Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Children and Adolescents With Type 1 Diabetes Mellitus
- Conditions
- Type 1 Diabetes Mellitus
- Interventions
- Drug: Insulin glargine (100 units /mL)Drug: Insulin glargine,300 U/mLDrug: Background therapy
- Registration Number
- NCT02735044
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To compare the efficacy of a new formulation of insulin glargine (HOE901-U300) to Lantus in terms of change of HbA1c from baseline to endpoint (month 6) in children and adolescents with type 1 diabetes mellitus.
.
Secondary Objectives:
To compare HOE901-U300 and Lantus in terms of:
* Percentage of participants reaching target HbA1c and fasting plasma glucose (FPG).
* To assess the safety of HOE901-U300 including analysis of events of hypoglycemia, events of hyperglycemia with ketosis, and development of anti-insulin-antibodies.
- Detailed Description
The study duration per participant was approximately 58 weeks that consisted of a 2 week screening period, a main 6-month comparative efficacy and safety treatment period, a 6-month comparative safety extension period, and a 4-week post treatment follow up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 463
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lantus Insulin glargine (100 units /mL) Lantus (Insulin glargine 100 U/mL) SC injection once daily for 12 months. HOE901-U300 Background therapy HOE901-U300 (Insulin glargine 300 Units/milliliter \[U/mL\]) Subcutaneous(SC) injection once daily for 12 months. HOE901-U300 Insulin glargine,300 U/mL HOE901-U300 (Insulin glargine 300 Units/milliliter \[U/mL\]) Subcutaneous(SC) injection once daily for 12 months. Lantus Background therapy Lantus (Insulin glargine 100 U/mL) SC injection once daily for 12 months.
- Primary Outcome Measures
Name Time Method Change From Baseline in HbA1c to Month 6 Baseline to Month 6 Change in HbA1c was calculated by subtracting baseline value from Month 6 value. Adjusted least-square (LS) means and standard errors (SE) were obtained using analysis of covariance (ANCOVA) after multiple imputations of missing data using post-baseline HbA1c data available on the main 6-month randomized period.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) Without Any Episode of Severe and/or Documented (SMPG <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period upto Month 6 Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Percentage of Participants With HbA1c Values of <7.5% at Month 6 Month 6 Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6 Baseline to Month 6 Change in FPG was calculated by subtracting baseline value from Month 6 value. Adjusted LS means and SE were obtained using ANCOVA after multiple imputation to address missing data in the main 6 month randomized period.
Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6 Month 6 Participants without any available FPG assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6 Baseline to Month 6 8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (\<8.5%; \>=8.5%), randomization strata of age at screening (\<12 years, \>=12 years) and the baseline 24-hour average 8-point profile SMPG.
Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6 Baseline, Month 6 8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Variability was assessed by the coefficient of variation (standard deviation divided by mean) calculated over the 8-point SMPG. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point Baseline to Month 6 8-point SMPG profiles were measured for following 8 time points at Baseline and Month 6: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.
Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 Month 12 Severe hypoglycemia: an event in which the child/adolescent having altered mental status and cannot assist in their care, is semiconscious or unconscious, or in coma ± convulsions and may require parenteral therapy (glucagon or glucose). Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=70 mg/dL (3.9 mmol/L). Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration \<=70 mg/dL. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia were not accompanied by plasma glucose determination but was presumably caused by a plasma glucose concentration \<=70 mg/dL. Pseudo-hypoglycemia:an event with any of the typical symptoms of hypoglycaemia with plasma glucose concentration \>70 mg/dL.
Percentage of Participants With HbA1c Values of <7.5% Without Any Episode of Severe and/or Documented Self-Monitored Plasma Glucose ([SMPG] <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period upto Month 6 Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12 Month 12 Hyperglycemia with ketosis was defined as SMPG \>=252 mg/dL (14 mmol/L) with accompanying self-measured blood ketones \>=1.5 mmol/L.
Trial Locations
- Locations (107)
Investigational Site Number 1000005
🇧🇬Sofia, Bulgaria
Investigational Site Number 1520004
🇨🇱Santiago, Chile
Investigational Site Number 2030005
🇨🇿Ostrava - Poruba, Czechia
Investigational Site Number 0760001
🇧🇷Sao Paulo, Brazil
Investigational Site Number 1240003
🇨🇦Halifax, Canada
Investigational Site Number 2030003
🇨🇿Hradec Kralove, Czechia
Investigational Site Number 2080001
🇩🇰Herlev, Denmark
Investigational Site Number 8260001
🇬🇧Ipswich, United Kingdom
Investigational Site Number 2030001
🇨🇿Praha 5 - Motol, Czechia
Investigational Site Number 1240006
🇨🇦Sherbrooke, Canada
Investigational Site Number 1520002
🇨🇱Santiago, Chile
Investigational Site Number 8260004
🇬🇧Kettering, United Kingdom
Investigational Site Number 7240005
🇪🇸Barcelona, Spain
Investigational Site Number 7240001
🇪🇸Vitoria, Spain
Investigational Site Number 2500003
🇫🇷Montpellier, France
Investigational Site Number 8260005
🇬🇧Doncaster, United Kingdom
Investigational Site Number 8260002
🇬🇧Salisbury, United Kingdom
Investigational Site Number 7520002
🇸🇪Stockholm, Sweden
Investigational Site Number 7240002
🇪🇸Barcelona, Spain
Investigational Site Number 6880002
🇷🇸Belgrade, Serbia
Investigational Site Number 7240004
🇪🇸Sabadell, Spain
Investigational Site Number 7240003
🇪🇸Esplugues De Llobregat, Spain
Investigational Site Number 7240006
🇪🇸Santa Cruz De Tenerife, Spain
Investigational Site Number 8400032
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 8400037
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 8400015
🇺🇸Buffalo, New York, United States
Investigational Site Number 8400016
🇺🇸Chapel Hill, North Carolina, United States
Investigational Site Number 8400035
🇺🇸Morehead City, North Carolina, United States
Investigational Site Number 8400038
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 8400030
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number 8400029
🇺🇸Lufkin, Texas, United States
Investigational Site Number 8400034
🇺🇸Seattle, Washington, United States
Investigational Site Number 0320003
🇦🇷Caba, Argentina
Investigational Site Number 0320001
🇦🇷Caba, Argentina
Investigational Site Number 0320002
🇦🇷Capital Federal, Argentina
Investigational Site Number 0320006
🇦🇷Mendoza, Argentina
Investigational Site Number 0320005
🇦🇷Salta, Argentina
Investigational Site Number 8400008
🇺🇸Tucson, Arizona, United States
Investigational Site Number 0760005
🇧🇷Curitiba, Brazil
Investigational Site Number 0760006
🇧🇷Fortaleza, Brazil
Investigational Site Number 1520003
🇨🇱Viña Del Mar, Chile
Investigational Site Number 2760004
🇩🇪Leipzig, Germany
Investigational Site Number 3800003
🇮🇹Verona, Italy
Investigational Site Number 3920006
🇯🇵Chiyoda-Ku, Japan
Investigational Site Number 3920003
🇯🇵Hiroshima-Shi, Japan
Investigational Site Number 4840001
🇲🇽Monterrey, Mexico
Investigational Site Number 1000004
🇧🇬Varna, Bulgaria
Investigational Site Number 0320004
🇦🇷Capital Federal, Argentina
Investigational Site Number 1000001
🇧🇬Plovdiv, Bulgaria
Investigational Site Number 1520006
🇨🇱Santiago, Chile
Investigational Site Number 2760002
🇩🇪Hannover, Germany
Investigational Site Number 8400010
