Clinical trial NCT01117350: Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure
Official title: A 24-week, Multicenter, International, Randomized (1:1), Parallel-group, Open-label, Comparative Study of Insulin Glargine Versus Liraglutide in Insulin-naïve Patients With Type 2 Diabetes Treated With Oral Agents and Not Adequately Controlled, Followed by a 24-week Extension Period With Insulin Glargine for Patients Not Adequately Controlled With Liraglutide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-05-05
Enrollment: 978
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary objective:

To demonstrate the superiority of insulin glargine over liraglutide in terms of percentage of patients reaching a Glycosylated Haemoglobin (HbA1c) \< 7% at the end of the comparative period (24 weeks) in Type 2 diabetic patients failing lifestyle management and oral agents

Secondary objectives of the comparative period (24 weeks):

\>To assess the effect of insulin glargine in comparison with liraglutide on:

* HbA1c level
* Percentage of patients whose HbA1c has decreased but remains \>= 7% at the end of the comparative period
* Percentage of patients whose HbA1c has increased at the end of the comparative period
* Fasting Plasma Glucose (FPG)
* 7-point Plasma Glucose (PG) profiles
* Hypoglycemia occurrence
* Body weight
* Adverse events

Objectives of the extension period (24 weeks):

\>To assess the effect of insulin glargine in patients not adequately controlled with liraglutide on:

* HbA1c level
* FPG
* 7-point PG profiles
* Hypoglycemia occurrence
* Body weight
* Adverse events

Detailed description: Maximum estimated study duration per patient: either 27 weeks (patients randomized to insulin glargine arm) or 51 weeks (patients randomized to liraglutide arm) broken down as follow:

* A 2-week of screening period,
* A 24-week comparative period,
* A 24-week extension period (only for patients treated with liraglutide, not adequately controlled at the end of the comparative period),
* A 1-week follow-up period

Eligibility criteria: Inclusion criteria (comparative period):

* Patients With Type 2 Diabetes diagnosed for at least 1 year,
* Treated with lifestyle interventions and metformin at the maximum tolerated dosage (with a minimum daily dosage of 1g), either alone or in combination with an oral insulin secretagogue (sulfonylurea, glinide or DiPeptidyl Peptidase IV inhibitor), for more than 3 months,
* 7.5% \< HbA1c \<= 12%,
* Body Mass Index (BMI) between 25 and 40 kg/m2 inclusively,
* Ability and willingness to perform PG (Plasma Glucose) self monitoring using the sponsor-provided glucose meter and to complete the patient diary,
* Willingness and ability to comply with the study protocol,
* Signed informed consent obtained prior to any study procedure.

Inclusion criteria (extension period):

* Patients treated with liraglutide (at the maximal tolerated dosage), having a mean FPG ≥ 250 mg/dL at visit 10 (Week 12) or visit 11 (Week 18), or a HbA1c≥ 7% at visit 12 (Week 24)
* Dosage of metformin compliant with the inclusion criteria of visit 1 (i.e. maximum tolerated dosage, with a minimum daily dosage of 1g), and maintained stable during the comparative period.

Exclusion criteria:

* Previous treatment with Glucagon Like Peptide-1 analogues or insulin in the past year (except in case of temporary treatment for gestational diabetes, surgery, hospitalization...),
* Treatment with thiazolidinediones or α-Glucosidases inhibitors within 3 months prior to study entry,
* Diabetes other than Type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake),
* Pregnant women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method),
* Lactating women,
* Hospitalized patients (except hospitalization for routine diabetes check-up),
* Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by a retina examination within 2 years prior to study entry,
* Impaired renal function (creatinine clearance \< 60 mL/mn),
* Impaired hepatic function (Alanine Aminotransferase, Aspartate Aminotransferase 2.5 times the upper limit of normal range),
* Personal or family history of medullary thyroid carcinoma,
* Multiple endocrine neoplasia syndrome type 2,
* Severe gastro-intestinal disease (including inflammatory bowel disease or diabetic gastroparesis),
* Congestive heart failure,
* History of acute pancreatitis,
* Treatment with corticosteroids with potential systemic action for more than 10 days within 3 months prior to study entry,
* Alcohol or drug abuse in the past 5 years,
* History of sensitivity to the study drugs or to drugs with a similar chemical structure.
* Night shift worker,
* Presence of any condition (medical, psychological, social or geographical), current or anticipated that would compromise the patients safety or limit the patient successful participation in the study,
* Participation in a clinical trial (drug or device) within 3 months prior to study entry,
* Refusal or inability to give informed consent to participate in the study,
* Patient is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

