SORELLA2: Comparison of SAR342434 to Humalog as the Rapid Acting Insulin in Adult Patients With Type 2 Diabetes Mellitus Also Using Insulin Glargine

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02294474
• Collaborator: (none)
• Enrollment: 505
• Locations: 103
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate non-inferiority of SAR342434 versus Humalog in glycated hemoglobin A1c (HbA1c) change from baseline to Week 26 in participants with type 2 diabetes mellitus (T2DM) also using insulin glargine.

Secondary Objectives:

To assess the immunogenicity of SAR342434 and Humalog in terms of positive/negative status and antibody titers at baseline and during the course of the study; To assess the relationship of anti-insulin antibodies with efficacy and safety. To assess the efficacy of SAR342434 and Humalog on: proportion of participants reaching target HbA1c <7.0% and <=6.5%, fasting plasma glucose (FPG) and self-measured plasma glucose (SMPG) profiles, and insulin dose.

To assess safety of SAR342434 and Humalog.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: SAR342434; Drug: Humalog; Drug: insulin glargine HOE901	Phase 3

Detailed Description

The study will consist of a: up to 2 weeks screening period, 26-week treatment period, and 1-day follow-up period.

The maximum study duration will then be 28 weeks per participant and a 1-day safety follow-up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 505 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Six-month, Randomized, Open-label, Parallel-group Comparison of the Insulin Analog SAR342434 to Humalog® in Adult Patients With Type 2 Diabetes Mellitus Also Using Insulin Glargine
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAR342434 SAR342434 100 Unit/mL (U/mL) before meals intake on top of once daily (QD) Insulin Glargine, up to Week 26.	Drug: SAR342434; SAR342434 100 U/mL (dose range of 1 Unit to 80 Units) self-administered by subcutaneous (SC) injection, immediately (within 5 -10 minutes) before meals intake. Dose adjusted to achieve 2 hour post prandial glucose (PPG) in range of 6.7 to 8.9 mmol/L (120 to 160 mg/dL) while avoiding hypoglycemia.; Drug: insulin glargine HOE901; Insulin glargine 100 U/mL injected QD subcutaneously consistent with the local label. Doses adjusted to achieve glycemic target for fasting, preprandial plasma glucose (SMPG) between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.; Other Names: Lantus®
Active Comparator: Humalog Humalog 100 U/mL before meals intake on top of QD Insulin Glargine, up to Week 26.	Drug: Humalog; Humalog 100 U/ml (dose range of 1 unit to 60 units) self-administered by SC injection, immediately (within 5-10 minutes) before meals intake. Dose adjusted to achieve a 2 hour PPG in range of 6.7 to 8.9 mmol/L (120 to 160 mg/dL) while avoiding hypoglycemia.; Other Names: Insulin Lispro ; Drug: insulin glargine HOE901; Insulin glargine 100 U/mL injected QD subcutaneously consistent with the local label. Doses adjusted to achieve glycemic target for fasting, preprandial plasma glucose (SMPG) between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.; Other Names: Lantus®

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c From Baseline to Week 26 [Baseline, Week 26]

   Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 6-month period and adequate contrasts at Week 26.

Secondary Outcome Measures

1. Percentage of Participants With HbA1c <7.0% and <=6.5% at Week 26 [Week 26]

   Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.

2. Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 [Baseline, Week 26]

   Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM approach to account for missing data, using all post-baseline FPG data available during the 6-month period and adequate contrasts at Week 26.

3. Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to Week 26 [Baseline, Week 26]

   The 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. 7-point SMPGs were performed at least two times in a week before baseline, before visit Week 12 and before visit Week 26. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in the week before a visit. Change in mean 24-hour plasma glucose concentration was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during 6-month period and adequate contrasts at Week 26.

4. Change in Post Prandial Glucose (PPG) Excursion From Baseline to Week 26 [Baseline, Week 26]

   Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour postprandial glucose (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 average across the profiles performed in the week before the visit. Change in PPG excursions was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the 6-month period and adequate contrasts at Week 26.

5. Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia) [First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)]

   Percentage of participants with at least one treatment emergent hypoglycemia reported at any time of the day 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. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=70 mg/dL (3.9 mmol/L). Hypoglycemic episodes with plasma glucose of 54 mg/dL (<3.0 mmol/L) were also analyzed.

6. Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions [First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)]

   Percentage of participants with hypersensitivity reactions and injection site reactions were reported.

7. Percentage of Participants With Treatment-Emergent Anti-insulin Antibodies (AIAs) [First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)]

   Participants with treatment-emergent AIA (incidence) were reported (as participants with treatment-boosted or treatment-induced AIAs). Participants with treatment-induced AIAs were participants 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). Participants with treatment-boosted AIAs were 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).

Other Outcome Measures

1. Change in Daily Insulin Dose From Baseline to Week 26 [Baseline, Week 26]

   Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Participants with T2DM diagnosed for at least 12 months and treated with insulin glargine and Humalog®/Liprolog® or NovoLog®/NovoRapid® (at least 3 times daily, before each meal) in the 6 months prior to the screening visit.

• Signed written informed consent.

Exclusion criteria:

• At screening visit, age under legal age of adulthood.

• HbA1c <6.5% or >10.0% at screening.

• Diabetes other than T2DM.

• Pregnancy and lactation.

• Women of childbearing potential not protected by highly effective contraceptive method of birth control.

• Use of insulin pump in the 6 months before screening visit.

• Use of insulin other than insulin glargine and Humalog or NovoLog/NovoRapid in the 6 months prior to screening visit. Liprolog® is an European Union (EU) approved insulin lispro and is allowed in those countries where it is marketed.

• Use of Humalog/Liprolog or Novolog/NovoRapid less than 3 times daily, before each meal.

• Use of non-injectable peptides (eg, Glucagon-like peptide-1 (GLP-1) receptor-agonists or other peptides) in the 6 months prior to screening visit.

• Body mass index (BMI) >=40kg/m² at screening visit.

• Hospitalization for diabetic ketoacidosis in the last 6 months before screening visit.

• Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (eg, laser, surgical treatment, or injectable drugs) during the study period.

