Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Combination Versus Insulin Glargine Alone on Top of Metformin in Type 2 Diabetic Patients

NCT ID: NCT01476475

Last Updated: 2017-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 323 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-12-31

Brief Summary

Primary Objective:

• The purpose of this study was to compare insulin glargine/ lixisenatide fixed ratio combination (FRC) versus insulin glargine on glycemic control over 24 weeks, as evaluated by glycosylated hemoglobin (HbA1c) reduction in type 2 diabetic participants treated with metformin.

Secondary Objectives:

• To compare insulin glargine/lixisenatide FRC versus insulin glargine over 24 weeks on:

• Glycemic control in relation to a meal as evaluated by post-prandial plasma glucose and glucose excursions during a standardized meal test;
• Percentage of participants reaching HbA1c <7% or ≤6.5%;
• 7-point Self-Monitored Plasma Glucose (SMPG) profile;
• Body weight;
• Insulin glargine dose
• Fasting Plasma Glucose (FPG);
• Percentage of participants requiring rescue therapy during the 24-week open label treatment period;
• To assess safety and tolerability of insulin glargine/lixisenatide FRC.

Detailed Description

Approximately 27 weeks including a 24-week treatment period.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Insulin glargine/Lixisenatide Fixed Ratio Combination (FRC)

FRC injected once daily (QD) for 24 weeks. Dose individually adjusted.

Group Type: EXPERIMENTAL

Insulin glargine /lixisenatide Fixed Ratio Combination

Intervention Type: DRUG

FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using pen-type injector (Tactipen®): 100 U/ml insulin glargine and 50 mcg Lixisenatide (ratio of 2 U/1 mcg). The initial dose was 10 U/5 mcg and then dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L.

Metformin (Background drug)

Intervention Type: DRUG

Pharmaceutical form: Tablet; Route of administration: oral administration. To be kept at stable dose (≥1.5 g/day) throughout the study.

Insulin glargine

Insulin glargine QD for 24 weeks. Dose individually adjusted.

Group Type: ACTIVE_COMPARATOR

Insulin glargine

Intervention Type: DRUG

Insulin glargine (100 U/ml) was self-administered by SC injection before breakfast using pen-type injector (Lantus® Solostar®). The initial daily dose of insulin glargine was 10 U and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L).

Metformin (Background drug)

Intervention Type: DRUG

Pharmaceutical form: Tablet; Route of administration: oral administration. To be kept at stable dose (≥1.5 g/day) throughout the study.

Interventions

Insulin glargine /lixisenatide Fixed Ratio Combination

FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using pen-type injector (Tactipen®): 100 U/ml insulin glargine and 50 mcg Lixisenatide (ratio of 2 U/1 mcg). The initial dose was 10 U/5 mcg and then dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L.

Intervention Type: DRUG

Insulin glargine

Insulin glargine (100 U/ml) was self-administered by SC injection before breakfast using pen-type injector (Lantus® Solostar®). The initial daily dose of insulin glargine was 10 U and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L).

Intervention Type: DRUG

Metformin (Background drug)

Pharmaceutical form: Tablet; Route of administration: oral administration. To be kept at stable dose (≥1.5 g/day) throughout the study.

Intervention Type: DRUG

Other Intervention Names

(HOE901/AVE0010); Lantus

Eligibility Criteria

Inclusion Criteria

• Participants with type 2 diabetes mellitus diagnosed for at least 1 year.
• Metformin treatment at a stable dose of at least 1.5 g/day for at least 3 months prior to screening.

Exclusion Criteria

• Age < legal age of adulthood (18 years).
• Screening HbA1c <7% or >10%.
• Screening FPG >250 mg/dL (>13.9 mmol/L).
• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
• Type 1 diabetes mellitus.
• Treatment with glucose-lowering agent(s) other than metformin in a period of 3 months prior to screening.
• Use of insulin within the last 6 months.
• Previous use of insulin, except for episode(s) of short-term treatment (≤15 consecutive days) due to intercurrent illness.
• Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN) at screening.
• Calcitonin ≥20 pg/ml (5.9 pmol/l) at screening.
• Alanine Transferase (ALT) >3 ULN at screening.
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes).
• Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic or diastolic blood pressure >180 mmHg or >110 mmHg, respectively.
• Within the last 6 months prior to screening: history of heart failure requiring hospitalization, myocardial infarction, or stroke. Planned coronary, carotid or peripheral artery revascularisation procedures.
• Body Mass Index (BMI) ≤20 or >40 kg/m^2.
• Any previous treatment with lixisenatide

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• 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 840408

