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

• ClinicalTrials.gov Identifier: NCT00851903
• Recruitment Status: Completed
• First Posted: February 26, 2009
• Results First Posted: October 4, 2012
• Last Update Posted: October 4, 2012
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: February 25, 2009
• First Posted Date: February 26, 2009
• Results First Submitted Date: September 3, 2012
• Results First Posted Date: October 4, 2012
• Last Update Posted Date: October 4, 2012
• Study Start Date: June 2009
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 3, 2012): HbA1c Response Rate: Percentage of Patients Achieving Glycosylated Haemoglobin A1c (HbA1c) < 7% at Study Endpoint (End of Treatment Period) [ Time Frame: study endpoint: week 12 or earlier in case of premature discontinuation ]
• Original Primary Outcome Measures (submitted: February 25, 2009): Patients achieving glycosylated haemoglobin (HbA1c) < 7% [ Time Frame: At study endpoint ]

Current Secondary Outcome Measures (submitted: September 3, 2012)

• HbA1c: Change From Baseline to Study Endpoint [ Time Frame: baseline, study endpoint: week 12 or earlier in case of premature discontinuation ]
  Change = study endpoint - baseline
• Self-Monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint [ Time Frame: baseline, study endpoint: week 12 or week 8 if value not available at week 12 ]
  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.
• 7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint [ Time Frame: baseline, study endpoint: week 12 or week 8 if value not available at week 12 ]
  7-point plasma glucose recorded before and after breakfast, before and after lunch, before and after dinner and at bedtime. Change = study endpoint - baseline.
• Insulin Dose [ Time Frame: baseline, week 4, week 8, week 12 ]
  Daily dose at the face-to-face visits
• Number of Patients With at Least One Episode of Symptomatic Hypoglycemia [ Time Frame: During the treatment period (12 weeks) plus 7 days after last dose ]
  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]
• Change in Body Weight From Baseline to Study Endpoint [ Time Frame: baseline, study endpoint: week 12 or week 8 or week 4 depending on last available value ]
  Change = study endpoint - baseline

Original Secondary Outcome Measures (submitted: February 25, 2009)

• HbA1c [ Time Frame: At baseline and week 12 ]
• Self-monitored Fasting Plasma Glucose (FPG) [ Time Frame: At baseline, weeks 8 and 12. ]
• Plasma glucose profile (7-point 24h profile) [ Time Frame: At baseline, weeks 8 and 12. ]
• Hypoglycemia occurrence [ Time Frame: From the baseline to the end of treatment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

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

Study Arms

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.

Interventions:

• Drug: Insulin Glargine
• Drug: Sitagliptin
• Drug: Metformin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 20, 2011): 112
• Original Estimated Enrollment (submitted: February 25, 2009): 530
• Actual Study Completion Date: September 2011
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 Years to 71 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Brazil, Colombia, Egypt, Greece, Hong Kong, India, Israel, Korea, Republic of, Lebanon, Mexico, Netherlands, Portugal, Spain, United Kingdom, United States
• Removed Location Countries: Turkey

Administrative Information

• NCT Number: NCT00851903
• Other Study ID Numbers: EXT_LANTU_C_02761; 2008-000521-19 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Sanofi
• Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: September 2012