Insulins Glargine and gluLisine strAtegy Versus Premixed Insulin strAteGy: a cOmparative Study

NCT01121835 | Completed Phase 4

• 3 other identifiers: LANTU_C_045892009-018172-33U1111-1116-9859
• Study Type: interventional
• Target: 934
• Locations: 16 countries
• Sites: 96

Brief Summary

Primary Objective: To demonstrate the superiority of a strategy with insulin glargine in comparison with a strategy including the premixed insulin in term of percentage of patients reaching HbA1c (glycosylated hemoglobin) below 7% at the end of treatment and who do not experience documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) below 56 mg/dL (3.1 mmol/L)) over a 24-week treatment period, in Type 2 diabetes patients failing lifestyle management and oral agents. Secondary Objectives: To assess the effect of insulin glargine in comparison with premixed insulin on :

• Evolution of HbA1c level during the treatment period Percentage of patients who reach the target of HbA1c \< 7 % and who do not experience documented symptomatic hypoglycemia confirmed by a Plasma Glucose (PG) below 70 mg/dL (3.9 mmol/L)
• Percentage of patients who reach the target of HbA1c \< 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 56 mg/dL (3.1 mmol/L) \>Percentage of patients who reach the target of HbA1c \< 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 70 mg/dL (3.9 mmol/L) \>Evolution of Fasting Plasma Glucose Evolution of 7-point plasma glucose profiles
• Evolution of weight
• Hypoglycemia occurrence
• Dose of insulins
• Evolution of liver function
• Overall safety

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with Glycosylated Haemoglobin (HbA1c) <7% with no documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) ≤ 56 mg/dL [3.1 mmol/L]

  From baseline (visit 2, week 0) to visit 14 (week 24)

Secondary Outcomes (7)

• 7-point plasma glucose (PG) profile recorded on 3 consecutive days

  From baseline (visit 2, week 0) to visit 14 (week 24)

• Self-monitored PG (Plasma Glucose) values over 3 consecutive days

  before visit 4 (week 2)

• Self-monitored PG (Plasma Glucose) values over 3 consecutive days

  before visit 8 (week 6)

• Self-monitored PG (Plasma Glucose) values over 3 consecutive days

  before visit 12 (week 16)

• Weight and supine blood pressure

  From baseline (visit 2, week 0) to visit 14 (week 24)

Study Arms (2)

Insulin glargine

EXPERIMENTAL

Administered once a day in the evening, at the same time every day. The starting daily dose is 0.2 U/Kg of body weight or 12 U, at the investigator's decision. Insulin glulisine is administered for patients of the insulin glargine group requiring insulin glulisine at week 12 (visit 11). Insulin glulisine is administered prior (10-15 min) to the main meal of the day, which is the meal with highest Post-Prandial Plasma Glucose (PPPG) on the 3 profiles performed before week 12. Starting dose is of 4 units per day.

Drug: INSULIN GLARGINE; Drug: INSULIN GLULISINE

Premixed insulin

EXPERIMENTAL

administered once a day (in the evening at dinner) or twice a day (in the morning before breakfast and in the evening at dinner). Starting daily dose will be 6 U at breakfast and 6 U at dinner, if administered twice a day or 12 U at dinner if administered once a day

Drug: PREMIXED INSULIN

Interventions

INSULIN GLARGINE DRUG

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous injection Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 ml)

Insulin glargine

INSULIN GLULISINE DRUG

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 mL)

Insulin glargine

PREMIXED INSULIN DRUG

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: - 30% soluble insulin aspart and 70 % protamine-crystallised insulin aspart in pre-filled Flexpen for all the countries except Mexico * 25 % insulin lispro solution and 75% insulin lispro protamine in cartridges for Humapen Luxura for Mexico only

Premixed insulin

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes diagnosed for more than 1 year
• Insulin naïve
• Treated with lifestyle interventions and oral antidiabetic drugs, at least metformin at the maximum tolerated dose (with a minimum dose of 1g/day), for at least 3 months
• HbA1c ≥ 7.0 % and ≤ 10.5%
• Body mass index (BMI) ≤ 40 kg/m2
• Ability and willingness to perform plasma glucose (PG) 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 any study procedure

