A Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo Versus Lantus in Patients With Type 1 Diabetes Mellitus

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02688933
• Collaborator: (none)
• Enrollment: 638
• Locations: 100
• Arms: 2
• Actual Duration (Months): 13.5
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate that morning injection of Toujeo (HOE901-U300) compared to Lantus provides better glycemic control evaluated by Continuous Glucose Monitoring (CGM) in adult participants with type 1 diabetes mellitus.

Secondary Objective:

To demonstrate that treatment with HOE901-U300 compared to Lantus provides:

• Lower incidence rate of nocturnal symptomatic hypoglycemia;

• Better glucose control coverage during the last hours of CGM before next basal-insulin dosing;

• Less variability in CGM profile.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus	Drug: HOE901-U300 (Insulin Glargine 300 U/ml); Drug: Lantus (Insulin Glargine 100 U/ml); Drug: Mandated back ground therapy	Phase 4

Detailed Description

The maximum study duration per participant was to be of approximately 20 weeks that consisted of an up to a 4-week screening and CGM training period including a 1-2 week baseline (blinded) CGM performance (allowed for re-training), a 14-week open-label, comparative treatment period allowing for dose titration in both basal and meal-time insulin and including a 1-2 week end-of treatment blinded CGM collection with fixed dose of HOE901-U300 and Lantus, and a 2 day post treatment follow-up period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 638 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Active-controlled, Parallel Group, 16-Week Open Label Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo (Insulin Glargine-U300) Versus Lantus in Patients With Type 1 Diabetes Mellitus
• Actual Study Start Date: May 5, 2016
• Actual Primary Completion Date: Jun 19, 2017
• Actual Study Completion Date: Jun 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HOE901-U300 HOE901-U300 (Insulin glargine, 300 U/mL) once daily for 16 weeks on top of mealtime insulins analogs. Basal insulin doses were individually titrated (until the end of Week 14) to reach fasting self-measured plasma glucose (SMPG) levels of 80 to 100 mg/dL, while mitigating hypoglycemia.	Drug: HOE901-U300 (Insulin Glargine 300 U/ml); Self-administered by subcutaneous (SC) injection in the morning (between waking up and breakfast) using a pre-filled pen.; Other Names: Toujeo ; Drug: Mandated back ground therapy; Rapid insulin analogs: e.g., insulin glulisine, insulin lispro or insulin aspart, used by participant at least 30 days before screening. Mealtime insulin was to be continued during the study and titrated towards protocol specified postprandial glucose targets (130-180 mg/dL).
Active Comparator: Lantus Lantus (Insulin glargine, 100 U/mL) once daily for 16 weeks on top of mealtime insulins analogs. Basal insulin doses were individually titrated (until the end of Week 14) to reach fasting SMPG levels of 80 to 100 mg/dL, while mitigating hypoglycemia.	Drug: Lantus (Insulin Glargine 100 U/ml); Self-administered by subcutaneous (SC) injection in the morning (between waking up and breakfast using a pre-filled pen.; Other Names: HOE901-U100 ; Drug: Mandated back ground therapy; Rapid insulin analogs: e.g., insulin glulisine, insulin lispro or insulin aspart, used by participant at least 30 days before screening. Mealtime insulin was to be continued during the study and titrated towards protocol specified postprandial glucose targets (130-180 mg/dL).

Outcome Measures

Primary Outcome Measures

1. Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM [During Week 15 and/or 16]

   The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained from a generalized linear model with identity link including post baseline CGM assessment during Week 15 (and/or Week 16).

Secondary Outcome Measures

1. Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia [Baseline up to Week 16]

   Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia electronic case report form (eCRF).

2. Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year [Baseline up to Week 16]

   Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia eCRF.

3. Mean Change From Baseline in Glucose Level During Last 4 Hours of CGM Data Collection Prior to the Next Day Basal Insulin Injection During Week 15 and/or Week 16 [Baseline, during Week 15 and/or Week 16]

   Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16).

4. Percentage of Time Glucose Concentrations Within the Target Range of 70 to 140 mg/dL During Last 4 Hours of CGM Data Collection Prior to Next Day Basal Insulin Injection [During Week 15 and/or Week 16]

   Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16).

5. Coefficient of Variation (CV%) in Mean CGM Glucose [During Week 15 and/or Week 16]

   CV% was a measure of spread of variability relative to mean of population. For CGM glucose values over 24 hours, CV% was measure of glycemic variability across 24-hour day and calculated for each period (total, within day and between days) as ratio of standard deviation of glucose values to mean of glucose values.

Other Outcome Measures

1. Change From Baseline in Daily Insulin Dose at Week 16 [Baseline, Week 16]

   Change from Baseline at Week 16 for daily basal insulin dose and daily bolus insulin dose was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Adult participants (male and female) with type 1 diabetes mellitus (T1DM).

• Signed written informed consent.

Exclusion criteria:

• Age <18 years or >70 years.

• Fasting c-peptide ≥0.3 nmol/L as per source document or central lab test at Visit 1.

• Glycated hemoglobin (HbA1c) ≤ 6.5 % or ≥ 10.0% via central lab test at Visit 1.

• Participants who experienced none of episode of documented symptomatic and/or severe hypoglycemia (as per the American Diabetes Association (ADA) classification) during the past month prior to screening.

• Participants who experienced >1 episode of severe hypoglycemia resulting in coma/seizures during the last 12 months before screening.

• Participants received less than 1 year treatment with basal plus mealtime insulin.

• Used any basal insulins other than long-acting insulin analogs (ie, Lantus, Toujeo, Levemir, and Tresiba) in the past 3 months before screening.

• Required >80 U/day basal insulin analogs or not on stable dose (±20% total dose) within 30 days prior to screening.

• Used fewer than 2 injections of rapid-acting insulin analog per day within 30 days prior to screening.

• Used human regular insulin as mealtime insulin within 30 days prior to screening.

• Used an insulin pump during the last 6 months before screening.

• History of unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to required treatment (e.g., laser, surgical treatment, or injectable drugs) during the study period.

• Pregnant or breast-feeding women or planned pregnancy during the duration of the study.

• Use of any other investigational drug(s) within 1 month or 5 half-lives, whichever was longer prior to screening.

• Inappropriate CGM use during screening period evidenced by failure to obtain a minimum of 4 days of usable records by the end of screening.