Additional exclusion criteria for the extension period:

* Treatment with oral antidiabetic drugs other than metformin and patient's usual sulfonylurea if any, or with insulin during the comparative period (except in case of an emergency, for a period of time less than 7 days),
* Treatment with corticosteroids with potential systemic action within the last 3 months of the comparative period.
* History of sensitivity to insulin glargine.

Primary outcomes:
measure: Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period
timeFrame: week 12, week 24
Secondary outcomes:
measure: Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period
timeFrame: baseline (week -2), week 12, week 24
measure: Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period
timeFrame: baseline (week -2), week 12, week 24
measure: Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period
timeFrame: baseline (week -2), week 12, week 24
measure: Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period
timeFrame: week 24, week 36, week 48
measure: Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period
timeFrame: week 36, week 48
measure: Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period
timeFrame: baseline (week 0), week 6, week 12, week 18, week 24
measure: Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period
timeFrame: week 24, week 30, week 36, week 48
measure: Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period
timeFrame: baseline (week 0), week 12, week 24
measure: Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period
timeFrame: week 24, week 36, week 48
measure: Body Weight: Change From Baseline to the End of the Comparative Period
timeFrame: baseline (week 0), week 2, week 6, week 12, week 18, week 24
measure: Body Weight: Change From Beginning to End of the Extension Period
timeFrame: week 24, week 30, week 36, week 48
measure: Daily Dose of Insulin Glargine
timeFrame: week 1, week 2, week 6, week 12, week 24
measure: Daily Dose of Liraglutide
timeFrame: week 1, week 2, week 6, week 12, week 24
measure: Daily Dose of Insulin Glargine Administered During the Extension Period
timeFrame: week 30, week 36, week 48
measure: Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period
timeFrame: all across the comparative period (from week 0 to week 24)
measure: Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period
timeFrame: all across the extension period (from week 24 to week 48)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840023
state: Alabama
city: Goodyear
country: United States
facility: Investigational Site Number 840002
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 840047
state: Arizona
city: La Jolla
country: United States
facility: Investigational Site Number 840017
state: California
city: La Mesa
country: United States
facility: Investigational Site Number 840036
state: California
city: Loma Linda
country: United States
facility: Investigational Site Number 840037
state: California
city: Long Beach
country: United States
facility: Investigational Site Number 840045
state: California
city: Mission Hills
country: United States
facility: Investigational Site Number 840048
state: California
city: Mission Viejo
country: United States
facility: Investigational Site Number 840033
state: California
city: Palm Springs
country: United States
facility: Investigational Site Number 840019
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840039
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840042
state: California
city: Tustin
country: United States
facility: Investigational Site Number 840043
state: California
city: Denver
country: United States
facility: Investigational Site Number 840028
state: Colorado
city: Grand Junction
country: United States
facility: Investigational Site Number 840034
state: Colorado
city: Longmont
country: United States
facility: Investigational Site Number 840026
state: Colorado
city: Lawrenceville
country: United States
facility: Investigational Site Number 840022
state: Georgia
city: Roswell
country: United States
facility: Investigational Site Number 840029
state: Georgia
city: Arlington Heights
country: United States
facility: Investigational Site Number 840009
state: Illinois
city: Springfield
country: United States
facility: Investigational Site Number 840051
state: Illinois
city: Indianapolis
country: United States
facility: Investigational Site Number 840050
state: Indiana
city: Kansas City
country: United States
facility: Investigational Site Number 840031
state: Kansas
city: Paducah
country: United States
facility: Investigational Site Number 840004
state: Kentucky
