Clinical trial NCT00905255: GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy (GETGOAL-MONO Japan LTS)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: hyperglycemia
GLP-1
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-05-20
Enrollment: 69
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: First dose of study drug up to 3 days after the last dose of study drug at Week 24 or early withdrawal
Secondary outcomes:
measure: 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
timeFrame: First dose of study drug up to 3 days after the last dose of study drug at Week 76 or early withdrawal
measure: Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) for All Patients at Week 52 and 76
timeFrame: Baseline, Week 52, 76
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 52 and 76
timeFrame: Week 52, 76
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 52 and 76
timeFrame: Week 52, 76
measure: Change From Baseline in Body Weight for All Patients at Week 52 and 76
timeFrame: Baseline, Week 52, 76
measure: Change From Baseline in Fasting Plasma Glucose (FPG) for All Patients at Week 52 and 76
timeFrame: Baseline, Week 52, 76
Other outcomes:
measure: Percentage of Patients Requiring Rescue Therapy
timeFrame: Baseline up to Week 52, Baseline up to Week 76
measure: Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for the One-Step and Two-Step Titration Arms During 24-Week Treatment Period
timeFrame: First dose of study drug up to 3 days after the last dose of study drug at Week 24 or early withdrawal
measure: Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for All Patients During On-Treatment Period
timeFrame: First dose of study drug up to 3 days after the last dose of study drug at Week 76 or early withdrawal
Locations:
city: Tokyo
country: Japan
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.