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

NCT ID: NCT00688701

Last Updated: 2016-12-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

361 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2009-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diabetes Mellitus, Type 2

Keywords

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hyperglycemia, GLP-1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Pen auto-injector

Intervention Type DEVICE

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Pen auto-injector

Intervention Type DEVICE

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.

Group Type EXPERIMENTAL

Lixisenatide (AVE0010)

Intervention Type DRUG

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Pen auto-injector

Intervention Type DEVICE

Lixisenatide (One-Step Titration)

1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to Week 12.

Group Type EXPERIMENTAL

Lixisenatide (AVE0010)

Intervention Type DRUG

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Pen auto-injector

Intervention Type DEVICE

Interventions

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Lixisenatide (AVE0010)

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Intervention Type DRUG

Placebo

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Intervention Type DRUG

Pen auto-injector

Intervention Type DEVICE

Other Intervention Names

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OptiClik®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Site Status

Sanofi-Aventis Administrative Office

Diegem, , Belgium

Site Status

Sanofi-Aventis Administrative Office

Mumbai, , India

Site Status

Sanofi-Aventis Administrative Office

Netanya, , Israel

Site Status

Sanofi-Aventis Administrative Office

Tokyo, , Japan

Site Status

Sanofi-Aventis Administrative Office

México, , Mexico

Site Status

Sanofi-Aventis Administrative Office

Warsaw, , Poland

Site Status

Sanofi-Aventis Administrative Office

Bucharest, , Romania

Site Status

Sanofi-Aventis Administrative Office

Moscow, , Russia

Site Status

Sanofi-Aventis Administrative Office

Seoul, , South Korea

Site Status

Sanofi-Aventis Administrative Office

Mégrine, , Tunisia

Site Status

Sanofi-Aventis Administrative Office

Kiev, , Ukraine

Site Status

Countries

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United States Belgium India Israel Japan Mexico Poland Romania Russia South Korea Tunisia Ukraine

References

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Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE; EFC6018 GetGoal-Mono Study Investigators. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012 Jun;35(6):1225-31. doi: 10.2337/dc11-1935. Epub 2012 Mar 19.

Reference Type RESULT
PMID: 22432104 (View on PubMed)

Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

Reference Type DERIVED
PMID: 38770818 (View on PubMed)

Other Identifiers

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EudraCT 2007-005887-29

Identifier Type: -

Identifier Source: secondary_id

EFC6018

Identifier Type: -

Identifier Source: org_study_id