city: Rockville
country: United States
facility: Investigational Site Number 840010
state: Maryland
city: Eagan
country: United States
facility: Investigational Site Number 840038
state: Minnesota
city: Minneapolis
country: United States
facility: Investigational Site Number 840030
state: Minnesota
city: St Louis
country: United States
facility: Investigational Site Number 840012
state: Missouri
city: St. Louis
country: United States
facility: Investigational Site Number 840044
state: Missouri
city: Atco
country: United States
facility: Investigational Site Number 840015
state: New Jersey
city: Blackwood
country: United States
facility: Investigational Site Number 840008
state: New Jersey
city: Mineola
country: United States
facility: Investigational Site Number 840027
state: New York
city: Staten Island
country: United States
facility: Investigational Site Number 840011
state: New York
city: Hickory
country: United States
facility: Investigational Site Number 840005
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigational Site Number 840052
state: North Carolina
city: Fargo
country: United States
facility: Investigational Site Number 840049
state: North Dakota
city: Bryan
country: United States
facility: Investigational Site Number 840006
state: Ohio
city: Cincinnati
country: United States
facility: Investigational Site Number 840035
state: Ohio
city: Carnegie
country: United States
facility: Investigational Site Number 840016
state: Pennsylvania
city: Uniontown
country: United States
facility: Investigational Site Number 840020
state: Pennsylvania
city: Rapid City
country: United States
facility: Investigational Site Number 840024
state: South Dakota
city: Dallas
country: United States
facility: Investigational Site Number 840001
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840007
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840013
state: Texas
city: Renton
country: United States
facility: Investigational Site Number 840014
state: Washington
city: Spokane
country: United States
facility: Investigational Site Number 840046
state: Washington
city: Salzburg
country: Austria
facility: Investigational Site Number 040-006
city: Salzburg
country: Austria
facility: Investigational Site Number 040-007
city: Stockerau
country: Austria
facility: Investigational Site Number 040-003
city: Vienna
country: Austria
facility: Investigational Site Number 040-005
city: Vienna
country: Austria
facility: Investigational Site Number 040-002
city: Vienna
country: Austria
facility: Investigational Site Number 040-001
city: Vienna
country: Austria
facility: Investigational Site Number 040-004
city: Belém
country: Brazil
facility: Investigational Site Number 076-004
city: Fortaleza
country: Brazil
facility: Investigational Site Number 076-007
city: Fortaleza
country: Brazil
facility: Investigational Site Number 076-001
city: Fortaleza
country: Brazil
facility: Investigational Site Number 076-006
city: Marília
country: Brazil
facility: Investigational Site Number 076-005
city: São Paulo
country: Brazil
facility: Investigational Site Number 076-002
city: Mississauga
country: Canada
facility: Investigational Site Number 124-003
city: Montreal
country: Canada
facility: Investigational Site Number 124-001
city: Montreal
country: Canada
facility: Investigational Site Number 124-006
city: Toronto
country: Canada
facility: Investigational Site Number 124-004
city: Vancouver
country: Canada
facility: Investigational Site Number 124-008
city: Victoria
country: Canada
facility: Investigational Site Number 124-007
city: Hradec Kralove
country: Czech Republic
facility: Investigational Site Number 203001
city: Krnov
country: Czech Republic
facility: Investigational Site Number 203003
city: Kromeriz
country: Czech Republic
facility: Investigational Site Number 203005
city: Olomouc
country: Czech Republic
facility: Investigational Site Number 203002
city: Praha 5
country: Czech Republic
facility: Investigational Site Number 203006
city: Harjavalta
country: Finland
facility: Investigational Site Number 246003
city: Kuopio
country: Finland
facility: Investigational Site Number 246001
city: Oulu
country: Finland
facility: Investigational Site Number 246002
city: Turku
country: Finland
facility: Investigational Site Number 246004
city: Annecy
country: France
facility: Investigational Site Number 250-007
city: Bois Guillaume Cedex
country: France
facility: Investigational Site Number 250-017
city: Boulogne Billancourt
country: France
facility: Investigational Site Number 250-003
city: Brest
country: France
facility: Investigational Site Number 250-011
