Trial Outcomes & Findings for 6-month Comparison of Morning Lantus Versus Neutral Protamine Hagedorn Insulin in Young Children With Type 1 Diabetes (NCT NCT00993473)
NCT ID: NCT00993473
Last Updated: 2012-06-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
125 participants
Primary outcome timeframe
6 months
Results posted on
2012-06-27
Participant Flow
The study was conducted in 61 centers (72 were initiated) in 16 countries between October 15, 2009 and March 30, 2011.
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.
Participant milestones
| Measure |
Lantus (Insulin Glargine)
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.
|
NPH Insulin
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 Study
STARTED
|
61
|
64
|
|
Overall Study
COMPLETED
|
57
|
54
|
|
Overall Study
NOT COMPLETED
|
4
|
10
|
Reasons for withdrawal
| Measure |
Lantus (Insulin Glargine)
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.
|
NPH Insulin
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 Study
Adverse Event
|
0
|
2
|
|
Overall Study
Protocol Violation
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
5
|
|
Overall Study
Technical problem with CGM device
|
0
|
1
|
|
Overall Study
Family event
|
1
|
0
|
Baseline Characteristics
6-month Comparison of Morning Lantus Versus Neutral Protamine Hagedorn Insulin in Young Children With Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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
n=125 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
5.0 years
n=5 Participants
|
4.0 years
n=7 Participants
|
4.0 years
n=5 Participants
|
|
Age, Customized
<= 3 years
|
10 participants
n=5 Participants
|
17 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Age, Customized
> 3 years
|
51 participants
n=5 Participants
|
47 participants
n=7 Participants
|
98 participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
32 participants
n=5 Participants
|
30 participants
n=7 Participants
|
62 participants
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
29 participants
n=5 Participants
|
34 participants
n=7 Participants
|
63 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian/White
|
53 participants
n=5 Participants
|
48 participants
n=7 Participants
|
101 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian/Oriental
|
4 participants
n=5 Participants
|
11 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
17 participants
n=5 Participants
|
13 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non Hispanic
|
44 participants
n=5 Participants
|
51 participants
n=7 Participants
|
95 participants
n=5 Participants
|
|
Duration of diabetes
|
1.63 years
n=5 Participants
|
2.05 years
n=7 Participants
|
1.81 years
n=5 Participants
|
|
Treated by bolus insulin at baseline
Yes
|
54 participants
n=5 Participants
|
58 participants
n=7 Participants
|
112 participants
n=5 Participants
|
|
Treated by bolus insulin at baseline
No
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Treated by basal insulin at baseline
Yes
|
58 participants
n=5 Participants
|
57 participants
n=7 Participants
|
115 participants
n=5 Participants
|
|
Treated by basal insulin at baseline
No
|
3 participants
n=5 Participants
|
7 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Treated by mixed (bolus & basal) insulin at baseline
Yes
|
5 participants
n=5 Participants
|
8 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Treated by mixed (bolus & basal) insulin at baseline
No
|
56 participants
n=5 Participants
|
56 participants
n=7 Participants
|
112 participants
n=5 Participants
|
|
Number of daily basal insulin injections at baseline
1
|
32 participants
n=5 Participants
|
41 participants
n=7 Participants
|
73 participants
n=5 Participants
|
|
Number of daily basal insulin injections at baseline
2
|
21 participants
n=5 Participants
|
15 participants
n=7 Participants
|
36 participants
n=5 Participants
|
|
Number of daily basal insulin injections at baseline
>=3
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Number of daily basal insulin injections at baseline
Not treated with basal insulin at baseline
|
3 participants
n=5 Participants
|
7 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Total daily dose of basal insulin injection at baseline
Analyzed
|
57 participants
n=5 Participants
|
57 participants
n=7 Participants
|
114 participants
n=5 Participants
|
|
Total daily dose of basal insulin injection at baseline
Not treated by basal insulin or missing
|
4 participants
n=5 Participants
|
7 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Total daily dose of basal insulin injection at baseline
|
6.00 International Units
n=5 Participants
|
6.00 International Units
n=7 Participants
|
6.00 International Units
n=5 Participants
|
|
Total daily dose of bolus insulin injection at baseline
Analyzed
|
52 participants
n=5 Participants
|
57 participants
n=7 Participants
|
109 participants
n=5 Participants
|
|
Total daily dose of bolus insulin injection at baseline
Not treated by bolus insulin or missing
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Total daily dose of bolus insulin injection at baseline
|
7.75 International Units
n=5 Participants
|
7.00 International Units
n=7 Participants
|
7.00 International Units
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: 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).
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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
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)
|
192.75 number of events per patient-year
Standard Deviation 119.28
|
168.91 number of events per patient-year
Standard Deviation 101.04
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
Symptomatic hypoglycemia: any event with clinical symptoms considered to result from hypoglycemia, validated by the study investigator based on data from patient diaries.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
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)
|
25.54 events per patient-year
Standard Deviation 37.25
|
33.02 events per patient-year
Standard Deviation 47.95
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=4 Episodes
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.
|
NPH Insulin
n=2 Episodes
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.
|
|---|---|---|
|
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
|
0.14 number of events per patient-year
Standard Deviation 0.55
|
0.07 number of events per patient-year
Standard Deviation 0.38
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
Nocturnal hypoglycemia: any event from the "all hypoglycemia" total that occurred between 23:00 and 07:00 hours.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
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
|
33.50 number of events per patient-year
Standard Deviation 25.62
|
30.92 number of events per patient-year
Standard Deviation 24.97
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
Nocturnal symptomatic hypoglycemia: any symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
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
|
2.38 number of events per patient-year
Standard Deviation 5.42
|
3.65 number of events per patient-year
Standard Deviation 6.75
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
Severe nocturnal symptomatic hypoglycemia: any severe symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=1 Episodes
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.
|
NPH Insulin
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.
|
|---|---|---|
|
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
|
0.04 number of events per patient-year
Standard Deviation 0.29
|
0.00 number of events per patient-year
Standard Deviation 0.00
|
SECONDARY outcome
Timeframe: baseline, 6 monthsPopulation: 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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment
Baseline HbA1c
|
8.023 percent HbA1c
Standard Deviation 1.049
|
8.248 percent HbA1c
Standard Deviation 1.429
|
|
Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment
Absolute change from baseline (N = 59 & 57)
|
0.036 percent HbA1c
Standard Deviation 0.979
|
0.000 percent HbA1c
Standard Deviation 1.035
|
|
Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment
End of treatment HbA1c (N = 59 & 57)
|
8.071 percent HbA1c
Standard Deviation 0.884
|
8.344 percent HbA1c
Standard Deviation 1.161
|
SECONDARY outcome
Timeframe: baseline, 6 monthsPopulation: Same as for primary endpoint: mITT population.
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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)
End of treatment HbA1c (ANCOVA)
|
8.139 percent HbA1c
Standard Error 0.1065
|
8.232 percent HbA1c
Standard Error 0.1134
|
|
Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)
Absolute change from baseline HbA1c (ANCOVA)
|
-0.048 percent HbA1c
Standard Error 0.1065
|
0.045 percent HbA1c
Standard Error 0.1134
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=59 Participants
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.
|
NPH Insulin
n=57 Participants
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.
|
|---|---|---|
|
Percentage of Patients Reaching HbA1c Target of Less Than 7.5% at the End of Treatment Visit
|
22.0 percentage of participants
|
22.8 percentage of participants
|
SECONDARY outcome
Timeframe: baseline, 6 monthsPopulation: 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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment
Absolute change from baseline (N= 60 & 62)
|
-0.218 mmol/L
Standard Deviation 2.399
|
0.501 mmol/L
Standard Deviation 1.906
|
|
Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment
Baseline daily BG (N= 61 & 63)
|
11.263 mmol/L
Standard Deviation 1.887
|
11.170 mmol/L
Standard Deviation 1.986
|
|
Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment
End of treatment daily BG (N= 60 & 63)
|
11.085 mmol/L
Standard Deviation 2.077
|
11.712 mmol/L
Standard Deviation 2.166
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
Definitions of the different types of hypoglycemia events provided in the outcome measure description of the corresponding event rates.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with "All hypoglycemia"
|
61 participants
|
63 participants
|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with symptomatic hypoglycemia
|
40 participants
|
44 participants
|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with severe symptomatic hypoglycemia
|
4 participants
|
2 participants
|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with nocturnal hypoglycemia
|
59 participants
|
60 participants
|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with nocturnal symptomatic hypoglycemia
|
17 participants
|
28 participants
|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with severe noct. sympto. hypoglycemia
|
1 participants
|
0 participants
|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with "All confirmed low CGMS excursions"
|
60 participants
|
61 participants
|
|
Number of Patients With Different Types of Hypoglycemia Events
Patients with "All confirmed low FSBG"
|
61 participants
|
63 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsPopulation: 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).
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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=60 Participants
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.
|
NPH Insulin
n=63 Participants
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.
|
|---|---|---|
|
Percent of Blood Glucose (BG) Within the Range of 70 - 180 mg/dL (3.9-10 mmol/L)
|
41.667 percent of CGMS values within the range
Standard Deviation 12.048
|
38.158 percent of CGMS values within the range
Standard Deviation 10.908
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsPopulation: 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).
Calculated for any given patient as the standard deviation (SD) of all CGMS interstitial glucose values recorded over all CGMS placements.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=60 Participants
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.
|
NPH Insulin
n=63 Participants
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.
|
|---|---|---|
|
Blood Glucose Variability Based on All On-treatment CGMS Values
|
4.954 mmol/L
Standard Deviation 0.826
|
5.089 mmol/L
Standard Deviation 0.731
|
POST_HOC outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
"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.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
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)
|
74.61 events per patient-year
Standard Deviation 74.09
|
71.60 events per patient-year
Standard Deviation 53.20
|
POST_HOC outcome
Timeframe: 6 monthsPopulation: Same as for primary endpoint: mITT population.
"All confirmed low FSBG" consisted of all low FSBG readings (values \<70 mg/dL) performed at other times.
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=61 Participants
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.
|
NPH Insulin
n=64 Participants
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.
|
|---|---|---|
|
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)
|
192.69 events per patient-year
Standard Deviation 121.78
|
168.24 events per patient-year
Standard Deviation 101.21
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsPopulation: 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).
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).
Outcome measures
| Measure |
Lantus (Insulin Glargine)
n=60 Participants
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.
|
NPH Insulin
n=63 Participants
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.
|
|---|---|---|
|
Nocturnal Blood Glucose Variability Based on All On-treatment CGMS Values
|
4.747 mmol/L
Standard Deviation 0.973
|
4.837 mmol/L
Standard Deviation 0.825
|
Adverse Events
Lantus
Serious events: 8 serious events
Other events: 30 other events
Deaths: 0 deaths
NPH Insulin
Serious events: 2 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lantus
n=62 participants at risk
|
NPH Insulin
n=63 participants at risk
|
|---|---|---|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
1.6%
1/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
1.6%
1/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Gastrointestinal disorders
Gastritis
|
3.2%
2/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
0.00%
0/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.6%
1/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
0.00%
0/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Viral infection
|
1.6%
1/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
0.00%
0/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
1.6%
1/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Metabolism and nutrition disorders
Hypoglycaemic seizure
|
3.2%
2/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
0.00%
0/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.6%
1/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
0.00%
0/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
Other adverse events
| Measure |
Lantus
n=62 participants at risk
|
NPH Insulin
n=63 participants at risk
|
|---|---|---|
|
Infections and infestations
Gastroenteritis
|
9.7%
6/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
9.5%
6/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Nasopharyngitis
|
9.7%
6/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
7.9%
5/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Pharyngitis
|
9.7%
6/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
3.2%
2/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.5%
4/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
9.5%
6/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Bronchitis
|
4.8%
3/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
7.9%
5/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Otitis media
|
1.6%
1/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
6.3%
4/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Infections and infestations
Tonsillitis
|
1.6%
1/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
6.3%
4/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.2%
2/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
6.3%
4/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
Gastrointestinal disorders
Vomiting
|
8.1%
5/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
6.3%
4/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
General disorders
Device lead damage
|
8.1%
5/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
3.2%
2/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
|
General disorders
Pyrexia
|
4.8%
3/62 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
11.1%
7/63 • Adverse events were monitored from baseline to 7 days after last treatment visit.
The safety analyses were conducted according to the treatment received rather than according to the randomization groups.
|
Additional Information
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 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.
- Publication restrictions are in place
Restriction type: OTHER