Trial Outcomes & Findings for Evaluation of Insulin Glargine in Combination With Sitagliptin in Type 2 Diabetes Patients: EASIE Extension Trial (NCT NCT00851903)

NCT ID: NCT00851903

Last Updated: 2012-10-04

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 112 participants
• Primary outcome timeframe: study endpoint: week 12 or earlier in case of premature discontinuation
• Results posted on: 2012-10-04

Participant Flow

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.

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.

Participant milestones

Measure	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.
Overall Study STARTED	112
Overall Study Safety Population	112
Overall Study Treated by Combination	111
Overall Study Modified Intent-To-Treat Population	111
Overall Study COMPLETED	110
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure

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.

Overall Study Withdrawal by Subject

2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Combination Insulin Glargine and Sitagliptin n=111 Participants 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.
Age Continuous	52.4 years STANDARD_DEVIATION 9.3 • n=93 Participants
Sex: Female, Male Female	56 Participants n=93 Participants
Sex: Female, Male Male	55 Participants n=93 Participants
Body Weight	84.6 kg STANDARD_DEVIATION 21.0 • n=93 Participants
Body Mass Index	31.3 kg/m² STANDARD_DEVIATION 5.2 • n=93 Participants
Systolic Blood Pressure	129.9 mmHg STANDARD_DEVIATION 15.5 • n=93 Participants
Diastolic Blood Pressure	80.1 mmHg STANDARD_DEVIATION 7.3 • n=93 Participants
Heart Rate	76.9 beats/min STANDARD_DEVIATION 9.1 • n=93 Participants
Duration of diabetes	4.1 years INTER_QUARTILE_RANGE 5.1 • n=93 Participants
At least one diabetic late complication Yes	23 participants n=93 Participants
At least one diabetic late complication No	88 participants n=93 Participants
Glycosylated Hemoglobin A1c (HbA1c)	8.0 percent STANDARD_DEVIATION 1.0 • n=93 Participants
Fasting Plasma Glucose	151.5 mg/dL STANDARD_DEVIATION 46.9 • n=93 Participants
Self-Monitored Fasting Plasma Glucose	144.4 mg/dL STANDARD_DEVIATION 38.2 • n=93 Participants

PRIMARY outcome

Timeframe: study endpoint: week 12 or earlier in case of premature discontinuation

Population: The population analyzed consisted of the subset of mITT patients who had HbA1c value at study endpoint.

Outcome measures

Measure

Combination Insulin Glargine and Sitagliptin n=106 Participants 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.

HbA1c Response Rate: Percentage of Patients Achieving Glycosylated Haemoglobin A1c (HbA1c) < 7% at Study Endpoint (End of Treatment Period)

51.9 percentage of participants Interval 41.97 to 61.7

SECONDARY outcome

Timeframe: baseline, study endpoint: week 12 or earlier in case of premature discontinuation

Population: The population analyzed consisted of the subset of mITT patients who had both baseline and endpoint for this outcome measure

Change = study endpoint - baseline

Outcome measures

Measure

Combination Insulin Glargine and Sitagliptin n=106 Participants 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.

HbA1c: Change From Baseline to Study Endpoint

-0.80 percent Standard Deviation 1.05

SECONDARY outcome

Timeframe: baseline, study endpoint: week 12 or week 8 if value not available at week 12

Population: The population analyzed consisted of the subset of mITT patients who had both baseline and endpoint for this outcome measure

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.

Outcome measures

Measure

Combination Insulin Glargine and Sitagliptin n=104 Participants 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.

Self-Monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint

-35.43 mg/dL Standard Deviation 39.61

SECONDARY outcome

Timeframe: baseline, study endpoint: week 12 or week 8 if value not available at week 12

Population: 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.

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

Change = study endpoint - baseline.

Outcome measures

Measure	Combination Insulin Glargine and Sitagliptin n=104 Participants 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.
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint Before breakfast (N=104)	-34.2 mg/dL Standard Deviation 38.1
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint After breakfast (N=103)	-34.1 mg/dL Standard Deviation 48.1
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint Before lunch (N=104)	-26.6 mg/dL Standard Deviation 48.2
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint After lunch (N=104)	-26.5 mg/dL Standard Deviation 43.7
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint Before dinner (N=103)	-25.1 mg/dL Standard Deviation 43.0
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint After dinner (N=100)	-24.9 mg/dL Standard Deviation 46.7
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint At bedtime (N=93)	-35.2 mg/dL Standard Deviation 51.7

SECONDARY outcome

Timeframe: baseline, week 4, week 8, week 12

Population: mITT population

Daily dose at the face-to-face visits

Outcome measures

Measure	Combination Insulin Glargine and Sitagliptin n=111 Participants 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.
Insulin Dose Baseline	0.28 unit per kg body weight Standard Deviation 0.18
Insulin Dose Week 4 N=110	0.37 unit per kg body weight Standard Deviation 0.16
Insulin Dose Week 8 N=110	0.42 unit per kg body weight Standard Deviation 0.18
Insulin Dose Week 12	0.46 unit per kg body weight Standard Deviation 0.20

SECONDARY outcome

Timeframe: During the treatment period (12 weeks) plus 7 days after last dose

Population: The population analyzed for this outcome measure was the safety population

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]

Outcome measures

Measure

Combination Insulin Glargine and Sitagliptin n=112 Participants 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.

Number of Patients With at Least One Episode of Symptomatic Hypoglycemia

40 participants

SECONDARY outcome

Timeframe: baseline, study endpoint: week 12 or week 8 or week 4 depending on last available value

Population: The population analyzed was the safety population with both baseline and endpoint values available

Change = study endpoint - baseline

Outcome measures

Measure

Combination Insulin Glargine and Sitagliptin n=111 Participants 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.

Change in Body Weight From Baseline to Study Endpoint

1.15 kg Standard Deviation 2.24

Adverse Events

Combination Insulin Glargine and Sitagliptin

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Combination Insulin Glargine and Sitagliptin n=112 participants at risk 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.
Cardiac disorders Right ventricular failure	0.89% 1/112 • Adverse events were assessed throughout the extension study (12 weeks). Only adverse events starting from inclusion in the extension study were taken into account.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.89% 1/112 • Adverse events were assessed throughout the extension study (12 weeks). Only adverse events starting from inclusion in the extension study were taken into account.

Other adverse events

Adverse event data not reported

Additional Information

Trial Transparency Team

sanofi-aventis

Email: Contact-US@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER