Comparison of SAR341402 to NovoLog/NovoRapid in Adult Patients With Diabetes Mellitus Also Using Insulin Glargine
- Conditions
- Type 1 Diabetes Mellitus-Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT03211858
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To demonstrate non-inferiority of SAR341402 versus NovoLog/NovoRapid in glycated hemoglobin A1c (HbA1c) change from baseline to Week 26 in participants with type 1 or type 2 diabetes mellitus (T1DM or T2DM) also using Lantus®.
Secondary Objectives:
* To assess the immunogenicity of SAR341402 and NovoLog/NovoRapid in terms of positive/negative status and anti-insulin antibody (AIA) titers during the course of the study.
* To assess the relationship of AIAs with efficacy and safety.
* To assess the efficacy of SAR341402 and NovoLog/NovoRapid in terms of proportion of participants reaching HbA1c lesser than (\<) 7.0% and change in HbA1c, fasting plasma glucose (FPG), and self-measured plasma glucose (SMPG) profiles from baseline to Week 26 and Week 52 (only Week 52 for HbA1c).
* To assess safety of SAR341402 and NovoLog/NovoRapid.
- Detailed Description
The study consisted of a 2-week screening period, a 26-week treatment period, a 26-week comparative safety extension period, and a 1-day follow-up period. The maximum study duration was 54 weeks per participant and a 1 day safety follow-up.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 597
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR341402 Insulin glargine (HOE901) SAR341402 subcutaneous (SC), before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52. NovoLog/NovoRapid NovoLog/NovoRapid NovoLog/NovoRapid SC, before meals intake on top of QD Insulin Glargine, up to Week 52. NovoLog/NovoRapid Insulin glargine (HOE901) NovoLog/NovoRapid SC, before meals intake on top of QD Insulin Glargine, up to Week 52. SAR341402 Insulin aspart SAR341402 subcutaneous (SC), before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.
- Primary Outcome Measures
Name Time Method Change in Glycated Hemoglobin A1c (HbA1c) From Baseline to Week 26 Baseline, Week 26 All values up to Week 26 were taken into account in the analysis, regardless of adherence to treatment. Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Missing changes at Week 26 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted least square (LS) means and standard errors (SE) were obtained using an analysis of covariance (ANCOVA) model on data obtained from the multiple imputations (results were combined using Rubin's formulae).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions From first injection of IMP up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52 Participants with at least one treatment-emergent adverse event linked to hypersensitivity reaction and injection site reaction regardless of relationship to IMP during the main 6-month and the 12-month on-treatment periods was assessed and reported.
Percentage of Participants With at Least One Positive Anti-Insulin Aspart Antibodies (AIA) Sample From first injection of IMP up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52 Participants with at least one positive AIA sample at baseline or at any time during the on-treatment period (Prevalence).
Change in HbA1c From Baseline to Week 52 Baseline, Week 52 All values up to Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in HbA1c was calculated by subtracting baseline value from Week 52 value. Missing changes at Week 52 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted LS means and SE were obtained using ANCOVA model on data obtained from the multiple imputations (results were combined using Rubin's formulae).
Percentage of Participants With HbA1c <7% at Week 26 and Week 52 Week 26 and Week 52 Participants who had no available assessment at Week 26 and Week 52 were considered as non-responders.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 and Week 52 Baseline, Week 26, and Week 52 All values up to Week 26 and Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in FPG at Week 26 and 52 was calculated by subtracting baseline value from Week 26 and Week 52 values, respectively. Missing changes at Week 26 and Week 52 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).
Change in the Mean 24-hour Plasma Glucose Concentration From Baseline to Week 26 and Week 52 Baseline, Week 26, and Week 52 Mean 24-hour plasma glucose concentration was calculated based on 7-point self-measured plasma glucose (SMPG) profiles with plasma glucose measurements before and 2-hours after each main meal and at bedtime. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in the week before a visit. All calculated values up to Week 26 and Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in mean 24-hour plasma glucose concentration at Weeks 26 and 52 was calculated by subtracting baseline value from Week 26 and Week 52 values, respectively. Missing changes at Week 26 and Week 52 were imputed using a return-to-baseline multiple imputation method (values imputed as participant baseline plus an error). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).
Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52 Baseline, Week 26, and Week 52 Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour PPG minus plasma glucose value obtained 30 minutes prior to start of the meal. Values of plasma glucose excursions at each visit were then calculated as the average across profiles performed in the week before the visit. All calculated values up to Week 26 and Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in PPG excursions at Weeks 26 and 52 was calculated by subtracting baseline value from Week 26 and Week 52 values, respectively. Missing changes at Week 26 and Week 52 were imputed using a return-to-baseline multiple imputation method (values imputed as participant baseline plus an error). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Baseline, Week 26, and Week 52 7-point SMPG profiles were measured at the following 7 points at each visit (Baseline, Week 26, and Week 52): before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, and bedtime. For each time point, the value at each visit was calculated as the average of values obtained for the same time point across profiles performed in the week before the visit.
Number of Participants With at Least One Hypoglycemic Event From first injection of investigational medicinal product (IMP) up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52 Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (\<=70 mg/dL) or plasma glucose level of \<3.0 mmol/L (\<54 mg/dL).
Number of Hypoglycemia Events Per Participant-Year From first injection of investigational medicinal product (IMP) up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52 Number of hypoglycemia events (any, severe and documented \[both thresholds\]) per participant-year of exposure were reported. Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (\<=70 mg/dL) or plasma glucose level of \<3.0 mmol/L (\<54 mg/dL).
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) From first injection of IMP up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52 AIA incidence were categorized as: treatment-induced, treatment-boosted AIAs, and treatment-emergent AIA. 1) Participants with treatment-induced AIAs were those who developed AIA following IMP administration (participants with at least one positive AIA sample at any time during on-treatment period, in those participants without pre-existing AIA or with missing baseline sample). 2) Participants with treatment-boosted AIAs were those with pre-existing AIAs that were boosted to a significant higher titer following IMP administration (participants with at least one AIA sample with at least a 4-fold increase in titers compared to baseline value at any time during on-treatment period). 3) Participants with treatment-emergent AIA were defined as participants with treatment-induced, or treatment-boosted AIAs.
Trial Locations
- Locations (82)
Investigational Site Number 8400033
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 8400009
🇺🇸Dallas, Texas, United States
Investigational Site Number 8400024
🇺🇸Henderson, Nevada, United States
Investigational Site Number 8400037
🇺🇸Aurora, Colorado, United States
Investigational Site Number 8400022
🇺🇸Columbus, Georgia, United States
Investigational Site Number 8400044
🇺🇸Austin, Texas, United States
Investigational Site Number 8400005
🇺🇸Des Moines, Iowa, United States
Investigational Site Number 8400018
🇺🇸Englewood, Colorado, United States
Investigational Site Number 8400032
🇺🇸Roswell, Georgia, United States
Investigational Site Number 3480011
🇭🇺Budapest, Hungary
Investigational Site Number 3480001
🇭🇺Budapest, Hungary
Investigational Site Number 3920005
🇯🇵Kumamoto-Shi, Japan
Investigational Site Number 3920010
🇯🇵Osaka-Shi, Japan
Investigational Site Number 3920009
🇯🇵Fukuyama-Shi, Japan
Investigational Site Number 2460006
🇫🇮Jyväskylä, Finland
Investigational Site Number 2460002
🇫🇮Kuopio, Finland
Investigational Site Number 2460004
🇫🇮Pori, Finland
Investigational Site Number 8400013
🇺🇸Ventura, California, United States
Investigational Site Number 3920008
🇯🇵Higashiosaka-Shi, Japan