Little Rock, Arkansas, United States

Investigational Site Number 840412

Paramount, California, United States

Investigational Site Number 840401

Larenceville, Georgia, United States

Investigational Site Number 840417

Roswell, Georgia, United States

Investigational Site Number 840403

Lexington, Kentucky, United States

Investigational Site Number 840404

Hyattsville, Maryland, United States

Investigational Site Number 840405

Rockville, Maryland, United States

Investigational Site Number 840411

Las Vegas, Nevada, United States

Investigational Site Number 840415

West Seneca, New York, United States

Investigational Site Number 840402

Norman, Oklahoma, United States

Investigational Site Number 840407

Medford, Oregon, United States

Investigational Site Number 840413

Durham, Pennsylvania, United States

Investigational Site Number 840410

Dallas, Texas, United States

Investigational Site Number 840414

Renton, Washington, United States

Investigational Site Number 152404

Santiago, , Chile

Investigational Site Number 152405

Santiago, , Chile

Investigational Site Number 152403

Santiago, , Chile

Investigational Site Number 152401

Santiago, , Chile

Investigational Site Number 152402

Santiago, , Chile

Investigational Site Number 203403

Nový Jičín, , Czechia

Investigational Site Number 203401

Pilsen, , Czechia

Investigational Site Number 203402

Prague, , Czechia

Investigational Site Number 203405

Prague, , Czechia

Investigational Site Number 208401

København NV, , Denmark

Investigational Site Number 208404

Køge, , Denmark

Investigational Site Number 208402

Slagelse, , Denmark

Investigational Site Number 208403

Svendborg, , Denmark

Investigational Site Number 250402

Narbonne, , France

Investigational Site Number 250404

Poitiers, , France

Investigational Site Number 250401

Vandœuvre-lès-Nancy, , France

Investigational Site Number 276401

Dresden, , Germany

Investigational Site Number 276402

Ludwigshafen, , Germany

Investigational Site Number 276403

Oberhausen, , Germany

Investigational Site Number 348401

Balatonfüred, , Hungary

Investigational Site Number 348405

Budapest, , Hungary

Investigational Site Number 348406

Budapest, , Hungary

Investigational Site Number 348404

Debrecen, , Hungary

Investigational Site Number 348402

Szeged, , Hungary

Investigational Site Number 348403

Szeged, , Hungary

Investigational Site Number 440401

Kaunas, , Lithuania

Investigational Site Number 440402

Kaunas, , Lithuania

Investigational Site Number 440403

Kėdainiai, , Lithuania

Investigational Site Number 440404

Klaipėda, , Lithuania

Investigational Site Number 484404

Acapulco, , Mexico

Investigational Site Number 484401

Cuernavaca, , Mexico

Investigational Site Number 484405

Durango, , Mexico

Investigational Site Number 484402

Guadalajara, , Mexico

Investigational Site Number 484403

Guadalajara, , Mexico

Investigational Site Number 616405

Bialystok, , Poland

Investigational Site Number 616406

Gdansk, , Poland

Investigational Site Number 616403

Krakow, , Poland

Investigational Site Number 616407

Lodz, , Poland

Investigational Site Number 616404

Puławy, , Poland

Investigational Site Number 616402

Szczecin, , Poland

Investigational Site Number 616401

Warsaw, , Poland

Investigational Site Number 642402

Brasov, , Romania

Investigational Site Number 642403

Bucharest, , Romania

Investigational Site Number 642405

Iași, , Romania

Investigational Site Number 642401

Oradea, , Romania

Investigational Site Number 642406

Târgu Mureş, , Romania

Investigational Site Number 642404

Timișoara, , Romania

Investigational Site Number 703402

Bratislava, , Slovakia

Investigational Site Number 703403

Košice, , Slovakia

Investigational Site Number 703406

Košice, , Slovakia

Investigational Site Number 703404

Moldava nad Bodvou, , Slovakia

Investigational Site Number 703405

Nitra, , Slovakia

Investigational Site Number 703401

Žilina, , Slovakia

Investigational Site Number 752402

Skellefteå, , Sweden

Investigational Site Number 752401

Stockholm, , Sweden

Investigational Site Number 752403

Vaxjo, , Sweden

Countries

United States; Chile; Czechia; Denmark; France; Germany; Hungary; Lithuania; Mexico; Poland; Romania; Slovakia; Sweden

References

Rosenstock J, Diamant M, Aroda VR, Silvestre L, Souhami E, Zhou T, Perfetti R, Fonseca V; LixiLan PoC Study Group. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial. Diabetes Care. 2016 Sep;39(9):1579-86. doi: 10.2337/dc16-0046. Epub 2016 Jun 9.

Reference Type: RESULT

PMID: 27284114 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/?term=27284114

Related Info

Other Identifiers

2011-002090-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1121-7111

Identifier Type: OTHER

Identifier Source: secondary_id

ACT12374

Identifier Type: -

Identifier Source: org_study_id