24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine

NCT ID: NCT00975286

Last Updated: 2016-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 446 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2011-08-31

Brief Summary

The purpose of the study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to insulin glargine and metformin with or without thiazolidinediones (TZDs), over a period of 24 weeks of treatment.

The primary objective is to assess the effects of lixisenatide in comparison to placebo, when added to insulin glargine and metformin, on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.

The secondary objectives are to assess the effects of lixisenatide on the percentage of patients reaching HbA1c less than (<) 7 percent (%) and less than or equal to (<=) 6.5%, plasma glucose (fasting, postprandial during a standardized meal challenge test, 7-point self monitored profiles), body weight, insulin glargine doses, to evaluate safety and tolerability (including anti-lixisenatide antibody assessment), and to assess the impact on treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (state) (DTSQs) in the participating countries where it is validated.

Detailed Description

The study comprises 3 periods:

• An up to 14-week screening period, which includes an up to 2-week screening phase and a 12-week run-in phase with introduction and titration of insulin glargine on top of metformin +/-TZDs.
• At the end of the run-in phase, patients whose HbA1c (centralized assay) is greater than or equal to (>=) 7% and less than or equal to (<=) 9% and whose mean fasting self-monitored plasma glucose (SMPG) calculated from the self measurements for the 7 days prior to Visit 12 (Week -1) is <=140 milligram per deciliter (mg/dL) (7.8 millimole per liter [mmol/L]), would enter a 24-week double-blind randomized treatment period comparing lixisenatide to placebo (on top of insulin glargine + metformin +/- TZDs).
• A 3-day safety follow up period.

Maximum duration is of 39 weeks +/- 7 days.

Conditions

Type 2 Diabetes Mellitus

Study Design

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

Study Groups

Lixisenatide

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 Week 24.

Group Type: EXPERIMENTAL

Lixisenatide (AVE0010)

Intervention Type: DRUG

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

Insulin glargine

Intervention Type: DRUG

Dose to be adjusted to maintain a fasting SMPG between 100 and 80 mg/dL (5.6 and 4.4 mmol/L), inclusive.

Pen auto-injector

Intervention Type: DEVICE

Lantus® SoloStar® OptiClik®

Metformin

Intervention Type: DRUG

Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.

Thiazolidinedione (TZD)

Intervention Type: DRUG

TZD (either rosiglitazone or pioglitazone) if given, to be continued at stable dose up to Week 24.

Placebo

2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 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.

Insulin glargine

Intervention Type: DRUG

Dose to be adjusted to maintain a fasting SMPG between 100 and 80 mg/dL (5.6 and 4.4 mmol/L), inclusive.

Pen auto-injector

Intervention Type: DEVICE

Lantus® SoloStar® OptiClik®

Metformin

Intervention Type: DRUG

Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.

Thiazolidinedione (TZD)

Intervention Type: DRUG

TZD (either rosiglitazone or pioglitazone) if given, to be continued at stable dose up to Week 24.

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

Insulin glargine

Dose to be adjusted to maintain a fasting SMPG between 100 and 80 mg/dL (5.6 and 4.4 mmol/L), inclusive.

Intervention Type: DRUG

Pen auto-injector

Lantus® SoloStar® OptiClik®

Intervention Type: DEVICE

Metformin

Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.

Intervention Type: DRUG

Thiazolidinedione (TZD)

TZD (either rosiglitazone or pioglitazone) if given, to be continued at stable dose up to Week 24.