• Noncompliance with self-monitored plasma glucose (SMPG) performance evidenced by failure to demonstrate at least 5 days of 5 point SMPG records by the end of screening.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840-151	Little Rock	Arkansas	United States	72205
2	Investigational Site Number 840-071	Concord	California	United States	94520-2270
3	Investigational Site Number 840-149	Escondido	California	United States	92025
4	Investigational Site Number 840-004	Fresno	California	United States	93720
5	Investigational Site Number 840-110	Greenbrae	California	United States	94904
6	Investigational Site Number 840-124	La Jolla	California	United States	92037
7	Investigational Site Number 840-030	La Mesa	California	United States	91942
8	Investigational Site Number 840-044	Los Angeles	California	United States	90036
9	Investigational Site Number 840-022	Los Angeles	California	United States	90057
10	Investigational Site Number 840-129	Los Gatos	California	United States	95032
11	Investigational Site Number 840-024	Northridge	California	United States	91325
12	Investigational Site Number 840-069	Pomona	California	United States	91766
13	Investigational Site Number 840-090	Pomona	California	United States	91767
14	Investigational Site Number 840-132	Rolling Hills Estates	California	United States	90274
15	Investigational Site Number 840-130	San Jose	California	United States	95148
16	Investigational Site Number 840-055	San Ramon	California	United States	94583
17	Investigational Site Number 840-028	Santa Barbara	California	United States
18	Investigational Site Number 840-063	Tarzana	California	United States	91356
19	Investigational Site Number 840-138	Tustin	California	United States	92780-6953
20	Investigational Site Number 840-016	Ventura	California	United States	93003
21	Investigational Site Number 840-039	Denver	Colorado	United States	80209
22	Investigational Site Number 840-021	Denver	Colorado	United States	80246
23	Investigational Site Number 840-070	Denver	Colorado	United States	80262
24	Investigational Site Number 840-046	Englewood	Colorado	United States	80113
25	Investigational Site Number 840-072	Coral Gables	Florida	United States	33124
26	Investigational Site Number 840-133	Hialeah	Florida	United States	33016
27	Investigational Site Number 840-137	Maitland	Florida	United States	32751
28	Investigational Site Number 840-049	Miami	Florida	United States	33155
29	Investigational Site Number 840-076	Miami	Florida	United States	33176
30	Investigational Site Number 840-023	New Port Richey	Florida	United States	34652
31	Investigational Site Number 840-053	Ocoee	Florida	United States	34761
32	Investigational Site Number 840-112	Ormond Beach	Florida	United States	32174
33	Investigational Site Number 840-018	Palm Harbor	Florida	United States	34684
34	Investigational Site Number 840-047	Port Charlotte	Florida	United States	33952
35	Investigational Site Number 840-114	Tampa	Florida	United States	33612
36	Investigational Site Number 840-036	West Palm Beach	Florida	United States	33401
37	Investigational Site Number 840-001	Atlanta	Georgia	United States	30318
38	Investigational Site Number 840-064	Columbus	Georgia	United States	31904
39	Investigational Site Number 840-012	Lawrenceville	Georgia	United States	30046
40	Investigational Site Number 840-008	Roswell	Georgia	United States	30076
41	Investigational Site Number 840-014	Stockbridge	Georgia	United States	30281
42	Investigational Site Number 840-060	Idaho Falls	Idaho	United States	83404
43	Investigational Site Number 840-125	Arlington Heights	Illinois	United States	60005
44	Investigational Site Number 840-011	Chicago	Illinois	United States	60612
45	Investigational Site Number 840-134	Crystal Lake	Illinois	United States	60012
46	Investigational Site Number 840-002	West Des Moines	Iowa	United States	50265
47	Investigational Site Number 840-073	Wichita	Kansas	United States	67226
48	Investigational Site Number 840-062	Covington	Kentucky	United States	41011
49	Investigational Site Number 840-042	Lexington	Kentucky	United States	40503
50	Investigational Site Number 840-009	Metairie	Louisiana	United States	70006
51	Investigational Site Number 840-032	New Orleans	Louisiana	United States	70115
52	Investigational Site Number 840-054	Hyattsville	Maryland	United States	20782
53	Investigational Site Number 840-006	Rockville	Maryland	United States	20852
54	Investigational Site Number 840-157	Framingham	Massachusetts	United States	01702
55	Investigational Site Number 840-122	Waltham	Massachusetts	United States	02453
56	Investigational Site Number 840-037	Flint	Michigan	United States	48532
57	Investigational Site Number 840-067	Billings	Montana	United States	59101
58	Investigational Site Number 840-094	Lincoln	Nebraska	United States	68526
59	Investigational Site Number 840-033	Omaha	Nebraska	United States	68114
60	Investigational Site Number 840-142	Omaha	Nebraska	United States	68124
61	Investigational Site Number 840-040	Henderson	Nevada	United States	89052
62	Investigational Site Number 840-017	Las Vegas	Nevada	United States	89148
63	Investigational Site Number 840-102	New York	New York	United States	10001
64	Investigational Site Number 840-108	New York	New York	United States	10029
65	Investigational Site Number 840-109	Staten Island	New York	United States	10301-3914
66	Investigational Site Number 840-045	Greenville	North Carolina	United States	27834
67	Investigational Site Number 840-010	Morehead City	North Carolina	United States	28557
68	Investigational Site Number 840-080	Morehead City	North Carolina	United States	28557
69	Investigational Site Number 840-051	Fargo	North Dakota	United States	58103
70	Investigational Site Number 840-123	Columbus	Ohio	United States	43203
71	Investigational Site Number 840-104	Mentor	Ohio	United States	44060
72	Investigational Site Number 840-079	Norman	Oklahoma	United States	73069
73	Investigational Site Number 840-162	Bend	Oregon	United States	97702
74	Investigational Site Number 840-096	Portland	Oregon	United States	97210
75	Investigational Site Number 840-058	Chattanooga	Tennessee	United States	37411
76	Investigational Site Number 840-003	Dallas	Texas	United States	75230
77	Investigational Site Number 840-019	Dallas	Texas	United States	75231
78	Investigational Site Number 840-075	Dallas	Texas	United States	75235
79	Investigational Site Number 840-005	Dallas	Texas	United States	75246
80	Investigational Site Number 840-013	Dallas	Texas	United States	75246
81	Investigational Site Number 840-153	El Paso	Texas	United States	79925
82	Investigational Site Number 840-026	Fort Worth	Texas	United States	76132
83	Investigational Site Number 840-081	Houston	Texas	United States	77024
84	Investigational Site Number 840-160	Houston	Texas	United States	77043
85	Investigational Site Number 840-156	Houston	Texas	United States	77079
86	Investigational Site Number 840-152	Houston	Texas	United States	77089
87	Investigational Site Number 840-031	Houston	Texas	United States	77095
88	Investigational Site Number 840-140	Lufkin	Texas	United States	75904
89	Investigational Site Number 840-029	Mesquite	Texas	United States	75149
90	Investigational Site Number 840-048	North Richland Hills	Texas	United States	76180
91	Investigational Site Number 840-150	Pearland	Texas	United States	77584
92	Investigational Site Number 840-083	Murray	Utah	United States	84123
93	Investigational Site Number 840-101	Ogden	Utah	United States	84405
94	Investigational Site Number 840-097	Salt Lake City	Utah	United States	84102
95	Investigational Site Number 840-143	Bennington	Vermont	United States	05201
96	Investigational Site Number 840-056	Burlington	Vermont	United States	05405
97	Investigational Site Number 840-015	Renton	Washington	United States	98055
98	Investigational Site Number 840-074	Spokane	Washington	United States	99207
99	Investigational Site Number 840-139	Bridgeport	West Virginia	United States	26330
100	Investigational Site Number 840-111	Manati		Puerto Rico	00674