city: Cahors Cedex 9
country: France
facility: Investigational Site Number 250-008
city: Corbeil Essonnes
country: France
facility: Investigational Site Number 250-012
city: La Rochelle Cedex 1
country: France
facility: Investigational Site Number 250-009
city: Le Creusot
country: France
facility: Investigational Site Number 250-004
city: Mantes La Jolie
country: France
facility: Investigational Site Number 250-006
city: Nanterre
country: France
facility: Investigational Site Number 250-021
city: Strasbourg
country: France
facility: Investigational Site Number 250022
city: Strasbourg
country: France
facility: Investigational Site Number 250-020
city: Toulouse
country: France
facility: Investigational Site Number 250-002
city: Venissieux
country: France
facility: Investigational Site Number 250-016
city: Athens
country: Greece
facility: Investigational Site Number 300003
city: Athens
country: Greece
facility: Investigational Site Number 300004
city: Haidari, Athens
country: Greece
facility: Investigational Site Number 300001
city: Dublin 4
country: Ireland
facility: Investigational Site Number 372001
city: Hadera
country: Israel
facility: Investigational Site Number 376004
city: Petah Tiqwa
country: Israel
facility: Investigational Site Number 376002
city: Tel-Aviv
country: Israel
facility: Investigational Site Number 376003
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484004
city: Mexico
country: Mexico
facility: Investigational Site Number 484001
city: Mexico
country: Mexico
facility: Investigational Site Number 484002
city: Zapopan
country: Mexico
facility: Investigational Site Number 484003
city: Beek
country: Netherlands
facility: Investigational Site Number 528001
city: Enschede
country: Netherlands
facility: Investigational Site Number 528006
city: Hoogeveen
country: Netherlands
facility: Investigational Site Number 528002
city: Nijverdal
country: Netherlands
facility: Investigational Site Number 528007
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528003
city: s-Hertogenbosch
country: Netherlands
facility: Investigational Site Number 528004
city: Woerden
country: Netherlands
facility: Investigational Site Number 528005
city: Kazan
country: Russian Federation
facility: Investigational Site Number 643-009
city: Kirov
country: Russian Federation
facility: Investigational Site Number 643008
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: Samara
country: Russian Federation
facility: Investigational Site Number 643006
city: Samara
country: Russian Federation
facility: Investigational Site Number 643007
city: Saratov
country: Russian Federation
facility: Investigational Site Number 643005
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643004
city: St-Ptetersburg
country: Russian Federation
facility: Investigational Site Number 643003
city: Bratislava
country: Slovakia
facility: Investigational Site Number 703002
city: Kosice
country: Slovakia
facility: Investigational Site Number 703004
city: Nitra
country: Slovakia
facility: Investigational Site Number 703001
city: Nove Mesto nad Vahom
country: Slovakia
facility: Investigational Site Number 703005
city: Zilina
country: Slovakia
facility: Investigational Site Number 703003
city: Bilbao
country: Spain
facility: Investigational Site Number 724007
city: Cádiz
country: Spain
facility: Investigational Site Number 724006
city: Las Palmas de Gran Canaria
country: Spain
facility: Investigational Site Number 724001
city: LLeida
country: Spain
facility: Investigational Site Number 724005
city: Madrid
country: Spain
facility: Investigational Site Number 724008
city: Málaga
country: Spain
facility: Investigational Site Number 724003
city: Sabadell
country: Spain
facility: Investigational Site Number 724009
city: Valencia
country: Spain
facility: Investigational Site Number 721002
city: Valencia
country: Spain
facility: Investigational Site Number 724004
city: Vigo
country: Spain
facility: Investigational Site Number 724010
city: Göteborg
country: Sweden
facility: Investigational Site Number 752-002
city: Karlskoga
country: Sweden
facility: Investigational Site Number 752-005
city: Motala
country: Sweden
facility: Investigational Site Number 752-006
city: Stockholm
country: Sweden
facility: Investigational Site Number 752-001
city: Ängelholm
country: Sweden
facility: Investigational Site Number 752-03
city: Örebro
country: Sweden
facility: Investigational Site Number 752-007
city: Antalya
country: Turkey
facility: Investigational Site Number 792-001
city: Istanbul
country: Turkey
facility: Investigational Site Number 792-002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: