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

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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:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Insulin Glargine
Drug: Sitagliptin
Drug: Metformin
Enrollment 112
Recruitment Details Among the 445 patients who completed the EASIE study, 194 had an endpoint Glycosylated Hemoglobin A1c (HbA1c) ≥ 7%. A total of 112 patients were included in the extension study: 37 uncontrolled on previous treatment with metformin and insulin glargine and 75 uncontrolled on previous treatment with metformin and sitagliptin in the EASIE study.
Pre-assignment Details Among the 112 included patients, two patients prematurely discontinued from the study. One of them had continued his sitagliptin treatment but never started the insulin glargine treatment.
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description

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.

Period Title: Overall Study
Started 112
Safety Population 112 [1]
Treated by Combination 111 [2]
Modified Intent-To-Treat Population 111 [3]
Completed 110
Not Completed 2
Reason Not Completed
Withdrawal by Subject             2
[1]
patients treated with at least one dose of insulin glargine OR one dose of sitagliptin
[2]
patients treated with at least one dose of insulin glargine AND one dose of sitagliptin
[3]
mITT population: patients treated by combination with at least 1 on-treatment efficacy measure
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description

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 <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.

Overall Number of Baseline Participants 111
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants
52.4  (9.3)
[1]
Measure Description:

mITT population

Age collected at EASIE study entry (24 weeks before baseline)

Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
Female
56
  50.5%
Male
55
  49.5%
[1]
Measure Description: mITT population
Body Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 111 participants
84.6  (21.0)
[1]
Measure Description: mITT population
Body Mass Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m²
Number Analyzed 111 participants
31.3  (5.2)
[1]
Measure Description: mITT population
Systolic Blood Pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 111 participants
129.9  (15.5)
[1]
Measure Description: mITT population
Diastolic Blood Pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 111 participants
80.1  (7.3)
[1]
Measure Description: mITT population
Heart Rate   [1] 
Mean (Standard Deviation)
Unit of measure:  Beats/min
Number Analyzed 111 participants
76.9  (9.1)
[1]
Measure Description: mITT population
Duration of diabetes   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 111 participants
4.1
(2.0 to 8.3)
[1]
Measure Description:

mITT population

Duration of diabetes collected at EASIE study entry (24 weeks before baseline)

At least one diabetic late complication   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 111 participants
Yes 23
No 88
[1]
Measure Description:

mITT population

Diabetic late complications: myocardial infarction, angina pectoris, coronary artery disease, heart failure, stroke, transient ischemic attack, peripheral vascular disease, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy

Information collected at EASIE study entry (24 weeks before baseline)

Glycosylated Hemoglobin A1c (HbA1c)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 111 participants
8.0  (1.0)
[1]
Measure Description: mITT population
Fasting Plasma Glucose   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 111 participants
151.5  (46.9)
[1]
Measure Description: mITT population but due to missing values N=110
Self-Monitored Fasting Plasma Glucose   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 111 participants
144.4  (38.2)
[1]
Measure Description: mITT population but due to missing values N=104
1.Primary Outcome
Title HbA1c Response Rate: Percentage of Patients Achieving Glycosylated Haemoglobin A1c (HbA1c) < 7% at Study Endpoint (End of Treatment Period)
Hide Description [Not Specified]
Time Frame study endpoint: week 12 or earlier in case of premature discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed consisted of the subset of mITT patients who had HbA1c value at study endpoint.
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description:

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 <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.

Overall Number of Participants Analyzed 106
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
51.9
(41.97 to 61.70)
2.Secondary Outcome
Title HbA1c: Change From Baseline to Study Endpoint
Hide Description Change = study endpoint - baseline
Time Frame baseline, study endpoint: week 12 or earlier in case of premature discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed consisted of the subset of mITT patients who had both baseline and endpoint for this outcome measure
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description:

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 <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.

Overall Number of Participants Analyzed 106
Mean (Standard Deviation)
Unit of Measure: percent
-0.80  (1.05)
3.Secondary Outcome
Title Self-Monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint
Hide Description

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.

Time Frame baseline, study endpoint: week 12 or week 8 if value not available at week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed consisted of the subset of mITT patients who had both baseline and endpoint for this outcome measure
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description:

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 <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.

Overall Number of Participants Analyzed 104
Mean (Standard Deviation)
Unit of Measure: mg/dL
-35.43  (39.61)
4.Secondary Outcome
Title 7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint
Hide Description

7-point plasma glucose recorded before and after breakfast, before and after lunch, before and after dinner and at bedtime.

Change = study endpoint - baseline.

Time Frame baseline, study endpoint: week 12 or week 8 if value not available at week 12
Hide Outcome Measure Data
Hide Analysis Population Description

The population analyzed consisted of the subset of mITT patients who had valid 7-point plasma glucose profiles (4 points needed for a valid profile) both at baseline and endpoint.

Depending on the time point, few values were missing.

Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description:

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 <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.

Overall Number of Participants Analyzed 104
Mean (Standard Deviation)
Unit of Measure: mg/dL
Before breakfast (N=104) -34.2  (38.1)
After breakfast (N=103) -34.1  (48.1)
Before lunch (N=104) -26.6  (48.2)
After lunch (N=104) -26.5  (43.7)
Before dinner (N=103) -25.1  (43.0)
After dinner (N=100) -24.9  (46.7)
At bedtime (N=93) -35.2  (51.7)
5.Secondary Outcome
Title Insulin Dose
Hide Description Daily dose at the face-to-face visits
Time Frame baseline, week 4, week 8, week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description:

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 <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.

Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: unit per kg body weight
Baseline 0.28  (0.18)
Week 4 N=110 0.37  (0.16)
Week 8 N=110 0.42  (0.18)
Week 12 0.46  (0.20)
6.Secondary Outcome
Title Number of Patients With at Least One Episode of Symptomatic Hypoglycemia
Hide Description 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]
Time Frame During the treatment period (12 weeks) plus 7 days after last dose
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed for this outcome measure was the safety population
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description:

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 <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.

Overall Number of Participants Analyzed 112
Measure Type: Number
Unit of Measure: participants
40
7.Secondary Outcome
Title Change in Body Weight From Baseline to Study Endpoint
Hide Description Change = study endpoint - baseline
Time Frame baseline, study endpoint: week 12 or week 8 or week 4 depending on last available value
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed was the safety population with both baseline and endpoint values available
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description:

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 <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.

Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: kg
1.15  (2.24)
Time Frame Adverse events were assessed throughout the extension study (12 weeks). Only adverse events starting from inclusion in the extension study were taken into account.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Combination Insulin Glargine and Sitagliptin
Hide Arm/Group Description

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 <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.

All-Cause Mortality
Combination Insulin Glargine and Sitagliptin
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Combination Insulin Glargine and Sitagliptin
Affected / at Risk (%)
Total   2/112 (1.79%) 
Cardiac disorders   
Right ventricular failure * 1  1/112 (0.89%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Endometrial cancer * 1  1/112 (0.89%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDra
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combination Insulin Glargine and Sitagliptin
Affected / at Risk (%)
Total   0/112 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 45 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00851903     History of Changes
Other Study ID Numbers: EXT_LANTU_C_02761
2008-000521-19 ( EudraCT Number )
First Submitted: February 25, 2009
First Posted: February 26, 2009
Results First Submitted: September 3, 2012
Results First Posted: October 4, 2012
Last Update Posted: October 4, 2012