You may not qualify if:

• Treatment with glucagon-like peptide-1 (GLP-1) agonists in the 3 months prior to study entry
• Previous treatment with insulin (except for treatment of gestational diabetes or brief treatment with insulin for less than 1 week)
• Diabetes other than type 2 diabetes (e.g. type 1 diabetes, diabetes secondary to pancreatic disorders, drug or chemical agent intake)
• Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method)
• Hospitalized patient (except 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 retina examination, in the 2 years prior to study entry
• History of sensitivity to the study drugs or to drugs with a similar chemical structure
• Impaired renal function: creatinine clearance \< 60ml/min
• Impaired liver function (ALT, AST \> 3 x upper limit of normal range)
• Severe gastro-intestinal disease
• Treatment with corticosteroids with potential systemic action within the 3 months prior to study entry
• Likelihood of requiring treatments during the study which are not permitted
• Treatment with an investigational product in the 30 days prior to study entry
• Alcohol or drug abuse within the last 5 years
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (96)

Investigational Site Number 040-004

Sankt Stefan, A-8511, Austria

Location

Investigational Site Number 040-002

Vienna, A-1030, Austria

Location

Investigational Site Number 040-001

Vienna, Austria

Location

Investigational Site Number 040-003

Vienna, Austria

Location

Investigational Site Number 076002

Belém, 66073-000, Brazil

Location

Investigational Site Number 076005

Curitiba, 80060-900, Brazil

Location

Investigational Site Number 076004

Fortaleza, 60430-370, Brazil

Location

Investigational Site Number 076001

Porto Alegre, 90035-001, Brazil

Location

Investigational Site Number 076003

São Paulo, 04024-002, Brazil

Location

Investigational Site Number 156004

Beijing, China

Location

Investigational Site Number 156005

Beijing, China

Location

Investigational Site Number 156006

Beijing, China

Location

Investigational Site Number 156011

Chongqing, China

Location

Investigational Site Number 156009

Dalian, China

Location

Investigational Site Number 156008

Guangzhou, China

Location

Investigational Site Number 156012

Haikou, China

Location

Investigational Site Number 156007

Nanjing, China

Location

Investigational Site Number 156001

Shanghai, China

Location

Investigational Site Number 156002

Shanghai, China

Location

Investigational Site Number 156003

Shanghai, China

Location

Investigational Site Number 156010

Shenyang, China

Location

Investigational Site Number 170001

Bogotá, Colombia

Location

Investigational Site Number 170002

Bogotá, Colombia

Location

Investigational Site Number 170003

Bucaramanga, Colombia

Location

Investigational Site Number 170005

Manizales, 170, Colombia

Location

Investigational Site Number 170004

Pereira, 170, Colombia

Location

Investigational Site Number 208-001

Hvidovre, 2650, Denmark

Location

Investigational Site Number 208-003

København NV, 2400, Denmark

Location

Investigational Site Number 208-002

København S, 2300, Denmark

Location

Investigational Site Number 300006

Alexandroupoli, 68100, Greece

Location

Investigational Site Number 300001

Athens, Greece

Location

Investigational Site Number 300002

Athens, Greece

Location

Investigational Site Number 300003

Athens, Greece

Location

Investigational Site Number 300004

Athens, Greece

Location

Investigational Site Number 300005

Irakleio, 71001, Greece

Location

Investigational Site Number 300011

Maroussi, Athens, 15123, Greece

Location

Investigational Site Number 300008

Thessaloniki, 546 36, Greece

Location

Investigational Site Number 300010

Thessaloniki, 56429, Greece

Location

Investigational Site Number 300007

Thessaloniki, 57010, Greece

Location

Investigational Site Number 356008

Bangalore, 560043, India

Location

Investigational Site Number 356003

Bangalore, 560052, India

Location

Investigational Site Number 356007

Bangalore, 560092, India

Location

Investigational Site Number 356006

Bhubaneshwar, 751019, India

Location

Investigational Site Number 356001

