Comparison of SAR341402 to NovoLog in Adult Patients With Type 1 Diabetes Mellitus Also Using Insulin Glargine

AUC was defined as area under the concentration versus time curve. Insulin aspart is the active ingredient of SAR341402 and NovoLog.

Time frame: 0 hr (pre-dose), 10, 20, 30, 40 & 50 min, 1 hr, 1 hr-10, 20, 30, 40 & 50 min, 2 hr, 2 hr-15, 30 & 45 min, 3 hr, 3 hr-15, 30 & 45 min, 4 hr, 4 hr-20 & 40 min, 5 hr, 5 hr-20 & 40 min, 6 hr, 6 hr-30 min, 7 hr, 7 hr-30 min & 8 hr post-dose on Day 112

Population: Analysis was performed on PK population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Cmax was defined as the maximum observed plasma concentration. Insulin aspart is the active ingredient of SAR341402 and NovoLog.

Time frame: 0 hr (pre-dose), 10, 20, 30, 40 & 50 min, 1 hr, 1 hr-10, 20, 30, 40 & 50 min, 2 hr, 2hr-15, 30 & 45 min, 3 hr, 3 hr-15, 30 & 45 min, 4 hr, 4 hr-20 & 40 min, 5 hr, 5 hr-20 & 40 min, 6 hr, 6 hr-30 min, 7 hr, 7 hr-30 min & 8 hr post-dose on Day 112

Population: Analysis was performed on PK population.

AUClast was defined as area under the plasma concentration versus time curve from time zero to last measurable timepoint. Insulin aspart was the active ingredient of SAR341402 and NovoLog.

Time frame: 0 hour (hr)(Pre-dose), 10, 20, 30, 40 & 50 minutes (min), 1hr, 1hr-10, 20, 30, 40 & 50min, 2hr, 2hr-15, 30 & 45min, 3hr, 3hr-15, 30 & 45min, 4hr, 4hr-20 & 40min, 5hr, 5hr-20 & 40min, 6hr, 6hr-30min, 7hr, 7hr-30min & 8hr post-dose on Day 112

Population: Analysis was performed on PK population which included all randomized participants without deviation that could significantly impact the PK analysis and for whom PK data were considered sufficient and interpretable.

Number of hypoglycemia events (any, severe, documented \[both threshold\], asymptomatic \[both threshold\], probable symptomatic and relative) per participant-year of exposure were reported. Severe hypoglycemia: event in which participant required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because participant wasn't capable of helping self. Documented symptomatic hypoglycemia: event in which typical SOH were accompanied by measured PGC of \<=3.9 mmol/L (\<70 mg/dL) or \<3.0 mmol/L(\<54 mg/dL). Asymptomatic hypoglycemia: event without SOH and measured PGC of \<=3.9 mmol/L (\<70 mg/dL) or \<3.0 mmol/L(\<54 mg/dL). Probable symptomatic hypoglycemia: event with SOH not accompanied by plasma glucose determination but was presumably caused by PGC \<=3.9 mmol/L (70 mg/dL). Relative hypoglycemia: event with SOH but with measured PGC \>3.9 mmol/L (70 mg/dL).

Time frame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

Population: Analysis was performed on safety population. Five participants randomized to switching arm discontinued IMP during the first treatment of NovoLog before switching to SAR341402, thus included in the non-switching arm for the safety analysis.

Severe hypoglycemia: event in which participant required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because participant was not capable of helping self. Documented symptomatic hypoglycemia: event in which typical symptoms of hypoglycemia (SOH) were accompanied by measured plasma glucose concentration (PGC) less than or equal to (\<=) 3.9 millimoles per liter (mmol/L)(\<70 milligrams per deciliter \[mg/dL\]) or \<3.0 mmol/L(\<54 mg/dL). Asymptomatic hypoglycemia: event without SOH and with measured PGC of \<=3.9 mmol/L (\<70 mg/dL) or \<3.0 mmol/L (\<54 mg/dL). Probable symptomatic hypoglycemia: event with SOH not accompanied by plasma glucose determination but was presumably caused by PGC \<=3.9 mmol/L (70 mg/dL). Relative hypoglycemia: event with SOH but with measured PGC greater than (\>) 3.9 mmol/L (70 mg/dL).

Time frame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

Population: Analysis was performed on safety population which included all randomized participants who received at least one dose of IMP and analyzed according to the treatment actually received. Five participants randomized to switching arm discontinued IMP during the first treatment of NovoLog before switching to SAR341402, thus included in the non-switching arm for the safety analysis.

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) were defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/ incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the on-treatment period (from first injection of IMP up to 1 day after the last injection of IMP).

Time frame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

Population: Analysis was performed on safety population. Five participants randomized to switching arm discontinued IMP during the first treatment of NovoLog before switching to SAR341402, thus included in the non-switching arm for the safety analysis.

AIA was categorized as: treatment-induced AIA, treatment-boosted AIA, and treatment-emergent AIA. Treatment-induced AIAs: participants who developed AIA following investigational medicinal product (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). Treatment-boosted AIAs: participants 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, in those participants with pre-existing AIA). Participants with treatment-emergent AIA were defined as participants with treatment-induced, or treatment-boosted AIAs. On-treatment period was defined as the time from the first injection of IMP up to the last injection of IMP + 1 day.

Time frame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

Population: Analyzed on AIA population which included all randomized participants who received at least one dose of IMP and with at least one AIA sample available for analysis and were analyzed according to treatment actually received. Here, number analyzed = participants with available data for each specified category. Five participants randomized to switching arm discontinued IMP during first treatment of NovoLog before switching to SAR341402, thus included in non-switching arm for the AIA evaluations.

Tmax was defined as the time taken to reach the maximum observed plasma concentration. Insulin aspart is the active ingredient of SAR341402 and NovoLog.

Time frame: 0 hr (pre-dose), 10, 20, 30, 40 & 50 min, 1 hr, 1 hr-10, 20, 30, 40 & 50 min, 2 hr, 2hr-15, 30 & 45 min, 3 hr, 3 hr-15, 30 & 45 min, 4 hr, 4 hr-20 & 40 min, 5 hr, 5 hr-20 & 40 min, 6 hr, 6 hr-30 min, 7 hr, 7 hr-30 min & 8 hr post-dose on Day 112

Population: Analysis was performed on PK population.