Investigational Site Number 3920001
🇯🇵Koriyama-Shi, Japan
Investigational Site Number 2760006
🇩🇪Essen, Germany
Investigational Site Number 8400008
🇺🇸Renton, Washington, United States
Investigational Site Number 2760001
🇩🇪Berlin, Germany
Investigational Site Number 3920003
🇯🇵Mito-Shi, Japan
Investigational Site Number 3920002
🇯🇵Sagamihara-Shi, Japan
Investigational Site Number 3920004
🇯🇵Shinjuku-Ku, Japan
Investigational Site Number 8400039
🇺🇸Bridgeport, West Virginia, United States
Investigational Site Number 2760004
🇩🇪Heidelberg, Germany
Investigational Site Number 3920006
🇯🇵Ushiku-Shi, Japan
Investigational Site Number 8400017
🇺🇸Houston, Texas, United States
Investigational Site Number 8400001
🇺🇸Houston, Texas, United States
Investigational Site Number 8400020
🇺🇸Houston, Texas, United States
Investigational Site Number 8400034
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 3480009
🇭🇺Szentendre, Hungary
Investigational Site Number 3480012
🇭🇺Balatonfüred, Hungary
Investigational Site Number 3480007
🇭🇺Debrecen, Hungary
Investigational Site Number 6160001
🇵🇱Poznan, Poland
Investigational Site Number 3480005
🇭🇺Budapest, Hungary
Investigational Site Number 3480010
🇭🇺Nyíregyháza, Hungary
Investigational Site Number 3480008
🇭🇺Budapest, Hungary
Investigational Site Number 6160003
🇵🇱Krakow, Poland
Investigational Site Number 3480004
🇭🇺Budapest, Hungary
Investigational Site Number 3480003
🇭🇺Nagykanizsa, Hungary
Investigational Site Number 6160004
🇵🇱Bialystok, Poland
Investigational Site Number 6160005
🇵🇱Krakow, Poland
Investigational Site Number 6430002
🇷🇺Samara, Russian Federation
Investigational Site Number 6430003
🇷🇺Saratov, Russian Federation
Investigational Site Number 8400002
🇺🇸Escondido, California, United States
Investigational Site Number 8400011
🇺🇸Santa Barbara, California, United States
Investigational Site Number 8400014
🇺🇸La Jolla, California, United States
Investigational Site Number 8400012
🇺🇸Concord, California, United States
Investigational Site Number 8400030
🇺🇸Fresno, California, United States
Investigational Site Number 8400040
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 8400036
🇺🇸Pomona, California, United States
Investigational Site Number 8400004
🇺🇸Greenbrae, California, United States
Investigational Site Number 8400027
🇺🇸Ocoee, Florida, United States
Investigational Site Number 8400007
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 8400038
🇺🇸Arlington Heights, Illinois, United States
Investigational Site Number 8400041
🇺🇸Metairie, Louisiana, United States
Investigational Site Number 8400028
🇺🇸New York, New York, United States
Investigational Site Number 8400003
🇺🇸Omaha, Nebraska, United States
Investigational Site Number 8400025
🇺🇸Morehead City, North Carolina, United States
Investigational Site Number 8400029
🇺🇸Bend, Oregon, United States
Investigational Site Number 8400035
🇺🇸Dallas, Texas, United States
Investigational Site Number 8400021
🇺🇸Dallas, Texas, United States
Investigational Site Number 8400016
🇺🇸Mesquite, Texas, United States
Investigational Site Number 2460003
🇫🇮Seinäjoki, Finland
Investigational Site Number 2760002
🇩🇪Pirna, Germany
Investigational Site Number 6160007
🇵🇱Lublin, Poland
Investigational Site Number 6160006
🇵🇱Nowy Sacz, Poland
Investigational Site Number 6160002
🇵🇱Warszawa, Poland
Investigational Site Number 6430001
🇷🇺St. Petersburg, Russian Federation
Investigational Site Number 6430004
🇷🇺Tomsk, Russian Federation
Investigational Site Number 8400042
🇺🇸Waltham, Massachusetts, United States
Investigational Site Number 2760005
🇩🇪Oldenburg In Holstein, Germany
Investigational Site Number 8400043
🇺🇸Los Angeles, California, United States
Investigational Site Number 8400019
🇺🇸Flint, Michigan, United States
Investigational Site Number 8400010
🇺🇸Wilmington, North Carolina, United States
Investigational Site Number 3920007
🇯🇵Kashiwara-Shi, Japan
Investigational Site Number 8400023
🇺🇸Fargo, North Dakota, United States
Investigational Site Number 8400031
🇺🇸New Port Richey, Florida, United States
Investigational Site Number 8400015
🇺🇸Rockville, Maryland, United States