Evaluation of Insulin Glargine in Combination With Sitagliptin in Type 2 Diabetes Patients: EASIE Extension Trial

Combination Therapy of Insulin Glargine and Sitagliptin in Patients With Type 2 Diabetes Not Adequately Controlled by a Previous Treatment With Metformin and Either Insulin Glargine or Sitagliptin

This study was the extension of the LANTU_C_02761 study named EASIE and identified as NCT00751114 (core study comparing insulin glargine versus sitagliptin in insulin-naïve patients treated with metformin and not adequately controlled).

All patients with Glycosylated Hemoglobin A1c (HbA1c) ≥ 7% at the end of the core study had the possibility to enter this extension study if they met the other inclusion criteria and did not present with any exclusion criteria.

The visit 14 of the core study (week 24) was the visit 1 (baseline, week 0) of the extension study which consisted of a 12-week treatment period.

The objectives of this extension study were:

• To assess the glycemic control (HbA1c <7%) of a 3-month combination therapy with metformin, insulin glargine and sitagliptin in patients not adequately controlled by a previous treatment with metformin plus either insulin glargine or sitagliptin.
• To assess the effect of insulin glargine in combination with sitagliptin on HbA1c level, fasting plasma glucose, 7-point glucose profile, hypoglycemia occurrence, body weight and overall safety.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin Glargine; Drug: Sitagliptin; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Sanofi-Aventis Administrative Office
• Brazil
  • Sao Paulo, Brazil
    • Sanofi-Aventis Administrative Office
• Colombia
  • Bogota, Colombia
    • Sanofi-Aventis Administrative Office
• Egypt
  • Cairo, Egypt
    • Sanofi-Aventis Administrative Office
• Greece
  • Kallithea, Greece
    • Sanofi-Aventis Administrative Office
• Hong Kong
  • Hong Kong, Hong Kong
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Israel
  • Natanya, Israel
    • Sanofi-Aventis Administrative Office
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Sanofi-Aventis Administrative Office
• Lebanon
  • Beirut, Lebanon
    • Sanofi-Aventis Administrative Office
• Mexico
  • Col. Coyoacan, Mexico
    • Sanofi-Aventis Administrative Office
• Netherlands
  • Gouda, Netherlands
    • Sanofi-Aventis Administrative Office
• Portugal
  • Porto Salvo, Portugal
    • Sanofi-Aventis Administrative Office
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis Administrative Office
• United Kingdom
  • Guildford Surrey, United Kingdom
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients who completed the core study LANTU_C_02761 (NCT00751114) i.e. went through the visit 14 investigation,
• HbA1c >= 7 %,
• Dose of metformin compliant with the inclusion criteria of the core study (i.e. at least 1 g/day), and maintained stable for the duration of the core study
• Ability and willingness to perform plasma blood glucose monitoring using the sponsor-provided plasma glucose meter and to complete the patient dairy,
• Signed informed consent obtained prior any study procedure,
• Willingness and ability to comply with the study protocol.

Exclusion Criteria:

• Treatment with oral antidiabetic drugs other than metformin and sitagliptin in the core study,
• Treatment with insulin other than Insulin Glargine in the core study (except in case of an emergency, for a period of time less than 7 days),
• Treatment with a non-permitted drug during the core study,
• Pregnant or lactating women,
• 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 in the core study),
• 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,
• 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),
• History of pancreatitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination insulin glargine and sitagliptin; Insulin glargine administered once a day, in the evening, at dinner or at bedtime. Starting dose: - last dose administered in the core study for patients previously treated with insulin glargine, - 0.2 U/Kg of body weight for patients previously treated with sitagliptin. Monitoring of blood glucose and titration: all patients, irrespective of their previous treatment group in the core study were empowered to adjust their insulin doses, under strict investigator's supervision. The goal was to achieve through a force titration 70 < Fasting Plasma Glucose (FPG) ≤ 100 mg/dL (3.9 <FPG ≤ 5.5 mmol/L). Sitagliptin: stable dose of 100 mg once a day administered with or without food.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HbA1c Response Rate: Percentage of Patients Achieving Glycosylated Haemoglobin A1c (HbA1c) < 7% at Study Endpoint (End of Treatment Period)	study endpoint: week 12 or earlier in case of premature discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c: Change From Baseline to Study Endpoint	Change = study endpoint - baseline	baseline, study endpoint: week 12 or earlier in case of premature discontinuation
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). Change = study endpoint - baseline.	baseline, study endpoint: week 12 or week 8 if value not available at week 12
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, study endpoint: week 12 or week 8 if value not available at week 12
Insulin Dose	Daily dose at the face-to-face visits	baseline, week 4, week 8, week 12
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 period (12 weeks) plus 7 days after last dose
Change in Body Weight From Baseline to Study Endpoint	Change = study endpoint - baseline	baseline, study endpoint: week 12 or week 8 or week 4 depending on last available value

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: February 25, 2009
• First Submitted That Met QC Criteria: February 25, 2009
• First Posted (Estimate): February 26, 2009

Study Record Updates

• Last Update Posted (Estimate): October 4, 2012
• Last Update Submitted That Met QC Criteria: September 3, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Insulin Glargine; Sitagliptin Phosphate
• Other Study ID Numbers: EXT_LANTU_C_02761; 2008-000521-19 (EudraCT Number)