Clinical trial NCT01476475: Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Combination Versus Insulin Glargine Alone on Top of Metformin in Type 2 Diabetic Patients
Official title: A Randomized, 24-week, Open-label, 2-arm Parallel-group, Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine on Top of Metformin in Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-11-22
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change in 2-hour Postprandial Plasma Glucose (PPG) From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in 2-hour Plasma Glucose Excursion From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profiles From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in Body Weight From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Average Daily Insulin Glargine Dose at Week 24
timeFrame: Week 24
measure: Change in FPG From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Requiring Rescue Therapy During 24-week Treatment Period
timeFrame: Baseline up to Week 24
measure: Percentage of Participants With HbA1c ≤6.5 % or <7.0 % at Week 24
timeFrame: Week 24
measure: Change in 30-minute and 1-hour PPG From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in 30 Minute and 1-hour Plasma Glucose Excursion From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Reaching HbA1c <7% at Week 24 With no Documented Symptomatic Hypoglycemia During 24-week Treatment Period
timeFrame: Baseline up to Week 24
measure: Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia
timeFrame: First dose of study drug up to 3 days after the last dose administration (maximum of 219 days)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Investigational Site Number 840408
state: Arkansas
city: Paramount
country: United States
facility: Investigational Site Number 840412
state: California
city: Larenceville
country: United States
facility: Investigational Site Number 840401
state: Georgia
city: Roswell
country: United States
facility: Investigational Site Number 840417
state: Georgia
city: Lexington
country: United States
facility: Investigational Site Number 840403
state: Kentucky
city: Hyattsville
country: United States
facility: Investigational Site Number 840404
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 840405
state: Maryland
city: Las Vegas
country: United States
facility: Investigational Site Number 840411
state: Nevada
city: West Seneca
country: United States
facility: Investigational Site Number 840415
state: New York
city: Norman
country: United States
facility: Investigational Site Number 840402
state: Oklahoma
city: Medford
country: United States
facility: Investigational Site Number 840407
state: Oregon
city: Durham
country: United States
facility: Investigational Site Number 840413
state: Pennsylvania
city: Dallas
country: United States
facility: Investigational Site Number 840410
state: Texas
city: Renton
country: United States
facility: Investigational Site Number 840414
state: Washington
city: Santiago
country: Chile
facility: Investigational Site Number 152404
city: Santiago
country: Chile
facility: Investigational Site Number 152405
city: Santiago
country: Chile
facility: Investigational Site Number 152403
city: Santiago
country: Chile
facility: Investigational Site Number 152401
city: Santiago
country: Chile
facility: Investigational Site Number 152402
city: Novy Jicin
country: Czech Republic
facility: Investigational Site Number 203403
city: Plzen
country: Czech Republic
facility: Investigational Site Number 203401
city: Praha 2
country: Czech Republic
facility: Investigational Site Number 203402
city: Praha 8
country: Czech Republic
facility: Investigational Site Number 203405
city: København Nv
country: Denmark
facility: Investigational Site Number 208401
city: Køge
country: Denmark
facility: Investigational Site Number 208404
city: Slagelse
country: Denmark
facility: Investigational Site Number 208402
city: Svendborg
country: Denmark
facility: Investigational Site Number 208403
city: Narbonne
country: France
facility: Investigational Site Number 250402
city: Poitiers Cedex
country: France
facility: Investigational Site Number 250404
city: Vandoeuvre Les Nancy
country: France
facility: Investigational Site Number 250401
city: Dresden
country: Germany
facility: Investigational Site Number 276401
city: Ludwigshafen
country: Germany
facility: Investigational Site Number 276402
city: Oberhausen
country: Germany
facility: Investigational Site Number 276403
city: Balatonfüred
country: Hungary
facility: Investigational Site Number 348401
city: Budapest
country: Hungary
facility: Investigational Site Number 348405
city: Budapest
country: Hungary
facility: Investigational Site Number 348406
city: Debrecen
country: Hungary
facility: Investigational Site Number 348404
city: Szeged
country: Hungary
facility: Investigational Site Number 348402
city: Szeged
country: Hungary
facility: Investigational Site Number 348403
city: Kaunas
country: Lithuania
facility: Investigational Site Number 440401
city: Kaunas
country: Lithuania
facility: Investigational Site Number 440402
city: Kedainiai
country: Lithuania
facility: Investigational Site Number 440403
city: Klaipeda
country: Lithuania
facility: Investigational Site Number 440404
city: Acapulco
country: Mexico
facility: Investigational Site Number 484404
city: Cuernavaca
country: Mexico
facility: Investigational Site Number 484401
city: Durango
country: Mexico
facility: Investigational Site Number 484405
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484402
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484403
city: Bialystok
country: Poland
facility: Investigational Site Number 616405
city: Gdansk
country: Poland
facility: Investigational Site Number 616406
city: Krakow
country: Poland
facility: Investigational Site Number 616403
city: Lodz
country: Poland
facility: Investigational Site Number 616407
city: Pulawy
country: Poland
facility: Investigational Site Number 616404
city: Szczecin
country: Poland
facility: Investigational Site Number 616402
city: Warszawa
country: Poland
facility: Investigational Site Number 616401
city: Brasov
country: Romania
facility: Investigational Site Number 642402
city: Bucuresti
country: Romania
facility: Investigational Site Number 642403
city: Iasi
country: Romania
facility: Investigational Site Number 642405
city: Oradea
country: Romania
facility: Investigational Site Number 642401
city: Targu Mures
country: Romania
facility: Investigational Site Number 642406
city: Timisoara
country: Romania
facility: Investigational Site Number 642404
city: Bratislava
country: Slovakia
facility: Investigational Site Number 703402
city: Kosice
country: Slovakia
facility: Investigational Site Number 703403
city: Kosice
country: Slovakia
facility: Investigational Site Number 703406
city: Moldava Nad Bodvou
country: Slovakia
facility: Investigational Site Number 703404
city: Nitra
country: Slovakia
facility: Investigational Site Number 703405
city: Zilina
country: Slovakia
facility: Investigational Site Number 703401
city: Skellefteå
country: Sweden
facility: Investigational Site Number 752402
city: Stockholm
country: Sweden
facility: Investigational Site Number 752401
city: Växjö
country: Sweden
facility: Investigational Site Number 752403
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.