Intervention Type: DRUG

Other Intervention Names

Lantus®

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with insulin glargine and metformin

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
• Metformin not at a stable dose of at least 1.5 gram per day for at least 3 months prior to the screening visit
• Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin, sulfonylurea (SU) and TZDs (for example, alpha glucosidase inhibitor, other glucagon like peptide-1 [GLP-1] receptor agonists, dipeptidyl peptidase-IV [DPP-IV] inhibitors, insulin etc.) within 3 months prior to the time of screening, use of weight loss drugs if not at a stable dose for at least 3 months prior to the screening visit
• History of hypoglycemia unawareness
• Body Mass Index (BMI) less than or equal to (<=) 20 kilogram per square meter (kg/m^2)
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for example, multiple endocrine neoplasia syndromes)
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
• Hemoglobinopathy or hemolytic anemia, blood or plasma products transfusion 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
• 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 such as active malignant tumor or other major systemic diseases, presence of clinically significant diabetic retinopathy 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 or diastolic blood pressure >180 millimeter of mercury (mmHg) or >110 mmHg, respectively
• Laboratory findings at the time of screening: amylase and/or lipase, alanine aminotransferase >3 times upper limit of the normal (ULN) laboratory range; 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 <100 000/mm^3; positive test for Hepatitis B surface antigen and/or Hepatitis C antibody, positive serum pregnancy test in females of childbearing potential; and calcitonin >=20 picogram per milliliter (pg/mL) (5.9 picomole per milliliter [pmol/L])
• 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 being investigator or any sub investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol etc.)
• Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening
• Use of any investigational drug within 3 months prior to screening
• Renal impairment defined with serum creatinine > 1.4 mg/dL in women and > 1.5 mg/dL in men
• History of hypersensitivity to insulin glargine or to any of the excipients
• 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
• Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide)
• Allergic reaction to any GLP-1 receptor 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 Study Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Investigational Site Number 840223

Mesa, Arizona, United States

Sanofi-Aventis Investigational Site Number 840206

Hot Springs, Arkansas, United States

Sanofi-Aventis Investigational Site Number 840201

Little Rock, Arkansas, United States

Sanofi-Aventis Investigational Site Number 840212

Mountain Home, Arkansas, United States

Sanofi-Aventis Investigational Site Number 840215

Concord, California, United States

Sanofi-Aventis Investigational Site Number 840214

Greenbrae, California, United States

Sanofi-Aventis Investigational Site Number 840221

Orlando, Florida, United States

Sanofi-Aventis Investigational Site Number 840211

Baton Rouge, Louisiana, United States

Sanofi-Aventis Investigational Site Number 840230

Hyattsville, Maryland, United States

Sanofi-Aventis Investigational Site Number 840209

Rockville, Maryland, United States

Sanofi-Aventis Investigational Site Number 840219

Brighton, Michigan, United States

Sanofi-Aventis Investigational Site Number 840231

Sea Girt, New Jersey, United States

Sanofi-Aventis Investigational Site Number 840208

Fargo, North Dakota, United States

Sanofi-Aventis Investigational Site Number 840225

Mentor, Ohio, United States

Sanofi-Aventis Investigational Site Number 840222

Portland, Oregon, United States

Sanofi-Aventis Investigational Site Number 840202

Philadelphia, Pennsylvania, United States

Sanofi-Aventis Investigational Site Number 840229

Bristol, Tennessee, United States

Sanofi-Aventis Investigational Site Number 840205

Germantown, Tennessee, United States

Sanofi-Aventis Investigational Site Number 840210

Dallas, Texas, United States

Sanofi-Aventis Investigational Site Number 840217

Houston, Texas, United States

Sanofi-Aventis Investigational Site Number 840228

Houston, Texas, United States

Sanofi-Aventis Investigational Site Number 840213

Plano, Texas, United States

Sanofi-Aventis Investigational Site Number 840227

Norfolk, Virginia, United States

Sanofi-Aventis Investigational Site Number 032204

Buenos Aires, , Argentina

Sanofi-Aventis Investigational Site Number 032205

Capital Federal, , Argentina

Sanofi-Aventis Investigational Site Number 032201

Capital Federal, , Argentina

Sanofi-Aventis Investigational Site Number 032209

Capital Federal, , Argentina

Sanofi-Aventis Investigational Site Number 032211

Corrientes, , Argentina

Sanofi-Aventis Investigational Site Number 032202

Paraná, , Argentina

Sanofi-Aventis Investigational Site Number 032203

Rosario, , Argentina

Sanofi-Aventis Investigational Site Number 076207

Belém, , Brazil

Sanofi-Aventis Investigational Site Number 076202

Brasília, , Brazil

Sanofi-Aventis Investigational Site Number 076205

Porto Alegre, , Brazil

Sanofi-Aventis Investigational Site Number 076204

São Paulo, , Brazil

Sanofi-Aventis Investigational Site Number 124219

Brampton, , Canada

Sanofi-Aventis Investigational Site Number 124213

Chatham, , Canada

Sanofi-Aventis Investigational Site Number 124208

Chilliwack, , Canada

Sanofi-Aventis Investigational Site Number 124215

Etobicoke, , Canada

Sanofi-Aventis Investigational Site Number 124205

Québec, , Canada

Sanofi-Aventis Investigational Site Number 124202

Red Deer, , Canada

Sanofi-Aventis Investigational Site Number 124218

Thornhill, , Canada

Sanofi-Aventis Investigational Site Number 124201

Toronto, , Canada

Sanofi-Aventis Investigational Site Number 124207

Toronto, , Canada

Sanofi-Aventis Investigational Site Number 124209

Victoria, , Canada

Sanofi-Aventis Investigational Site Number 124217

Winnipeg, , Canada

Sanofi-Aventis Investigational Site Number 152202

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152203

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152206

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152204

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152205

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 152201

Santiago, , Chile

Sanofi-Aventis Investigational Site Number 170204

Barranquilla, , Colombia

Sanofi-Aventis Investigational Site Number 170201

Bogotá, , Colombia

Sanofi-Aventis Investigational Site Number 170202

Bogotá, , Colombia

Sanofi-Aventis Investigational Site Number 203202

Hradec Králové, , Czechia

