Other Names: OptiClik®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of the One-Step and Two-Step Titration Arms Assessed Through Adverse Events Collection and Vital Signs, Electrocardiogram (ECG) and Laboratory Monitoring	Overview of adverse event profile is reported in terms of percentage of patients with treatment emergent adverse events (TEAEs) during the 24-week treatment period: any TEAE; any serious TEAE; any TEAE leading to death; and any TEAE leading to permanent treatment discontinuation.	First dose of study drug up to 3 days after the last dose of study drug at Week 24 or early withdrawal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of All Patients During On-Treatment Period Assessed Through Adverse Events Collection and Vital Signs, ECG and Laboratory Monitoring	Overview of adverse event profile is reported in terms of percentage of patients with TEAEs during the on-treatment period: any TEAE; any serious TEAE; any TEAE leading to death; any TEAE leading to permanent treatment discontinuation. The on-treatment period was the time from the first dose of study drug up to 3 days after the last dose at Week 76.	First dose of study drug up to 3 days after the last dose of study drug at Week 76 or early withdrawal
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) for All Patients at Week 52 and 76	Absolute change = HbA1c value at week of assessment (Week 52/Week 76) 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 mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.	Baseline, Week 52, 76
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 52 and 76	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 52, 76
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 52 and 76	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 52, 76
Change From Baseline in Body Weight for All Patients at Week 52 and 76	Change was calculated by subtracting baseline value from value at week of assessment (Week 52/Week 76). 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.	Baseline, Week 52, 76
Change From Baseline in Fasting Plasma Glucose (FPG) for All Patients at Week 52 and 76	Change was calculated by subtracting baseline value from value at week of assessment (Week 52/Week 76). 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.	Baseline, Week 52, 76

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Requiring Rescue Therapy	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 Week 4 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%, from Week 24 to end of treatment (Week 76): fasting SMPG/FPG >180 mg/dL (10.0 mmol/L) or HbA1c >8%. 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 52, Baseline up to Week 76
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for the One-Step and Two-Step Titration Arms During 24-Week Treatment Period	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 less than 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 of study drug at Week 24 or early withdrawal
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for All Patients During On-Treatment Period	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 less than 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.The on-treatment period was the time from the first dose of study drug up to 3 days after the last dose.	First dose of study drug up to 3 days after the last dose of study drug at Week 76 or early withdrawal

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Seino Y, Yabe D, Takami A, Niemoeller E, Takagi H. Long-term safety of once-daily lixisenatide in Japanese patients with type 2 diabetes mellitus: GetGoal-Mono-Japan. J Diabetes Complications. 2015 Nov-Dec;29(8):1304-9. doi: 10.1016/j.jdiacomp.2015.07.003. Epub 2015 Jul 6.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: May 14, 2009
• First Submitted That Met QC Criteria: May 18, 2009
• First Posted (Estimate): May 20, 2009

Study Record Updates

• Last Update Posted (Estimate): December 21, 2016
• Last Update Submitted That Met QC Criteria: October 28, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: GLP-1; hyperglycemia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Lixisenatide
• Other Study ID Numbers: LTS10888