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6-month Comparison of Morning Lantus Versus Neutral Protamine Hagedorn Insulin in Young Children With Type 1 Diabetes (PRESCHOOL)

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ClinicalTrials.gov Identifier: NCT00993473
Recruitment Status : Completed
First Posted : October 12, 2009
Results First Posted : June 22, 2012
Last Update Posted : June 27, 2012
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: Insulin glargine (HOE901)
Drug: Neutral Protamine Hagedorn (NPH) insulin
Drug: Insulin lispro
Enrollment 125
Recruitment Details The study was conducted in 61 centers (72 were initiated) in 16 countries between October 15, 2009 and March 30, 2011.
Pre-assignment Details A total of 165 patients were screened and 125 were randomized. Forty patients (24.2%) failed the screening selection process, mainly due to noncompliance with the study required Continuous Glucose Monitoring (CGM) performance and other procedures.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Period Title: Overall Study
Started 61 [1] 64 [2]
Completed 57 54
Not Completed 4 10
Reason Not Completed
Adverse Event             0             2
Protocol Violation             1             2
Lost to Follow-up             1             0
Withdrawal by Subject             1             5
Technical problem with CGM device             0             1
Family event             1             0
[1]
61 patients randomized to Lantus but 62 patients treated with Lantus due to a dispensation's error
[2]
64 patients randomized to NPH but only 63 patients treated with NPH due to a dispensation's error
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin Total
Hide Arm/Group Description

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Total of all reporting groups
Overall Number of Baseline Participants 61 64 125
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants 64 participants 125 participants
4.3  (0.9) 4.1  (1.0) 4.2  (1.0)
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 61 participants 64 participants 125 participants
5.0
(2 to 5)
4.0
(1 to 6)
4.0
(1 to 6)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
<= 3 years 10 17 27
> 3 years 51 47 98
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Male 32 30 62
Female 29 34 63
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Caucasian/White 53 48 101
Black 2 2 4
Asian/Oriental 4 11 15
Other 2 3 5
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Hispanic 17 13 30
Non Hispanic 44 51 95
Duration of diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants 64 participants 125 participants
2.12  (1.16) 2.12  (1.01) 2.12  (1.08)
Duration of diabetes  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 61 participants 64 participants 125 participants
1.63
(1.0 to 5.3)
2.05
(1.0 to 4.9)
1.81
(1.0 to 5.3)
Treated by bolus insulin at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Yes 54 58 112
No 7 6 13
Treated by basal insulin at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Yes 58 57 115
No 3 7 10
Treated by mixed (bolus & basal) insulin at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Yes 5 8 13
No 56 56 112
Number of daily basal insulin injections at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
1 32 41 73
2 21 15 36
>=3 5 1 6
Not treated with basal insulin at baseline 3 7 10
Total daily dose of basal insulin injection at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Analyzed 57 57 114
Not treated by basal insulin or missing 4 7 11
Total daily dose of basal insulin injection at baseline  
Mean (Standard Deviation)
Unit of measure:  International Units
Number Analyzed 61 participants 64 participants 125 participants
7.29  (4.11) 7.61  (4.77) 7.45  (4.43)
Total daily dose of basal insulin injection at baseline  
Median (Full Range)
Unit of measure:  International Units
Number Analyzed 61 participants 64 participants 125 participants
6.00
(2.0 to 24.0)
6.00
(1.5 to 24.0)
6.00
(1.5 to 24.0)
Total daily dose of bolus insulin injection at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 64 participants 125 participants
Analyzed 52 57 109
Not treated by bolus insulin or missing 9 7 16
Total daily dose of bolus insulin injection at baseline  
Mean (Standard Deviation)
Unit of measure:  International Units
Number Analyzed 61 participants 64 participants 125 participants
7.14  (3.64) 7.98  (7.20) 7.58  (5.77)
Total daily dose of bolus insulin injection at baseline  
Median (Full Range)
Unit of measure:  International Units
Number Analyzed 61 participants 64 participants 125 participants
7.75
(1.3 to 16.0)
7.00
(0.8 to 45.0)
7.00
(0.8 to 45.0)
1.Primary Outcome
Title Event Rate of "All Hypoglycemia" Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year)
Hide Description The rate of "all hypoglycemia" was calculated from "all hypoglycemia" episodes which occurred during the 24-week on-treatment period and consisted of: - symptomatic hypoglycemia episodes validated by the study investigator based on entries in patients' diaries, - low continuous glucose monitoring system (CGMS) excursions (interstitial glucose <70 mg/dL [3.9 mmol/L]) confirmed by fingerstick blood glucose (FSBG) <70 mg/dL, - low FSBG readings (values <70 mg/dL) performed at other times.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized patients who received at least one dose of the study medication (modified intent-to-treat [mITT] population). For efficacy analyses, patients were analyzed in the treatment group allocated by the Interactive Voice Response System (IVRS) at randomization (as randomized).
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: number of events per patient-year
192.75  (119.28) 168.91  (101.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lantus (Insulin Glargine), NPH Insulin
Comments The sample size was calculated to ensure sufficient power so that the upper bound of the 2-sided 95% CI for the Lantus /NPH ratio would not exceed 1.15 based on an expected overall rate of „all hypoglycemia“ of 80 events per patient-year of exposure to NPH insulin and to Lantus. It was planned to randomize at least 45 and up to approximately 60 patients in each of the 2 treatment groups so that at least 70 patients would complete the 24 weeks of treatment.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Noninferiority would be demonstrated if the upper bound of the 95% confidence interval (CI) for the ratio of the rate of “all hypoglycemia” in the Lantus group to the rate in the NPH group was <1.15. Superiority would be demonstrated if the upper bound of the 95% CI was <1. The margin for noninferiority corresponded to one-half of the 30% difference in hypoglycemia event rate considered as a clinically significant difference by American Diabetes Association 2005 Working Group on Hypoglycemia.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Generalized Linear Model
Comments A stepwise closed testing approach was used for the primary “all hypoglycemia” outcome analysis to assess noninferiority and superiority sequentially.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.97 to 1.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Risk ratio between treatment groups (Lantus/NPH) estimated by Generalized Linear Model with fixed effect terms for randomization strata and treatment.
2.Secondary Outcome
Title Event Rate of Symptomatic Hypoglycemia (Individual Component of Primary Endpoint) Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year)
Hide Description Symptomatic hypoglycemia: any event with clinical symptoms considered to result from hypoglycemia, validated by the study investigator based on data from patient diaries.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: events per patient-year
25.54  (37.25) 33.02  (47.95)
3.Secondary Outcome
Title Event Rate of Severe Symptomatic Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years
Hide Description Severe symptomatic hypoglycemia: any event with clinical symptoms considered to result from a hypoglycemic episode for which the patients required the assistance of a third party (ie, other than the patient, or a parent/usual caregiver; eg, from emergency personnel), because the patients/parents could not treat the event with acute neurological impairment directly resulting from the hypoglycemic event. The occurrence of seizure, coma, unconsciousness, or the use of glucagon, were also to qualify a hypoglycemic episode as severe.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Overall Number of Units Analyzed
Type of Units Analyzed: Episodes
4 2
Mean (Standard Deviation)
Unit of Measure: number of events per patient-year
0.14  (0.55) 0.07  (0.38)
4.Secondary Outcome
Title Event Rate of Nocturnal Hypoglycemia Defined as the Total Number of "All Hypoglycemia" Episodes Divided by the Total Duration of the On-treatment Period in Years
Hide Description Nocturnal hypoglycemia: any event from the “all hypoglycemia” total that occurred between 23:00 and 07:00 hours.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: number of events per patient-year
33.50  (25.62) 30.92  (24.97)
5.Secondary Outcome
Title Event Rate of Nocturnal Symptomatic Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years
Hide Description Nocturnal symptomatic hypoglycemia: any symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: number of events per patient-year
2.38  (5.42) 3.65  (6.75)
6.Secondary Outcome
Title Event Rate of Severe Nocturnal Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years
Hide Description Severe nocturnal symptomatic hypoglycemia: any severe symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Overall Number of Units Analyzed
Type of Units Analyzed: Episodes
1 0
Mean (Standard Deviation)
Unit of Measure: number of events per patient-year
0.04  (0.29) 0.00  (0.00)
7.Secondary Outcome
Title Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment
Hide Description [Not Specified]
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population. However post-baseline HbA1c values were missing for 9 patients: 2 patients in the Lantus group and 7 in the NPH group.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: percent HbA1c
Baseline HbA1c 8.023  (1.049) 8.248  (1.429)
End of treatment HbA1c (N = 59 & 57) 8.071  (0.884) 8.344  (1.161)
Absolute change from baseline (N = 59 & 57) 0.036  (0.979) 0.000  (1.035)
8.Secondary Outcome
Title Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)
Hide Description Assessed using an analysis of covariance (ANCOVA) model with treatment, and randomization strata (baseline number of CGM hypoglycemic excursions <0.5 events/24hours or ≥0.5 events/24 hours, and baseline HbA1c <8.5% or ≥8.5%) as fixed effects, and using the baseline value as covariate.
