Clinical Trial Results:
A 24-Week, Randomized, Open-Label, Parallel Group, Multicenter Comparison of Lantus® (Insulin Glargine) Given Once Daily Versus Neutral Protamine Hagedorn (NPH) Insulin in Children With Type 1 Diabetes Mellitus Aged At Least 6 Years to Less Than 18 Years
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Summary
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EudraCT number |
2014-004640-35 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
05 Mar 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Apr 2016
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First version publication date |
03 Jun 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EFC11681
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01223131 | ||
WHO universal trial number (UTN) |
U1111-1116-3661 | ||
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Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
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Public contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Apr 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Mar 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the efficacy of insulin glargine given once daily (QD) on glycosylated hemoglobin (HbA1c) levels over a period of 24 weeks in children with type 1 diabetes mellitus (T1DM) aged at least 6 years to less than 18 years.
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Feb 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
China: 162
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Worldwide total number of subjects |
162
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
65
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Adolescents (12-17 years) |
97
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 10 sites in China. A total of 196 subjects were screened between 11 February 2011 and 30 August 2013. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Of 196 screened subjects, 31 were screen failures, 3 subjects were run-in failures and 162 subjects were randomized. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Insulin Glargine | |||||||||||||||||||||
Arm description |
Insulin glargine for 24 weeks (+/- Rapid acting insulin) | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Insulin glargine
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Investigational medicinal product code |
HOE901
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Other name |
Lantus®
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Insulin glargine 100 U/mL once daily at bedtime.
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Arm title
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NPH Insulin | |||||||||||||||||||||
Arm description |
Neutral Protamine Hagedorn Insulin for 24 weeks ( +/- Rapid acting insulin) | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
NPH insulin
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Investigational medicinal product code |
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Other name |
Novolin® N
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
NPH insulin 100 U/mL once daily (at bedtime) or twice daily (in the morning and at bedtime).
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Baseline characteristics reporting groups
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Reporting group title |
Insulin Glargine
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Reporting group description |
Insulin glargine for 24 weeks (+/- Rapid acting insulin) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NPH Insulin
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Reporting group description |
Neutral Protamine Hagedorn Insulin for 24 weeks ( +/- Rapid acting insulin) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Insulin Glargine
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Reporting group description |
Insulin glargine for 24 weeks (+/- Rapid acting insulin) | ||
Reporting group title |
NPH Insulin
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Reporting group description |
Neutral Protamine Hagedorn Insulin for 24 weeks ( +/- Rapid acting insulin) | ||
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End point title |
Absolute Change From Baseline in HbA1c at Week 24 [1] | ||||||||||||
End point description |
Analysis was carried out on modified intent-to-treat (mITT) population defined as all randomized and treated subjects, and had both a baseline assessment and at least one post-baseline assessment. Missing data imputed by Last Observation Carried Forward (LOCF).
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End point type |
Primary
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End point timeframe |
From baseline to week 24
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analysis was performed instead of hypothesis tests due to decrease of sample size during course of the study. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects With HbA1c Value <7.5% at Week 24 | ||||||||||||
End point description |
Analysis was carried out on mITT population.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Fasting Blood Glucose (FBG) at Week 24 | ||||||||||||
End point description |
Analysis was carried out on mITT population. Missing data imputed by LOCF.
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End point type |
Secondary
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End point timeframe |
From baseline to week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Nocturnal Blood Glucose (BG) at Week 24 | ||||||||||||
End point description |
Nocturnal blood glucose was the value measured at 3:00 AM (clock time). Analysis was carried out on mITT population. Missing data imputed by LOCF.
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End point type |
Secondary
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End point timeframe |
From baseline to week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Average Blood Glucose Based on 8-Point Self-Monitoring Blood Glucose (SMBG) | ||||||||||||
End point description |
8-point SMBG was performed at 3:00 hours (clock time), before and 2 hours after each main meal (breakfast, lunch, and dinner), at bedtime (20-22 hours). Analysis was carried out on mITT population. Missing data imputed by LOCF.
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End point type |
Secondary
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End point timeframe |
From baseline to week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Total Insulin Dose And Basal Insulin Dose at Week 24 | ||||||||||||||||||
End point description |
Analysis was carried out on mITT population. Missing data imputed by LOCF
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End point type |
Secondary
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End point timeframe |
From baseline to week 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Subjects With Hypoglycemia | ||||||||||||||||||||||||||||||
End point description |
Asymptomatic hypoglycemia: Blood glucose values <70 mg/dL (3.9 mmol/L) without clinical symptoms and/or signs. Symptomatic hypoglycemia: Any event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying blood glucose <70 mg/dL (3.9 mmol/L). Severe symptomatic hypoglycemia: Any event with clinical symptoms considered to result from a hypoglycemic episode for which the subjects required the assistance of a third party (other than the subject or a parent/usual caregiver), with acute neurological impairment directly resulting from the hypoglycemic event. Nocturnal hypoglycemia: Any asymptomatic and/or symptomatic hypoglycemic event that occured between 23:00 to 07:00 hours. Nocturnal symptomatic hypoglycemia: Any symptomatic hypoglycemic event that occured between 23:00 to 07:00 hours. Analysis was carried out on safety population defined as all randomized and treated subjects and analyzed according to the treatment actually received.
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End point type |
Secondary
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End point timeframe |
During 24-week treatment period
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects With Positive Anti-Insulin Glargine (AGA) Anti-Human Insulin (AIA) Antibody | ||||||||||||||||||||||||||||||
End point description |
Analysis was carried out on antibody population defined as all randomized subjects who contributed at least one evaluable blood sample at screening, or week 4, or week 24 (the end of treatment) for assessment of AGA and AIA.
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End point type |
Secondary
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End point timeframe |
At screening, week 4 and week 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 24) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (defined as the time from the first dose of study drug up to 7 days after the last dose of study drug administration).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Insulin Glargine
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Reporting group description |
Insulin glargine for 24 weeks (+/- Rapid acting insulin). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NPH Insulin
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Reporting group description |
Neutral Protamine Hagedorn Insulin for 24 weeks ( +/- Rapid acting insulin). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Mar 2013 |
- Change to the total sample size: The planned sample size was reduced from 366 to 150 subjects.
- The percentage with insulin glargine PK samples was increased from approximately 30% (about 73 subjects) to approximately 45% (about 45 subjects), in view of reduced sample size for Lantus population.
- In view of smaller sample size, descriptive statistical method was to be used instead of hypothesis tests (ANCOVA for continuous variables and Cochran-Mantel-Haenszel [CMH] for categorical variables) to show inferiority or superiority or estimating model (generalized linear model [GLM] for the event rate of hypoglycemia).
- Based upon the Investigator’s clinical judgment, in cases where screening failure was only due to unqualified HbA1c value (HbA1c at screening <7% or >12%), the subject could be re-screened for this study after 6 months from last screening date. A subject could be randomized in this study only once. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
