Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-naive Patients

Diabetes Mellitus, Type 2 Clinical Trial

— EASIE  

Official title:

Superiority Study of Insulin Glargine Over Sitagliptin in Insulin-naïve Patients With Type 2 Diabetes Treated With Metformin and Not Adequately Controlled

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00751114
• Other study ID #: LANTU_C_02761
• Secondary ID: 2008-000516-32
• Status: Completed
• Phase: Phase 4
• First received: September 10, 2008
• Last updated: September 3, 2012
• Start date: November 2008
• Est. completion date: July 2011

Study information

• Verified date: September 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective was to demonstrate the superiority of insulin glargine over sitagliptin in reducing Glycosylated Hemoglobin A1c (HbA1c) from baseline to the end of the treatment period.

Secondary objective was to assess the effect of insulin glargine in comparison with sitagliptin on:

• HbA1c level

• Fasting Plasma Glucose (FPG)

• 7-point plasma glucose (PG) profiles

• Percentage of patients with HbA1c <7% and <6.5%

Safety objectives consisted of:

• Hypoglycemia occurrence

• Body weight

• Overall safety

Recruitment information / eligibility

• Status: Completed
• Enrollment: 515
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 70 Years

Eligibility

Inclusion Criteria:

• With type 2 diabetes diagnosed for at least 6 months,

• Not previously treated with insulin,

• On metformin for at least 3 months and a stable minimal dose of 1 g/day for at least 2 months

• HbA1c = 7 and < 11 %,

• Body Mass Index (BMI) between 25 and 45 kg/m² inclusively,

• Ability and willingness to perform plasma glucose (PG) monitoring using the Sponsor-provided PG meter and to complete the patient diary,

• Signed informed consent obtained prior any study procedures,

• Willingness and ability to comply with the study protocol.

Exclusion Criteria:

• Treatment with oral antidiabetic drugs other than metformin within the last 3 months,

• Previous treatment with the combination of metformin + sulfonylurea for more than 1 year,

• Previous treatment with Glucagon Like Peptide-1 (GLP-1) agonists or DiPeptidyl Peptidase (DPP) IV inhibitors,

• FPG (assessed by central laboratory measurement) = 280 mg/dL (15.4 mmol/L),

• Diabetes other than type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake...),

• Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method),

• In-patient care,

• Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study (an optic fundus examination should have been performed within the 2 years prior to study entry),

• Impaired renal function: serum creatinine = 1.5 mg/dL (= 133µmol/L) or = 1.4 mg/dL (= 124 µmol/L) in men and women, respectively,

• History of sensitivity to the study drugs or to drugs with a similar chemical structure,

• Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 3 x upper limit of normal range,

• Treatment with systemic corticosteroids within the 3 months prior to study entry or likelihood of requiring treatment during the study that are not permitted during the study (exception: in case of chronic adrenal insufficiency, systemic glucosteroids are accepted only if the disease is stable and the treatment dose stable for at least 3 months before study entry),

• Alcohol or drug abuse within the last year,

• Night shift worker,

• Presence of any condition (medical, psychological, social or geographical), current or anticipated that the investigator feels would compromise the patient's safety or limit the patient successful participation in the study,

• Treatment with weight loss medications (e.g. sibutramine, orlistat, rimonabant) within the last 3 months,

• Participation in another clinical trial within the month prior to visit 1,

• History of pancreatitis.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Insulin Glargine
Subcutaneous injection. 100 Units/mL solution for injection in a pre-filled SoloStar® pen (3 mL).
• Sitagliptin
Oral administration. 100 mg film-coated tablets.
• Metformin
Patients continued with metformin as usual oral anti-diabetic treatment.

Locations

Country	Name	City	State
Austria	Sanofi-Aventis Administrative Office	Vienna
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Colombia	Sanofi-Aventis Administrative Office	Bogota
Egypt	Sanofi-Aventis Administrative Office	Cairo
Greece	Sanofi-Aventis Administrative Office	Kallithea
Hong Kong	Sanofi-Aventis Administrative Office	Hong Kong
India	Sanofi-Aventis Administrative Office	Mumbai
Israel	Sanofi-Aventis Administrative Office	Natanya
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Lebanon	Sanofi-Aventis Administrative Office	Beirut
Mexico	Sanofi-Aventis Administrative Office	Col. Coyoacan
Netherlands	Sanofi-Aventis Administrative Office	Gouda
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Spain	Sanofi-Aventis Administrative Office	Barcelona
Turkey	Sanofi-Aventis Administrative Office	Istanbul
United Kingdom	Sanofi-Aventis Administrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  Colombia,  Egypt,  Greece,  Hong Kong,  India,  Israel,  Korea, Republic of,  Lebanon,  Mexico,  Netherlands,  Portugal,  Spain,  Turkey,  United Kingdom, 

References & Publications (1)

Aschner P, Chan J, Owens DR, Picard S, Wang E, Dain MP, Pilorget V, Echtay A, Fonseca V; EASIE investigators. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, ran — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c: Change From Baseline to Study Endpoint	Change in HbA1c from baseline to study endpoint defined as the last available HbA1c value measured during the 24-week treatment period.	baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14	No
Secondary	HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 7% at Study Endpoint		study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14	No
Secondary	HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 6.5% at Study Endpoint		study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14	No
Secondary	Self-monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint	SMFPG mean = mean of the fasting plasma glucose values recorded on the 6 consecutive days before the visit (at least 3 values needed).; Study endpoint was defined as the last available SMFPG mean value collected on-treatment.; Change= study endpoint - baseline	baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value	No
Secondary	7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint	7-point plasma glucose recorded before and after breakfast, before and after lunch, before and after dinner and at bedtime.; Change = study endpoint - baseline.	baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14	No
Secondary	Insulin Dose in the Insulin Glargine Group	Daily dose at the face-to-face visits.	visit 4 (week 2), visit 8 (week 6), visit 11 (week 12), visit 12 (week 16), visit 14 (week 24), first dose received defined as first available value, study endpoint defined as last available value	No
Secondary	Lipid Profile: Change From Baseline to Study Endpoint		baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14	No
Secondary	Change in Body Weight From Baseline to Study Endpoint		baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value	Yes
Secondary	Number of Patients With at Least One Episode of Symptomatic Hypoglycemia	Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia confirmed or not by a plasma glucose measurement <= 70mg/dL [3.9 mmol/L]	During the treatment phase (24 weeks) plus 7 days after last dose	Yes
Secondary	Number of Patients With at Least One Episode of Severe Symptomatic Hypoglycemia	Severe symptomatic hypoglycemia was defined as an event with clinical symptoms which required assistance of another person and with either a Plasma Glucose level < 36 mg/dL (2 mmol/L) or with a prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration	During the treatment phase (24 weeks) plus 7 days after last dose	Yes