Trial Outcomes & Findings for Comparison of SAR341402 to NovoLog in Adult Patients With Type 1 Diabetes Mellitus Also Using Insulin Glargine (NCT NCT03874715)

NCT ID: NCT03874715

Last Updated: 2024-04-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 210 participants
• Primary outcome timeframe: 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
• Results posted on: 2024-04-17

Participant Flow

Study was conducted at 31 active sites in the United States. A total of 279 participants were screened from 11 March 2019 to 30 Oct 2019, out of which 210 participants were randomized. Participants were randomized in 1:1 ratio to "switching arm" (NovoLog/SAR341402) and "non-switching arm" (NovoLog). Randomization was stratified by glycated hemoglobin A1c (HbA1c) (less than [<] 8.0 percent [%] and greater than or equal to [>=] 8.0%) obtained at screening visit.

Participants not treated with NovoLog and insulin glargine (100 units per milliliter [U/mL] for at least 12 weeks prior to screening, completed a mandatory run-in period of up to 12-weeks and were administered NovoLog and Lantus. Run-in period duration was considered as a sufficient duration to ensure that, at the time of randomization, all the participants had received NovoLog and insulin glargine (100 U/mL) for at least 12 weeks.

Participant milestones

Measure	Switching: NovoLog/SAR341402 Participants self-administered subcutaneous (SC) injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Overall Study STARTED	104	106
Overall Study Treated	104	106
Overall Study Safety Population	99	111
Overall Study Anti-insulin Antibody (AIA) Population	98	107
Overall Study COMPLETED	95	105
Overall Study NOT COMPLETED	9	1

Reasons for withdrawal

Measure	Switching: NovoLog/SAR341402 Participants self-administered subcutaneous (SC) injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Overall Study Adverse Event	2	0
Overall Study Poor compliance to protocol	5	1
Overall Study Withdrawal by Subject	1	0
Overall Study Other-unspecified	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Switching: NovoLog/SAR341402 n=104 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=106 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Total n=210 Participants Total of all reporting groups
Age, Continuous	43.8 years STANDARD_DEVIATION 16.2 • n=5 Participants	44.3 years STANDARD_DEVIATION 15.8 • n=7 Participants	44.1 years STANDARD_DEVIATION 16.0 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	40 Participants n=7 Participants	84 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	66 Participants n=7 Participants	126 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) White	91 Participants n=5 Participants	90 Participants n=7 Participants	181 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=58 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=71 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Measurable Timepoint (AUClast) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)	8960 picograms*hour per milliliter (pg*h/mL) Standard Deviation 18300	7190 picograms*hour per milliliter (pg*h/mL) Standard Deviation 6530

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=55 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=66 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)	6720 pg*h/mL Standard Deviation 3700	7260 pg*h/mL Standard Deviation 6370

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=58 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=71 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)	11800 picograms per milliliter (pg/mL) Standard Deviation 65600	3330 picograms per milliliter (pg/mL) Standard Deviation 8850

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=98 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=107 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Number of Participants With Treatment-emergent Anti-Insulin Aspart Antibodies (AIAs) Treatment-emergent AIA	8 Participants	11 Participants
Number of Participants With Treatment-emergent Anti-Insulin Aspart Antibodies (AIAs) Treatment-boosted AIA	0 Participants	1 Participants
Number of Participants With Treatment-emergent Anti-Insulin Aspart Antibodies (AIAs) Treatment-induced AIA	8 Participants	10 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=99 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=111 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Number of Participants With at Least One Hypoglycemic Event Any hypoglycemia	95 Participants	105 Participants
Number of Participants With at Least One Hypoglycemic Event Severe hypoglycemia	6 Participants	4 Participants
Number of Participants With at Least One Hypoglycemic Event Documented symptomatic hypoglycemia <=3.9 mmol/L	89 Participants	98 Participants
Number of Participants With at Least One Hypoglycemic Event Documented symptomatic hypoglycemia < 3.0 mmol/L	78 Participants	90 Participants
Number of Participants With at Least One Hypoglycemic Event Asymptomatic hypoglycemia <= 3.9 mmol/L	69 Participants	68 Participants
Number of Participants With at Least One Hypoglycemic Event Asymptomatic hypoglycemia < 3.0 mmol/L	48 Participants	44 Participants
Number of Participants With at Least One Hypoglycemic Event Probable symptomatic hypoglycemia	8 Participants	9 Participants
Number of Participants With at Least One Hypoglycemic Event Relative hypoglycemia	3 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=99 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=111 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Number of Hypoglycemic Events Per Participant-year Any hypoglycemia	103.18 events per participant-year	97.09 events per participant-year
Number of Hypoglycemic Events Per Participant-year Severe hypoglycemia	0.76 events per participant-year	0.38 events per participant-year
Number of Hypoglycemic Events Per Participant-year Documented symptomatic hypoglycemia <= 3.9 mmol/L	64.29 events per participant-year	63.54 events per participant-year
Number of Hypoglycemic Events Per Participant-year Documented symptomatic hypoglycemia < 3.0 mmol/L	27.72 events per participant-year	25.70 events per participant-year
Number of Hypoglycemic Events Per Participant-year Asymptomatic hypoglycemia <= 3.9 mmol/L	37.33 events per participant-year	32.25 events per participant-year
Number of Hypoglycemic Events Per Participant-year Asymptomatic hypoglycemia < 3.0 mmol/L	9.11 events per participant-year	7.03 events per participant-year
Number of Hypoglycemic Events Per Participant-year Probable symptomatic hypoglycemia	0.70 events per participant-year	0.81 events per participant-year
Number of Hypoglycemic Events Per Participant-year Relative hypoglycemia	0.09 events per participant-year	0.12 events per participant-year

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=99 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=111 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TEAEs	25 Participants	47 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TESAEs	5 Participants	5 Participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Switching: NovoLog/SAR341402 n=58 Participants Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=71 Participants Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)	1.33 hours Interval 0.3 to 3.25	1.00 hours Interval 0.37 to 3.13

Adverse Events

Switching: NovoLog/SAR341402

Serious events: 5 serious events

Other events: 3 other events

Deaths: 0 deaths

Non-switching: NovoLog

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Switching: NovoLog/SAR341402 n=99 participants at risk Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=111 participants at risk Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Infections and infestations Gastroenteritis Viral	0.00% 0/99 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	0.90% 1/111 • Number of events 1 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.
Metabolism and nutrition disorders Hypoglycaemia	2.0% 2/99 • Number of events 2 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	0.90% 1/111 • Number of events 1 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.
Psychiatric disorders Alcohol Abuse	0.00% 0/99 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	1.8% 2/111 • Number of events 2 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.
Nervous system disorders Seizure	1.0% 1/99 • Number of events 1 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	0.00% 0/111 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/99 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	0.90% 1/111 • Number of events 1 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.
Gastrointestinal disorders Colitis	1.0% 1/99 • Number of events 1 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	0.00% 0/111 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.
Injury, poisoning and procedural complications Accidental Overdose	1.0% 1/99 • Number of events 1 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	0.00% 0/111 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.

Other adverse events

Measure	Switching: NovoLog/SAR341402 n=99 participants at risk Participants self-administered SC injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 U/mL) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.	Non-switching: NovoLog n=111 participants at risk Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.
Infections and infestations Nasopharyngitis	2.0% 2/99 • Number of events 2 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	5.4% 6/111 • Number of events 6 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.
Infections and infestations Upper Respiratory Tract Infection	1.0% 1/99 • Number of events 1 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.	5.4% 6/111 • Number of events 6 • From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113) 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.

Additional Information

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