Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin

NCT ID: NCT01169779

Last Updated: 2016-10-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 391 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2011-12-31

Brief Summary

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 with or without sulfonylurea, over a period of 24 weeks of treatment.

The primary objective is to assess the effects on glycemic control of lixisenatide (AVE0010) in comparison to placebo as an add-on treatment to metformin with or without sulfonylurea in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.

The secondary objectives are to assess the effects of lixisenatide over 24 weeks on percentage of patients reaching HbA1c less than (< ) 7 percent (%) or HbA1c less than or equal to (<=) 6.5%, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and glucose excursion during standardized meal test, body weight; to evaluate safety, tolerability, pharmacokinetic (PK) and anti-lixisenatide antibody development.

Detailed Description

The study duration for each patient is 27 weeks +/- 10 days (up to 2 weeks screening + 1 week run-in + 24 weeks double-blind treatment + 3 days follow-up).

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lixisenatide

1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24.

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

Metformin

Intervention Type: DRUG

Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.

Sulfonylurea

Intervention Type: DRUG

Sulfonylurea if given at screening, to be continued up to Week 24. In patients with a screening HbA1c \<8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values. In patients with a screening HbA1c \>=8%, the dose is not to be changed at randomization. In any case, after Week 12, sulfonylurea is to be continued at a stable dose.

Placebo

1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24.

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

Metformin

Intervention Type: DRUG

Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.

Sulfonylurea

Intervention Type: DRUG

Sulfonylurea if given at screening, to be continued up to Week 24. In patients with a screening HbA1c \<8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values. In patients with a screening HbA1c \>=8%, the dose is not to be changed at randomization. In any case, after Week 12, sulfonylurea is to be continued at a stable dose.

Interventions

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

Metformin

Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.

Intervention Type: DRUG

Sulfonylurea

Sulfonylurea if given at screening, to be continued up to Week 24. In patients with a screening HbA1c \<8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values. In patients with a screening HbA1c \>=8%, the dose is not to be changed at randomization. In any case, after Week 12, sulfonylurea is to be continued at a stable dose.

Intervention Type: DRUG

Other Intervention Names

OptiClik®

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin alone or metformin with sulfonylurea at the time of the screening visit

Exclusion Criteria

• HbA1c <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 metformin not at a stable dose of at least 1.0 gram per day or more than 1.5 gram per day for at least 3 months prior to screening visit
• In case of treatment with sulfonylurea, if the sulfonylurea dosage is less than the maximum effective dose (that is, half of the maximum recommended dose according to local labeling), or is not at a stable (unchanged) dose for at least 3 months prior to screening
• FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
• History of hypoglycemia unawareness
• Body mass index <=20 kilogram per square meter (kg/m^2)
• Weight change of >5 kg during the 3 months preceding the screening visit
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, or inflammatory bowel disease or patients considered by the investigator at high risk for acute pancreatitis (for example, with known history of biliary gallstone[s], or with very high triglyceride level [>=5.65 mmol/L]) at the time of screening
• Personal or family history of medullary thyroid cancer or genetic conditions that predispose to medullary thyroid cancer (for example, multiple endocrine neoplasia syndromes);
• 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 systolic blood pressure (SBP) or diastolic blood pressure (DBP) >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
• Laboratory findings at the time of screening: amylase and/or lipase: >3 times upper limit of normal (ULN); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; calcitonin >20 picogram per milliliter (5.9 picomole per liter) ; and positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
• Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram, 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 attending 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 and sulfonylurea (for example, alpha-glucosidase inhibitor, thiazolidinedione, glucagon-like peptide -1 [GLP-1], receptor agonist, dipeptidyl-peptidase-4 inhibitors, insulin) within 3 months prior to the time of screening
• 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
• 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, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
• Allergic reaction to any GLP-1 agonist in the past (for example, exenatide, liraglutide) or to metacresol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 156011

Beijing, , China

Investigational Site Number 156012

Beijing, , China

Investigational Site Number 156019

Beijing, , China

Investigational Site Number 156002

Beijing, , China

Investigational Site Number 156003

Beijing, , China

Investigational Site Number 156009

Beijing, , China

Investigational Site Number 156001

Beijing, , China

Investigational Site Number 156036

Changchun, , China

Investigational Site Number 156016

Changsha, , China

Investigational Site Number 156015

Changsha, , China

Investigational Site Number 156006

Chengdu, , China

Investigational Site Number 156032

Chengdu, , China

Investigational Site Number 156010

Dalian, , China

Investigational Site Number 156004

Guangzhou, , China

Investigational Site Number 156008

Guangzhou, , China

Investigational Site Number 156025

Guangzhou, , China

Investigational Site Number 156031

Haikou, , China

Investigational Site Number 156014

Harbin, , China

Investigational Site Number 156029

Hefei, , China

Investigational Site Number 156013

Qingdao, , China

Investigational Site Number 156007

Shanghai, , China

Investigational Site Number 156030

Shanghai, , China

Investigational Site Number 156020

Shenyang, , China

Investigational Site Number 156035

Suzhou, , China

Investigational Site Number 156033

Taiyuan, , China

Investigational Site Number 156037

Tianjin, , China

Investigational Site Number 156022

Xi'an, , China

Investigational Site Number 156023

Xi'an, , China

Investigational Site Number 344001

Hong Kong, , Hong Kong

Investigational Site Number 344003

Hong Kong, , Hong Kong

Investigational Site Number 344002

Shatin, Nt, , Hong Kong

Investigational Site Number 458001

Kelantan, , Malaysia

Investigational Site Number 458003

Kuala Lumpur, , Malaysia

Investigational Site Number 458002

Putrajaya, , Malaysia

Investigational Site Number 764002

Bangkok, , Thailand

Countries

China; Hong Kong; Malaysia; Thailand

References

Yu Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, Lv X, Tian H, Jin Kui Y, Su B, Shang S, Niemoeller E. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). Diabetes Metab Res Rev. 2014 Nov;30(8):726-35. doi: 10.1002/dmrr.2541.

Reference Type: RESULT

PMID: 24639432 (View on PubMed)

Seino H, Onishi Y, Naito Y, Komatsu M. Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. Diabetol Metab Syndr. 2016 Jun 1;8:36. doi: 10.1186/s13098-016-0151-7. eCollection 2016.

Reference Type: DERIVED

PMID: 27252787 (View on PubMed)

Other Identifiers

U1111-1116-8938

Identifier Type: OTHER

Identifier Source: secondary_id

EFC11321

Identifier Type: -

Identifier Source: org_study_id