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Least Squares Mean (Standard Error)
Unit of Measure: percent HbA1c
End of treatment HbA1c (ANCOVA) 8.139  (0.1065) 8.232  (0.1134)
Absolute change from baseline HbA1c (ANCOVA) -0.048  (0.1065) 0.045  (0.1134)
9.Secondary Outcome
Title Percentage of Patients Reaching HbA1c Target of Less Than 7.5% at the End of Treatment Visit
Hide Description Percentage of patients reaching International Society for Pediatric and Adolescent Diabetes (ISPAD)-recommended goals of Glycosylated Hemoglobin A1c <7.5% at the end of treatment visit.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed consisted of patients from the mITT population (as defined for primary outcome measure) with post-baseline HbA1c values. 2 patients from the Lantus group and 7 from the NPH group had no post-baseline HbA1c value.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 59 57
Measure Type: Number
Unit of Measure: percentage of participants
22.0 22.8
10.Secondary Outcome
Title Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment
Hide Description [Not Specified]
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population. However 1 patient in the NPH group did not have baseline CGM value and 2 other patients (1 in the Lantus group and 1 in the NPH group) did not have on-treatment CGM values.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline daily BG (N= 61 & 63) 11.263  (1.887) 11.170  (1.986)
End of treatment daily BG (N= 60 & 63) 11.085  (2.077) 11.712  (2.166)
Absolute change from baseline (N= 60 & 62) -0.218  (2.399) 0.501  (1.906)
11.Other Pre-specified Outcome
Title Number of Patients With Different Types of Hypoglycemia Events
Hide Description Definitions of the different types of hypoglycemia events provided in the outcome measure description of the corresponding event rates.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Measure Type: Number
Unit of Measure: participants
Patients with "All hypoglycemia" 61 63
Patients with symptomatic hypoglycemia 40 44
Patients with severe symptomatic hypoglycemia 4 2
Patients with nocturnal hypoglycemia 59 60
Patients with nocturnal symptomatic hypoglycemia 17 28
Patients with severe noct. sympto. hypoglycemia 1 0
Patients with "All confirmed low CGMS excursions" 60 61
Patients with "All confirmed low FSBG" 61 63
12.Other Pre-specified Outcome
Title Percent of Blood Glucose (BG) Within the Range of 70 – 180 mg/dL (3.9-10 mmol/L)
Hide Description Calculated for each patient as the percent of all on-treatment CGMS values falling within the range of 70 – 180 mg/dL (3.9 – 10 mmol/L) inclusive.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed consisted of patients from the mITT population (as defined for primary outcome measure) with on-treatment CGM values (1 patient from the Lantus group and 1 from the NPH group did not have on-treatment CGM).
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 60 63
Mean (Standard Deviation)
Unit of Measure: percent of CGMS values within the range
41.667  (12.048) 38.158  (10.908)
13.Other Pre-specified Outcome
Title Blood Glucose Variability Based on All On-treatment CGMS Values
Hide Description Calculated for any given patient as the standard deviation (SD) of all CGMS interstitial glucose values recorded over all CGMS placements.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed consisted of patients from the mITT population (as defined for primary outcome measure) with on-treatment CGM values (1 patient from the Lantus group and 1 from the NPH group did not have on-treatment CGM).
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 60 63
Mean (Standard Deviation)
Unit of Measure: mmol/L
4.954  (0.826) 5.089  (0.731)
14.Other Pre-specified Outcome
Title Nocturnal Blood Glucose Variability Based on All On-treatment CGMS Values
Hide Description Calculated for any given patient as the standard deviation (SD) of all CGMS interstitial glucose values recorded during the nocturnal time period (between 23:00 and 07:00 hours).