Sanofi-Aventis Investigational Site Number 203204

Prague, , Czechia

Sanofi-Aventis Investigational Site Number 208202

Frederiksberg, , Denmark

Sanofi-Aventis Investigational Site Number 208201

København NV, , Denmark

Sanofi-Aventis Investigational Site Number 208205

Slagelse, , Denmark

Sanofi-Aventis Investigational Site Number 233201

Pärnu, , Estonia

Sanofi-Aventis Investigational Site Number 233203

Tallinn, , Estonia

Sanofi-Aventis Investigational Site Number 233204

Tartu, , Estonia

Sanofi-Aventis Investigational Site Number 233202

Viljandimaa, , Estonia

Sanofi-Aventis Investigational Site Number 250204

Amiens, , France

Sanofi-Aventis Investigational Site Number 250206

La Rochelle, , France

Sanofi-Aventis Investigational Site Number 250203

Le Creusot, , France

Sanofi-Aventis Investigational Site Number 250201

Nantes, , France

Sanofi-Aventis Investigational Site Number 250202

Pierre-Bénite, , France

Sanofi-Aventis Investigational Site Number 276201

Dresden, , Germany

Sanofi-Aventis Investigational Site Number 276202

Mainz, , Germany

Sanofi-Aventis Investigational Site Number 276204

Saint Ingbert-Oberwürzbach, , Germany

Sanofi-Aventis Investigational Site Number 348205

Balatonfüred, , Hungary

Sanofi-Aventis Investigational Site Number 348202

Budapest, , Hungary

Sanofi-Aventis Investigational Site Number 348207

Budapest, , Hungary

Sanofi-Aventis Investigational Site Number 348204

Debrecen, , Hungary

Sanofi-Aventis Investigational Site Number 348206

Gyula, , Hungary

Sanofi-Aventis Investigational Site Number 348203

Szeged, , Hungary

Sanofi-Aventis Investigational Site Number 348201

Zalaegerszeg, , Hungary

Sanofi-Aventis Investigational Site Number 356210

Ahmedabad, , India

Sanofi-Aventis Investigational Site Number 356206

Bangalore, , India

Sanofi-Aventis Investigational Site Number 356204

Bangalore, , India

Sanofi-Aventis Investigational Site Number 356202

Bangalore, , India

Sanofi-Aventis Investigational Site Number 356201

Belagavi, , India

Sanofi-Aventis Investigational Site Number 356205

Chennai, , India

Sanofi-Aventis Investigational Site Number 356208

Indore, , India

Sanofi-Aventis Investigational Site Number 356203

Karnāl, , India

Sanofi-Aventis Investigational Site Number 356207

Kochi, , India

Sanofi-Aventis Investigational Site Number 356209

Nagpur, , India

Sanofi-Aventis Investigational Site Number 376202

Haifa, , Israel

Sanofi-Aventis Investigational Site Number 376201

Holon, , Israel

Sanofi-Aventis Investigational Site Number 376204

Kfar Saba, , Israel

Sanofi-Aventis Investigational Site Number 376203

Tel Litwinsky, , Israel

Sanofi-Aventis Investigational Site Number 380201

Milan, , Italy

Sanofi-Aventis Investigational Site Number 380202

Perugia, , Italy

Sanofi-Aventis Investigational Site Number 458203

Kelantan, , Malaysia

Sanofi-Aventis Investigational Site Number 458202

Kuala Lumpur, , Malaysia

Sanofi-Aventis Investigational Site Number 484201

Cuernavaca, , Mexico

Sanofi-Aventis Investigational Site Number 484204

Durango, , Mexico

Sanofi-Aventis Investigational Site Number 484203

Guadalajara, , Mexico

Sanofi-Aventis Investigational Site Number 484206

México, , Mexico

Sanofi-Aventis Investigational Site Number 484205

Tlalnepantla, , Mexico

Sanofi-Aventis Investigational Site Number 528203

Amsterdam, , Netherlands

Sanofi-Aventis Investigational Site Number 528202

Groningen, , Netherlands

Sanofi-Aventis Investigational Site Number 528204

Zwijndrecht, , Netherlands

Sanofi-Aventis Investigational Site Number 616202

Krakow, , Poland

Sanofi-Aventis Investigational Site Number 616208

Lubin, , Poland

Sanofi-Aventis Investigational Site Number 616207

Puławy, , Poland

Sanofi-Aventis Investigational Site Number 616206

Płock, , Poland

Sanofi-Aventis Investigational Site Number 616205

Sopot, , Poland

Sanofi-Aventis Investigational Site Number 616201

Szczecin, , Poland

Sanofi-Aventis Investigational Site Number 616203

Zabrze, , Poland

Sanofi-Aventis Investigational Site Number 840226

Ponce, , Puerto Rico

Sanofi-Aventis Investigational Site Number 840216

San Juan, , Puerto Rico

Sanofi-Aventis Investigational Site Number 642204

Brasov, , Romania