🇺🇸Rapid City, South Dakota, United States
Investigational Site Number 0320007
🇦🇷San Miguel De Tucuman, Argentina
Investigational Site Number 0760004
🇧🇷Fortaleza, Brazil
Investigational Site Number 0760003
🇧🇷Porto Alegre, Brazil
Investigational Site Number 0760002
🇧🇷Sao Paulo, Brazil
Investigational Site Number 1240002
🇨🇦Montreal, Canada
Investigational Site Number 1240005
🇨🇦Montreal, Canada
Investigational Site Number 3480007
🇭🇺Székesfehérvár, Hungary
Investigational Site Number 3760002
🇮🇱Petach Tikva, Israel
Investigational Site Number 2760001
🇩🇪Heidelberg, Germany
Investigational Site Number 3760003
🇮🇱Beer Sheva, Israel
Investigational Site Number 3480004
🇭🇺Budapest, Hungary
Investigational Site Number 3480003
🇭🇺Budapest, Hungary
Investigational Site Number 3800005
🇮🇹Roma, Italy
Investigational Site Number 1520007
🇨🇱Temuco, Chile
Investigational Site Number 3480006
🇭🇺Pécs, Hungary
Investigational Site Number 3800006
🇮🇹Varese, Italy
Investigational Site Number 3920007
🇯🇵Kobe-Shi, Japan
Investigational Site Number 3920005
🇯🇵Osaka-Shi, Japan
Investigational Site Number 3920004
🇯🇵Shinjuku-Ku, Japan
Investigational Site Number 4280002
🇱🇻Daugavpils, Latvia
Investigational Site Number 4280001
🇱🇻Rīga, Latvia
Investigational Site Number 6160003
🇵🇱Warszawa, Poland
Investigational Site Number 6430002
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 6880003
🇷🇸Belgrade, Serbia
Investigational Site Number 2500002
🇫🇷Toulouse, France
Investigational Site Number 3480001
🇭🇺Budapest, Hungary
Investigational Site Number 2760003
🇩🇪Münster, Germany
Investigational Site Number 3480005
🇭🇺Gyula, Hungary
Investigational Site Number 3480002
🇭🇺Miskolc, Hungary
Investigational Site Number 3760001
🇮🇱Haifa, Israel
Investigational Site Number 3760006
🇮🇱Holon, Israel
Investigational Site Number 3800004
🇮🇹Torino, Italy
Investigational Site Number 3920002
🇯🇵Fukuoka-Shi, Japan
Investigational Site Number 4840002
🇲🇽Puebla, Mexico
Investigational Site Number 6160001
🇵🇱Gdansk, Poland
Investigational Site Number 3800001
🇮🇹Firenze, Italy
Investigational Site Number 4840004
🇲🇽México, Mexico
Investigational Site Number 6160004
🇵🇱Warszawa, Poland
Investigational Site Number 6420005
🇷🇴Bucharest, Romania
Investigational Site Number 4840003
🇲🇽Durango, Mexico
Investigational Site Number 8070001
🇲🇰Skopje, North Macedonia
Investigational Site Number 6160005
🇵🇱Bielsko-Biala, Poland
Investigational Site Number 6160006
🇵🇱Szczecin, Poland
Investigational Site Number 6420006
🇷🇴Sibiu, Romania
Investigational Site Number 6430004
🇷🇺Smolensk, Russian Federation
Investigational Site Number 4840005
🇲🇽Veracruz, Mexico
Investigational Site Number 6420007
🇷🇴Constanta, Romania
Investigational Site Number 6420003
🇷🇴Timisoara, Romania
Investigational Site Number 6430003
🇷🇺Ufa, Russian Federation
Investigational Site Number 6880004
🇷🇸Nis, Serbia
Investigational Site Number 6430001
🇷🇺Moscow, Russian Federation
Investigational Site Number 6160007
🇵🇱Warszawa, Poland
Investigational Site Number 6420004
🇷🇴Craiova, Romania
Investigational Site Number 8400005
🇺🇸Dallas, Texas, United States
Investigational Site Number 8400021
🇺🇸Dallas, Texas, United States