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

NCT01476475 | Completed Phase 2 Results DMC

• 3 other identifiers: ACT123742011-002090-36U1111-1121-7111
• Study Type: interventional
• Target: 323
• Locations: 13 countries
• Sites: 70

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c From Baseline to Week 24

  Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of investigational medicinal product (IMP).

  Baseline, Week 24

Secondary Outcomes (13)

• Change in 2-hour Postprandial Plasma Glucose (PPG) From Baseline to Week 24

  Baseline, Week 24

• Change in 2-hour Plasma Glucose Excursion From Baseline to Week 24

  Baseline, Week 24

• Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profiles From Baseline to Week 24

  Baseline, Week 24

• Change in Body Weight From Baseline to Week 24

  Baseline, Week 24

• Average Daily Insulin Glargine Dose at Week 24

  Week 24

Study Arms (2)

Insulin glargine/Lixisenatide Fixed Ratio Combination (FRC)

EXPERIMENTAL

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

Drug: Insulin glargine /lixisenatide Fixed Ratio Combination; Drug: Metformin (Background drug)

Insulin glargine

ACTIVE COMPARATOR

Insulin glargine QD for 24 weeks. Dose individually adjusted.

Drug: Insulin glargine; Drug: Metformin (Background drug)

Interventions

Insulin glargine /lixisenatide Fixed Ratio Combination 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.

Also known as: (HOE901/AVE0010)

Insulin glargine/Lixisenatide Fixed Ratio Combination (FRC)

Insulin glargine 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).

Also known as: Lantus

Insulin glargine

Metformin (Background drug) 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/Lixisenatide Fixed Ratio Combination (FRC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (70)

Investigational Site Number 840408

Little Rock, Arkansas, 72205, United States

Location

Investigational Site Number 840412

Paramount, California, 90723, United States

Location

Investigational Site Number 840401

Larenceville, Georgia, 30045, United States

Location

Investigational Site Number 840417

Roswell, Georgia, 30076, United States

Location

Investigational Site Number 840403

Lexington, Kentucky, 40504, United States

Location

Investigational Site Number 840404

Hyattsville, Maryland, 20782, United States

Location

Investigational Site Number 840405

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 840411

Las Vegas, Nevada, 89148, United States

Location

Investigational Site Number 840415

West Seneca, New York, 14224, United States

Location

Investigational Site Number 840402

Norman, Oklahoma, 73069, United States

Location

Investigational Site Number 840407

Medford, Oregon, 97504, United States

Location

Investigational Site Number 840413

Durham, Pennsylvania, 27713, United States

Location

Investigational Site Number 840410

Dallas, Texas, 75230, United States

Location

Investigational Site Number 840414

Renton, Washington, 98055, United States

Location

Investigational Site Number 152404

Santiago, 7500347, Chile

Location

Investigational Site Number 152405

Santiago, 7500347, Chile

Location

Investigational Site Number 152403

Santiago, 7500710, Chile

Location

Investigational Site Number 152401

Santiago, 7980378, Chile

Location

Investigational Site Number 152402

Santiago, 8320000, Chile

Location

Investigational Site Number 203403

Nový Jičín, 74101, Czechia

Location

Investigational Site Number 203401

Pilsen, 32600, Czechia

Location

Investigational Site Number 203402

Prague, 12808, Czechia

Location

Investigational Site Number 203405

Prague, 18100, Czechia

Location

Investigational Site Number 208401

København NV, 2400, Denmark

Location

Investigational Site Number 208404

Køge, 4600, Denmark

Location

Investigational Site Number 208402

Slagelse, 4200, Denmark

Location

Investigational Site Number 208403

Svendborg, 5700, Denmark

Location

Investigational Site Number 250402

Narbonne, 11018, France

Location

Investigational Site Number 250404

Poitiers, 86021, France

Location

Investigational Site Number 250401

Vandœuvre-lès-Nancy, 54511, France

Location

Investigational Site Number 276401

Dresden, 01307, Germany

Location

Investigational Site Number 276402

Ludwigshafen, 67059, Germany

Location

Investigational Site Number 276403

Oberhausen, 46045, Germany

Location

Investigational Site Number 348401

Balatonfüred, 8230, Hungary

Location

Investigational Site Number 348405

Budapest, 1041, Hungary

Location

Investigational Site Number 348406

Budapest, 1212, Hungary

Location

Investigational Site Number 348404

Debrecen, 4043, Hungary

Location

Investigational Site Number 348402

Szeged, 6720, Hungary

Location

Investigational Site Number 348403

Szeged, 6722, Hungary

Location

Investigational Site Number 440401

Kaunas, LT-49456, Lithuania

Location

Investigational Site Number 440402

Kaunas, LT-51270, Lithuania

Location

Investigational Site Number 440403

Kėdainiai, LT-57164, Lithuania

Location

Investigational Site Number 440404

Klaipėda, LT-92304, Lithuania

Location

Investigational Site Number 484404

Acapulco, 39670, Mexico

Location

Investigational Site Number 484401

Cuernavaca, 62250, Mexico

Location

Investigational Site Number 484405

Durango, 34270, Mexico

Location

Investigational Site Number 484402

Guadalajara, 44210, Mexico

Location

Investigational Site Number 484403

Guadalajara, 44656, Mexico

Location

Investigational Site Number 616405

Bialystok, 15-435, Poland

Location

Investigational Site Number 616406

Gdansk, 80-847, Poland

Location

Investigational Site Number 616403

Krakow, 31-548, Poland

Location

Investigational Site Number 616407

Lodz, 94-074, Poland

Location

Investigational Site Number 616404

Puławy, 24-100, Poland

Location

Investigational Site Number 616402

Szczecin, 70-506, Poland

Location

Investigational Site Number 616401

Warsaw, 02-507, Poland

Location

Investigational Site Number 642402

Brasov, 500365, Romania

Location

Investigational Site Number 642403

Bucharest, 020475, Romania

Location

Investigational Site Number 642405

Iași, 700547, Romania

Location

Investigational Site Number 642401

Oradea, 410169, Romania

Location

Investigational Site Number 642406

Târgu Mureş, 540142, Romania

Location

Investigational Site Number 642404

Timișoara, 300133, Romania

Location

Investigational Site Number 703402

Bratislava, 85101, Slovakia

Location

Investigational Site Number 703403

Košice, 04001, Slovakia

Location

Investigational Site Number 703406

Košice, 04013, Slovakia

Location

Investigational Site Number 703404

Moldava nad Bodvou, 04525, Slovakia

Location

Investigational Site Number 703405

Nitra, 94911, Slovakia

Location

Investigational Site Number 703401

Žilina, 01001, Slovakia

Location

Investigational Site Number 752402

Skellefteå, 931 32, Sweden

Location

Investigational Site Number 752401

Stockholm, 171 76, Sweden

Location

Investigational Site Number 752403

Vaxjo, 351 85, Sweden

Location

Related Publications (1)

• 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.

  PMID: 27284114 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Glargine; lixisenatide; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2011
• First Posted: November 22, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 10, 2017
• Results First Posted: February 10, 2017

Record last verified: 2016-12

Locations

CL (5); PL (7); US (14); CZ (4); LI (4); SE (3); HU (6); RO (6); DK (4); DE (3); SL (6); ME (5); FR (3)