• The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840217	Foley	Alabama	United States	36535
2	Investigational Site Number 840237	Muscle Shoals	Alabama	United States	35661
3	Investigational Site Number 840245	Chandler	Arizona	United States
4	Investigational Site Number 840219	Phoenix	Arizona	United States	85028
5	Investigational Site Number 840227	Phoenix	Arizona	United States	85050
6	Investigational Site Number 840212	Little Rock	Arkansas	United States	72205
7	Investigational Site Number 840241	El Cajon	California	United States	92020
8	Investigational Site Number 840238	Fresno	California	United States	93720
9	Investigational Site Number 840229	Greenbrae	California	United States	94904
10	Investigational Site Number 840231	Huntington Beach	California	United States	92648
11	Investigational Site Number 840247	Long Beach	California	United States	90807
12	Investigational Site Number 840234	Los Angeles	California	United States	90057
13	Investigational Site Number 840235	Northridge	California	United States	91325
14	Investigational Site Number 840251	Palm Springs	California	United States	92262
15	Investigational Site Number 840249	Santa Ana	California	United States	92704
16	Investigational Site Number 840223	Temecula	California	United States	92591
17	Investigational Site Number 840259	Tustin	California	United States	92780
18	Investigational Site Number 840240	Walnut Creek	California	United States	94598
19	Investigational Site Number 840214	Boynton Beach	Florida	United States	33472
20	Investigational Site Number 840246	Miami	Florida	United States	33176
21	Investigational Site Number 840226	New Port Richey	Florida	United States	34652
22	Investigational Site Number 840205	Ocoee	Florida	United States	34761
23	Investigational Site Number 840206	Palm Harbor	Florida	United States	34684
24	Investigational Site Number 840242	Port Charlotte	Florida	United States	33952
25	Investigational Site Number 840253	Lawrenceville	Georgia	United States	30046
26	Investigational Site Number 840207	Stockbridge	Georgia	United States	30281
27	Investigational Site Number 840248	Arlington Heights	Illinois	United States	60005
28	Investigational Site Number 840204	Avon	Indiana	United States	46123
29	Investigational Site Number 840257	Evansville	Indiana	United States	47714
30	Investigational Site Number 840230	Des Moines	Iowa	United States	50314
31	Investigational Site Number 840239	Rockville	Maryland	United States	20852
32	Investigational Site Number 840236	Troy	Michigan	United States	48085
33	Investigational Site Number 840216	Lincoln	Nebraska	United States	68521
34	Investigational Site Number 840220	Las Vegas	Nevada	United States	89119
35	Investigational Site Number 840233	Las Vegas	Nevada	United States	89148
36	Investigational Site Number 840224	Linden	New Jersey	United States
37	Investigational Site Number 840232	Greensboro	North Carolina	United States	27408
38	Investigational Site Number 840211	Morehead City	North Carolina	United States	28557
39	Investigational Site Number 840228	Morganton	North Carolina	United States	28655
40	Investigational Site Number 840225	Fargo	North Dakota	United States	58103
41	Investigational Site Number 840221	Columbus	Ohio	United States	43201
42	Investigational Site Number 840255	Dayton	Ohio	United States	45439
43	Investigational Site Number 840250	Tipton	Pennsylvania	United States	16684
44	Investigational Site Number 840243	Uniontown	Pennsylvania	United States	15401
45	Investigational Site Number 840208	Chattanooga	Tennessee	United States	37404
46	Investigational Site Number 840215	Jackson	Tennessee	United States	38305
47	Investigational Site Number 840203	Austin	Texas	United States	78731
48	Investigational Site Number 840258	Dallas	Texas	United States	75231
49	Investigational Site Number 840201	Dallas	Texas	United States	75246
50	Investigational Site Number 840222	Renton	Washington	United States	98055
51	Investigational Site Number 840209	Milwaukee	Wisconsin	United States	53209-0996
52	Investigational Site Number 032201	Caba		Argentina	C1425AGC
53	Investigational Site Number 032206	Capital Federal		Argentina	C1056ABJ
54	Investigational Site Number 032202	Capital Federal		Argentina	C1179AAB
55	Investigational Site Number 032205	Ciudad Autonoma De Buenos Aire		Argentina
56	Investigational Site Number 032203	Salta		Argentina	4400
57	Investigational Site Number 152202	Santiago		Chile	7500347
58	Investigational Site Number 152204	Santiago		Chile	7500347
59	Investigational Site Number 152201	Santiago		Chile	7500710
60	Investigational Site Number 170203	Armenia		Colombia	630004
61	Investigational Site Number 276201	Berlin		Germany	10115
62	Investigational Site Number 276204	Heidelberg		Germany	69115
63	Investigational Site Number 276202	Neumünster		Germany	24534
64	Investigational Site Number 276206	Potsdam		Germany	14469
65	Investigational Site Number 276205	Stuttgart		Germany	70378
66	Investigational Site Number 276203	Sulzbach-Rosenberg		Germany	92237
67	Investigational Site Number 348205	Budapest		Hungary	1036
68	Investigational Site Number 348202	Budapest		Hungary	1135
69	Investigational Site Number 348204	Debrecen		Hungary	4032
70	Investigational Site Number 348208	Komárom		Hungary	2900
71	Investigational Site Number 348210	Nagykanizsa		Hungary	8800
72	Investigational Site Number 348203	Szolnok		Hungary	5004
73	Investigational Site Number 348209	Sátoraljaújhely		Hungary	3980
74	Investigational Site Number 380203	Bologna		Italy	40138
75	Investigational Site Number 380201	Milano		Italy	20132
76	Investigational Site Number 380204	Roma		Italy	00133
77	Investigational Site Number 380202	Sesto San Giovanni		Italy	20099
78	Investigational Site Number 410202	Seoul		Korea, Republic of	110-746
79	Investigational Site Number 410204	Seoul		Korea, Republic of	130-872
80	Investigational Site Number 410205	Seoul		Korea, Republic of	139-872
81	Investigational Site Number 410201	Wonju		Korea, Republic of	220-701
82	Investigational Site Number 642210	Bacau		Romania	600154
83	Investigational Site Number 642201	Bucuresti		Romania	020042
84	Investigational Site Number 642202	Bucuresti		Romania	020042
85	Investigational Site Number 642206	Cluj Napoca		Romania	400006
86	Investigational Site Number 642204	Deva		Romania	330084
87	Investigational Site Number 642205	Oradea		Romania	410159
88	Investigational Site Number 642209	Sibiu		Romania	550371
89	Investigational Site Number 642207	Targu Mures		Romania	540142
90	Investigational Site Number 642208	Targu Mures		Romania	540142
91	Investigational Site Number 642203	Timisoara		Romania	300456
92	Investigational Site Number 643201	Saint-Petersburg		Russian Federation	190013
93	Investigational Site Number 643205	Saratov		Russian Federation	410030
94	Investigational Site Number 643203	St-Petersburg		Russian Federation	194354
95	Investigational Site Number 643202	St-Petersburg		Russian Federation	195257
96	Investigational Site Number 643204	St. Petersburg		Russian Federation	194358
97	Investigational Site Number 724201	Barcelona		Spain	08035
98	Investigational Site Number 724203	Málaga		Spain	29010
99	Investigational Site Number 724202	Palma De Mallorca		Spain	07010
100	Investigational Site Number 792201	Istanbul		Turkey	34303
101	Investigational Site Number 792202	Istanbul		Turkey	34890
102	Investigational Site Number 792204	Izmir		Turkey	35100
103	Investigational Site Number 792203	Izmir		Turkey	35340

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02294474
• Other Study ID Numbers: EFC13403; 2014-002844-42; U1111-1156-4296
• First Posted: Nov 19, 2014
• Last Update Posted: Jan 18, 2018
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro

Study Results

Participant Flow

Recruitment Details	The study was conducted at 103 centers in 12 countries. A total of 707 participants were screened between 14 January 2015 and 24 July 2015, of which 202 were screen failures. Screen failures were mainly due to glycated hemoglobin (HbA1c) level <6.5% or >10% at screening visit.
Pre-assignment Detail	A total of 505 participants were randomized and treated in the study. Randomization was stratified by HbA1c at the screening visit (<8%, >=8%) and prior use of Humalog (Yes, No). Assignment to arms was done centrally using interactive voice/web response system in 1:1 ratio (SAR342434: Humalog).

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Period Title: Overall Study
STARTED	253	252
COMPLETED	228	230
NOT COMPLETED	25	22

Baseline Characteristics

Arm/Group Title	SAR342434	Humalog	Total
Arm/Group Description	SAR342434 100 U/mL subcutaneous (SC) injection before meals intake on top of once daily (QD) Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Total of all reporting groups
Overall Participants	253	252	505
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.1 (9.4)	62.8 (8.9)	62.5 (9.1)
Sex: Female, Male (Count of Participants)
Female	117 46.2%	120 47.6%	237 46.9%
Male	136 53.8%	132 52.4%	268 53.1%
Previous meal time insulin (Count of Participants)
Humalog/Liprolog	133 52.6%	126 50%	259 51.3%
NovoLog/NovoRapid	119 47%	124 49.2%	243 48.1%
Both Humalog/Liprolog and NovoLog/NovoRapid	1 0.4%	1 0.4%	2 0.4%
None of the above	0 0%	1 0.4%	1 0.2%
Randomization Strata of Screening HbA1c (Count of Participants)
<8 %	105 41.5%	104 41.3%	209 41.4%
>=8 %	148 58.5%	148 58.7%	296 58.6%
Body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.3 (4.8)	32.1 (4.8)	32.2 (4.8)
Duration of type 2 diabetes mellitus (T2DM) (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16.6 (7.93)	17.52 (8.67)	17.06 (8.31)
HbA1c % (percentage of hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of hemoglobin]	8 (0.86)	8.03 (0.91)	8.01 (0.89)
Average Daily Basal Insulin Dose (U/kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/kg]	0.477 (0.265)	0.458 (0.239)	0.467 (0.252)
Average Daily Mealtime Insulin Dose (U/kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/kg]	0.449 (0.294)	0.433 (0.315)	0.441 (0.305)
Average Daily Total Insulin Dose (U/kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/kg]	0.927 (0.47)	0.888 (0.449)	0.907 (0.459)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to Week 26
Description	Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 6-month period and adequate contrasts at Week 26.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on intent-to-treat (ITT) population that included all randomized participants, irrespective of compliance with the study protocol and procedures. Here, number of participants analyzed = participants with at least one post-baseline HbA1c assessment during the 6-month study period.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	239	246
Least Squares Mean (Standard Error) [percentage of HbA1c]	-0.92 (0.051)	-0.85 (0.051)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAR342434, Humalog
	Comments	Analysis was performed using a MMRM approach with treatment groups, randomization strata, visit (Week 12, Week 26) and treatment-by-visit interaction as fixed categorical effects and baseline HbA1c value and baseline HbA1c value-by-visit interaction as continuous fixed covariates. An unstructured correlation matrix was used to model within-participant errors.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of SAR342434 over Humalog was demonstrated if upper bound of 2-sided 95% confidence interval(CI) of difference between SAR342434 & Humalog was <0.3%.Inverse non-inferiority of Humalog over SAR342434 was tested using hierarchical step-down testing procedure: if non-inferiority of SAR342434 over Humalog was demonstrated,then inverse non-inferiority of Humalog over SAR342434 was tested and demonstrated if lower bound of 2-sided 95% CI of difference between SAR342434 & Humalog>-0.3%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Square (LS) Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.215 to 0.067
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.072
	Estimation Comments	SAR342434 vs. Humalog