Hyderabad, 500034, India

Location

Investigational Site Number 356005

Hyderabad, 500034, India

Location

Investigational Site Number 356004

Trivandrum, India

Location

Investigational Site Number 380-010

Catania, 95122, Italy

Location

Investigational Site Number 380-008

Catania, 95124, Italy

Location

Investigational Site Number 380-006

Colleferro, 00034, Italy

Location

Investigational Site Number 380-007

Foggia, 71100, Italy

Location

Investigational Site Number 380-005

Forlì, Italy

Location

Investigational Site Number 380-001

Genova, 16132, Italy

Location

Investigational Site Number 380-011

Merano, 39100, Italy

Location

Investigational Site Number 380-009

Napoli, 80131, Italy

Location

Investigational Site Number 380-012

Napoli, 80131, Italy

Location

Investigational Site Number 380-004

Parma, 43100, Italy

Location

Investigational Site Number 001

Kuwait City, Kuwait

Location

Investigational Site Number 484004

Aguascalientes, 20020, Mexico

Location

Investigational Site Number 484001

Aguascalientes, 20230, Mexico

Location

Investigational Site Number 484003

Guadalajara, 44650, Mexico

Location

Investigational Site Number 484002

Guadalajara, 44680, Mexico

Location

Investigational Site Number 484005

Puebla City, 72000, Mexico

Location

Investigational Site Number 642001

Iași, 700111, Romania

Location

Investigational Site Number 642002

Iași, Romania

Location

Investigational Site Number 642003

Oradea, 410169, Romania

Location

Investigational Site Number 410004

Ansan-si, Kyouggi-do, South Korea

Location

Investigational Site Number 410003

Koyang-si, South Korea

Location

Investigational Site Number 410001

Seoul, South Korea

Location

Investigational Site Number 410002

Seoul, South Korea

Location

Investigational Site Number 724001

Ávila, 05071, Spain

Location

Investigational Site Number 724002

Barcelona, 08022, Spain

Location

Investigational Site Number 724008

Galdakao, 48960, Spain

Location

Investigational Site Number 724007

Lugo, 27004, Spain

Location

Investigational Site Number 724004

Madrid, 28805, Spain

Location

Investigational Site Number 724009

Pamplona, 31008, Spain

Location

Investigational Site Number 724005

Santa Coloma de Gramanet, 8923, Spain

Location

Investigational Site Number 724003

Seville, 41010, Spain

Location

Investigational Site Number 724006

Valencia, 46010, Spain

Location

Investigational Site Number 158004

Changhua County, Taiwan

Location

Investigational Site Number 158007

Kaohsiung Hsien,, Taiwan

Location

Investigational Site Number 158006

New Taipei City, Taiwan

Location

Investigational Site Number 158001

Taichung, 407, Taiwan

Location

Investigational Site Number 158009

Taichung, Taiwan

Location

Investigational Site Number 158005

Tainan, Taiwan

Location

Investigational Site Number 158002

Taipei, Taiwan

Location

Investigational Site Number 158003

Xindian District, 23137, Taiwan

Location

Investigational Site Number 792-013

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 792-009

Çanakkale, 17110, Turkey (Türkiye)

Location

Investigational Site Number 792-006

Diyarbakır, 21830, Turkey (Türkiye)

Location

Investigational Site Number 792-004

Istanbul, 34098, Turkey (Türkiye)

Location

Investigational Site Number 792-001

Izmir, 35340, Turkey (Türkiye)

Location

Investigational Site Number 792-016

Konya, Turkey (Türkiye)

Location

Investigational Site Number 792-007

Sivas, 58140, Turkey (Türkiye)

Location

Investigational Site Number 792-005

Trabzon, Turkey (Türkiye)

Location

Investigational Site Number 792-002

Van, 65080, Turkey (Türkiye)

Location

Investigational Site Number 784-001

Dubai, United Arab Emirates

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Glargine; insulin glulisine

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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2010
• First Posted: May 12, 2010
• Study Start: February 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: April 4, 2013

Record last verified: 2013-04

Locations

GR (10); KU (1); CN (12); CO (5); RO (3); TU (9); AE (1); BR (5); IN (7); KR (4); ME (5); ES (9); DK (3); TW (8); IT (10); AU (4)