Sanofi-Aventis Investigational Site Number 642208

Bucharest, , Romania

Sanofi-Aventis Investigational Site Number 642205

Deva, , Romania

Sanofi-Aventis Investigational Site Number 642203

Iași, , Romania

Sanofi-Aventis Investigational Site Number 642202

Oradea, , Romania

Sanofi-Aventis Investigational Site Number 642206

Târgu Mureş, , Romania

Sanofi-Aventis Investigational Site Number 642207

Timișoara, , Romania

Sanofi-Aventis Investigational Site Number 642201

Timișoara, , Romania

Sanofi-Aventis Investigational Site Number 643202

Saint Petersburg, , Russia

Sanofi-Aventis Investigational Site Number 643203

Saratov, , Russia

Sanofi-Aventis Investigational Site Number 710202

Cape Town, , South Africa

Sanofi-Aventis Investigational Site Number 710201

Durban, , South Africa

Sanofi-Aventis Investigational Site Number 710203

Pretoria, , South Africa

Sanofi-Aventis Investigational Site Number 752204

Gothenburg, , Sweden

Sanofi-Aventis Investigational Site Number 752203

Härnösand, , Sweden

Sanofi-Aventis Investigational Site Number 752205

Luleå, , Sweden

Sanofi-Aventis Investigational Site Number 752202

Malmo, , Sweden

Sanofi-Aventis Investigational Site Number 752201

Stockholm, , Sweden

Sanofi-Aventis Investigational Site Number 158204

Changhua, , Taiwan

Sanofi-Aventis Investigational Site Number 158203

Taichung, , Taiwan

Sanofi-Aventis Investigational Site Number 158201

Taichung R.o.c., , Taiwan

Sanofi-Aventis Investigational Site Number 158202

Tainan Hsien, , Taiwan

Sanofi-Aventis Investigational Site Number 804203

Chernivtsi, , Ukraine

Sanofi-Aventis Investigational Site Number 804201

Kiev, , Ukraine

Sanofi-Aventis Investigational Site Number 804205

Kyiv, , Ukraine

Sanofi-Aventis Investigational Site Number 804202

Kyiv, , Ukraine

Sanofi-Aventis Investigational Site Number 804204

Vinnytsia, , Ukraine

Countries

United States; Argentina; Brazil; Canada; Chile; Colombia; Czechia; Denmark; Estonia; France; Germany; Hungary; India; Israel; Italy; Malaysia; Mexico; Netherlands; Poland; Puerto Rico; Romania; Russia; South Africa; Sweden; Taiwan; Ukraine

References

Riddle MC, Forst T, Aronson R, Sauque-Reyna L, Souhami E, Silvestre L, Ping L, Rosenstock J. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, randomized, placebo-controlled study (GetGoal-Duo 1). Diabetes Care. 2013 Sep;36(9):2497-503. doi: 10.2337/dc12-2462. Epub 2013 Apr 5.

Reference Type: RESULT

PMID: 23564915 (View on PubMed)

Yao J, Zhang M, Zhang X, Zhang J. Impact of Type 2 Diabetes Duration on the Efficacy and Safety of Add-on Lixisenatide in Asian Individuals Receiving Basal Insulin: A Pooled Analysis. Diabetes Ther. 2023 Apr;14(4):653-669. doi: 10.1007/s13300-023-01369-6. Epub 2023 Feb 21.

Reference Type: DERIVED

PMID: 36809495 (View on PubMed)

Davidson JA, Stager W, Paranjape S, Berria R, Leiter LA. Achieving postprandial glucose control with lixisenatide improves glycemic control in patients with type 2 diabetes on basal insulin: a post-hoc analysis of pooled data. Clin Diabetes Endocrinol. 2020 Jan 14;6:2. doi: 10.1186/s40842-019-0088-5. eCollection 2020.

Reference Type: DERIVED

PMID: 31956422 (View on PubMed)

Rosenstock J, Handelsman Y, Vidal J, Ampudia Blasco FJ, Giorgino F, Liu M, Perfetti R, Meier JJ. Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes. Diabetes Obes Metab. 2018 Dec;20(12):2821-2829. doi: 10.1111/dom.13462. Epub 2018 Aug 13.

Reference Type: DERIVED

PMID: 29974618 (View on PubMed)

Charbonnel B, Bertolini M, Tinahones FJ, Domingo MP, Davies M. Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis. J Diabetes Complications. 2014 Nov-Dec;28(6):880-6. doi: 10.1016/j.jdiacomp.2014.07.007. Epub 2014 Jul 18.

Reference Type: DERIVED

PMID: 25130920 (View on PubMed)

Riddle MC, Aronson R, Home P, Marre M, Niemoeller E, Miossec P, Ping L, Ye J, Rosenstock J. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care. 2013 Sep;36(9):2489-96. doi: 10.2337/dc12-2454. Epub 2013 Apr 29.

Reference Type: DERIVED

PMID: 23628617 (View on PubMed)

Other Identifiers

EudraCT : 2008-007335-40

Identifier Type: -

Identifier Source: secondary_id

EFC10781

Identifier Type: -

Identifier Source: org_study_id