2. Secondary Outcome

Title	Percentage of Participants With HbA1c <7.0% and <=6.5% at Week 26
Description	Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	253	252
HbA1c <7.0%	42.3 16.7%	40.5 16.1%
HbA1c<=6.5%	27.3 10.8%	24.2 9.6%

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Description	Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM approach to account for missing data, using all post-baseline FPG data available during the 6-month period and adequate contrasts at Week 26.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, number of participants analyzed = participants with at least one post-baseline FPG assessment during the 6-months study period.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	228	235
Least Squares Mean (Standard Error) [mmol/L]	-0.62 (0.176)	-0.67 (0.176)

4. Secondary Outcome

Title	Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to Week 26
Description	The 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. 7-point SMPGs were performed at least two times in a week before baseline, before visit Week 12 and before visit Week 26. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in the week before a visit. Change in mean 24-hour plasma glucose concentration was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during 6-month period and adequate contrasts at Week 26.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, number of participants analyzed = participants with at least one post-baseline mean 24-hour plasma glucose concentration assessment during 6-month study period.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	201	210
Least Squares Mean (Standard Error) [mmol/L]	-1 (0.137)	-0.91 (0.133)

5. Secondary Outcome

Title	Change in Post Prandial Glucose (PPG) Excursion From Baseline to Week 26
Description	Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour postprandial glucose (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 average across the profiles performed in the week before the visit. Change in PPG excursions was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the 6-month period and adequate contrasts at Week 26.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, number analyzed in each row = participants with at least one post-baseline data during the 6-month period for specified categories.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	253	252
At breakfast	-0.72 (0.236)	-0.23 (0.228)
At lunch	0.06 (0.255)	0.11 (0.25)
At dinner	0.11 (0.264)	-0.1 (0.264)

6. Secondary Outcome

Title	Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia)
Description	Percentage of participants with at least one treatment emergent hypoglycemia reported at any time of the day 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. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=70 mg/dL (3.9 mmol/L). Hypoglycemic episodes with plasma glucose of 54 mg/dL (<3.0 mmol/L) were also analyzed.
Time Frame	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population that included all participants randomized and exposed to at least 1 dose of investigational medicinal product (IMP) (SAR342434 or Humalog), regardless of the amount of treatment administered.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	253	252
Any hypoglycemia	68.4 27%	74.6 29.6%
Severe hypoglycemia	2.4 0.9%	1.6 0.6%
Documented Symptomatic Hypoglycemia (<=3.9mmol/L)	60.1 23.8%	66.3 26.3%
Documented Symptomatic Hypoglycemia (<3.0mmol/L)	28.9 11.4%	27.4 10.9%

7. Secondary Outcome

Title	Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions
Description	Percentage of participants with hypersensitivity reactions and injection site reactions were reported.
Time Frame	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	253	252
Any hypersensitivity reactions	4 1.6%	3.6 1.4%
Any injection site reactions	0.4 0.2%	1.6 0.6%

8. Secondary Outcome

Title	Percentage of Participants With Treatment-Emergent Anti-insulin Antibodies (AIAs)
Description	Participants with treatment-emergent AIA (incidence) were reported (as participants with treatment-boosted or treatment-induced AIAs). Participants with treatment-induced AIAs were participants 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). Participants with treatment-boosted AIAs were 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).
Time Frame	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on anti-insulin antibody population that included all participants from the safety population with at least one AIA sample available for analysis during the 6-months on-treatment period.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	245	248
Number [percentage of participants]	18.8 7.4%	14.5 5.8%

9. Other Pre-specified Outcome

Title	Change in Daily Insulin Dose From Baseline to Week 26
Description	Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 value.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, number analyzed in each row = participants with available data for specified categories.