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed consisted of patients from the mITT population (as defined for primary outcome measure) with on-treatment CGM values (1 patient from the Lantus group and 1 from the NPH group did not have on-treatment CGM).
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 60 63
Mean (Standard Deviation)
Unit of Measure: mmol/L
4.747  (0.973) 4.837  (0.825)
15.Post-Hoc Outcome
Title Event Rate of "All Confirmed Low CGMS Excursions" (Individual Component of Primary Endpoint) Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year)
Hide Description "All confirmed low CGMS excursions" consisted of all low continuous glucose monitoring system (CGMS) excursions (interstitial glucose <70 mg/dL [3.9 mmol/L]) confirmed by fingerstick blood glucose (FSBG) <70 mg/dL.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: events per patient-year
74.61  (74.09) 71.60  (53.20)
16.Post-Hoc Outcome
Title Event Rate of "All Confirmed Low FSBG" (Individual Component of the Primary Endpoint) Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year)
Hide Description "All confirmed low FSBG" consisted of all low FSBG readings (values <70 mg/dL) performed at other times.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as for primary endpoint: mITT population.
Arm/Group Title Lantus (Insulin Glargine) NPH Insulin
Hide Arm/Group Description:

Lantus (insulin glargine) given as basal insulin once a day in the morning by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Neutral Protamine Hagedorn (NPH) human insulin given as basal insulin either once or twice per day by subcutaneous injection.

Dose: titrated to achieve glycemic targets as described in protocol section.

Overall Number of Participants Analyzed 61 64
Mean (Standard Deviation)
Unit of Measure: events per patient-year
192.69  (121.78) 168.24  (101.21)
Time Frame Adverse events were monitored from baseline to 7 days after last treatment visit.
Adverse Event Reporting Description The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
 
Arm/Group Title Lantus NPH Insulin
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Lantus NPH Insulin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lantus NPH Insulin
Affected / at Risk (%) Affected / at Risk (%)
Total   8/62 (12.90%)   2/63 (3.17%) 
Gastrointestinal disorders     
Gastritis * 1  2/62 (3.23%)  0/63 (0.00%) 
Abdominal pain * 1  1/62 (1.61%)  0/63 (0.00%) 
Infections and infestations     
Viral infection * 1  1/62 (1.61%)  0/63 (0.00%) 
Lower respiratory tract infection * 1  0/62 (0.00%)  1/63 (1.59%) 
Metabolism and nutrition disorders     
Hypoglycaemic seizure * 1  2/62 (3.23%)  0/63 (0.00%) 
Dehydration * 1  1/62 (1.61%)  0/63 (0.00%) 
Diabetic ketoacidosis * 1  1/62 (1.61%)  1/63 (1.59%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lantus NPH Insulin
Affected / at Risk (%) Affected / at Risk (%)
Total   30/62 (48.39%)   33/63 (52.38%) 
Gastrointestinal disorders     
Vomiting * 1  5/62 (8.06%)  4/63 (6.35%) 
General disorders     
Device lead damage * 1  5/62 (8.06%)  2/63 (3.17%) 
Pyrexia * 1  3/62 (4.84%)  7/63 (11.11%) 
Infections and infestations     
Gastroenteritis * 1  6/62 (9.68%)  6/63 (9.52%) 
Nasopharyngitis * 1  6/62 (9.68%)  5/63 (7.94%) 
Pharyngitis * 1  6/62 (9.68%)  2/63 (3.17%) 
Upper respiratory tract infection * 1  4/62 (6.45%)  6/63 (9.52%) 
Bronchitis * 1  3/62 (4.84%)  5/63 (7.94%) 
Otitis media * 1  1/62 (1.61%)  4/63 (6.35%) 
Tonsillitis * 1  1/62 (1.61%)  4/63 (6.35%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  2/62 (3.23%)  4/63 (6.35%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
There are numerous potential biases that could affect the timing and frequency of performance of sporadic FSBG, such as mealtime dosing and choice of bolus insulin dose, stability and familiarity with insulin regimens, and parental anxiety levels.
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 30 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
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00993473     History of Changes
Other Study ID Numbers: EFC11202
2009-011231-12 ( EudraCT Number )
First Submitted: October 9, 2009
First Posted: October 12, 2009
Results First Submitted: March 28, 2012
Results First Posted: June 22, 2012
Last Update Posted: June 27, 2012