Arm/Group Title	SAR342434	Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.	Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
Measure Participants	253	252
Basal insulin	0.082 (0.133)	0.071 (0.122)
Mealtime insulin	0.087 (0.209)	0.08 (0.248)
Total insulin	0.172 (0.296)	0.151 (0.297)

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 183) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs and deaths are treatment-emergent adverse events that is AEs that developed, worsened or became serious during the 'on treatment period' (time from first injection of IMP up to 1 day after the last injection of IMP).
Arm/Group Title	SAR342434		Humalog
Arm/Group Description	SAR342434 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.		Humalog 100 U/mL SC injection before meals intake on top of QD Insulin Glargine, up to Week 26.
All Cause Mortality
	SAR342434		Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/253 (0.4%)		2/252 (0.8%)
Serious Adverse Events
	SAR342434		Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/253 (5.5%)		27/252 (10.7%)
Cardiac disorders
Angina pectoris	0/253 (0%)		3/252 (1.2%)
Atrial fibrillation	0/253 (0%)		2/252 (0.8%)
Bundle branch block left	0/253 (0%)		1/252 (0.4%)
Cardiac failure	0/253 (0%)		1/252 (0.4%)
Cardiac failure chronic	1/253 (0.4%)		0/252 (0%)
Cardiac failure congestive	1/253 (0.4%)		2/252 (0.8%)
Cardio-respiratory arrest	1/253 (0.4%)		0/252 (0%)
Cardiopulmonary failure	0/253 (0%)		1/252 (0.4%)
Coronary artery disease	0/253 (0%)		1/252 (0.4%)
Ischaemic cardiomyopathy	1/253 (0.4%)		0/252 (0%)
Myocardial infarction	0/253 (0%)		1/252 (0.4%)
Sinus bradycardia	0/253 (0%)		1/252 (0.4%)
Ear and labyrinth disorders
Vertigo positional	1/253 (0.4%)		0/252 (0%)
Eye disorders
Cataract	1/253 (0.4%)		0/252 (0%)
Vitreous haemorrhage	1/253 (0.4%)		0/252 (0%)
Gastrointestinal disorders
Gastritis erosive	0/253 (0%)		1/252 (0.4%)
Intestinal perforation	0/253 (0%)		1/252 (0.4%)
Pancreatitis	2/253 (0.8%)		0/252 (0%)
General disorders
Non-cardiac chest pain	0/253 (0%)		1/252 (0.4%)
Hepatobiliary disorders
Bile duct stone	0/253 (0%)		1/252 (0.4%)
Infections and infestations
Pneumonia	2/253 (0.8%)		1/252 (0.4%)
Urinary tract infection	0/253 (0%)		1/252 (0.4%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/253 (0%)		1/252 (0.4%)
Hypoglycaemia	0/253 (0%)		2/252 (0.8%)
Hypokalaemia	0/253 (0%)		1/252 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	0/253 (0%)		1/252 (0.4%)
Cervical spinal stenosis	0/253 (0%)		1/252 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/253 (0%)		1/252 (0.4%)
Bladder transitional cell carcinoma	1/253 (0.4%)		0/252 (0%)
Metastatic carcinoma of the bladder	0/253 (0%)		1/252 (0.4%)
Pancreatic carcinoma	0/253 (0%)		1/252 (0.4%)
Nervous system disorders
Carpal tunnel syndrome	1/253 (0.4%)		0/252 (0%)
Cerebrovascular accident	0/253 (0%)		1/252 (0.4%)
Gliosis	1/253 (0.4%)		0/252 (0%)
Hypoglycaemic unconsciousness	2/253 (0.8%)		0/252 (0%)
Syncope	0/253 (0%)		1/252 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/253 (0.4%)		0/252 (0%)
Pulmonary embolism	0/253 (0%)		1/252 (0.4%)
Respiratory failure	1/253 (0.4%)		0/252 (0%)
Vascular disorders
Deep vein thrombosis	0/253 (0%)		1/252 (0.4%)
Hypotension	0/253 (0%)		1/252 (0.4%)
Other (Not Including Serious) Adverse Events
	SAR342434		Humalog
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/253 (0%)		0/252 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.