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Aug 2, 2016
• Statistical Analysis Plan - Jul 7, 2017

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02688933
• Other Study ID Numbers: LPS14587; U1111-1176-0936
• First Posted: Feb 23, 2016
• Last Update Posted: Mar 28, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Glargine

Study Results

Participant Flow

Recruitment Details	The study was conducted at 100 sites in United States. A total of 980 participants were screened between 5 May 2016 and 16 February 2017, of whom 342 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Detail	A total of 638 participants were randomized in HOE901-U300 or Lantus, stratified by baseline HbA1c (<8 %,> =8%), frequency of basal insulin injections at Visit 1 (twice vs once daily), current continuous glucose monitoring (CGM) use at Visit 1(yes/no) and mealtime insulin titration algorithm (simple titration vs carbohydrate counting).

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting self-measured plasma glucose (SMPG) levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Period Title: Overall Study
STARTED	320	318
COMPLETED	291	281
NOT COMPLETED	29	37

Baseline Characteristics

Arm/Group Title	HOE901-U300	Lantus	Total
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Total of all reporting groups
Overall Participants	320	318	638
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (14.0)	45.5 (13.9)	45.5 (13.9)
Sex: Female, Male (Count of Participants)
Female	140 43.8%	138 43.4%	278 43.6%
Male	180 56.3%	180 56.6%	360 56.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	43 13.4%	42 13.2%	85 13.3%
Not Hispanic or Latino	277 86.6%	276 86.8%	553 86.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 0.9%	0 0%	3 0.5%
Asian	5 1.6%	3 0.9%	8 1.3%
Native Hawaiian or Other Pacific Islander	1 0.3%	1 0.3%	2 0.3%
Black or African American	24 7.5%	28 8.8%	52 8.2%
White	281 87.8%	282 88.7%	563 88.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 1.9%	4 1.3%	10 1.6%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.50 (4.88)	27.65 (4.92)	27.57 (4.90)

Outcome Measures

1. Primary Outcome

Title	Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM
Description	The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained from a generalized linear model with identity link including post baseline CGM assessment during Week 15 (and/or Week 16).
Time Frame	During Week 15 and/or 16

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population that included all participants who were randomized and had a post-baseline CGM assessment and enough CGM data values to calculate the primary outcome measure, percent of time in range of 70-180 mg/dL during Week 15 (and/or Week 16).

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	277	268
Least Squares Mean (Standard Error) [percentage of time]	55.40 (1.08)	55.18 (1.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HOE901-U300, Lantus
	Comments	Analysis was performed using generalized linear model with identity link, had percentage of time glucose concentration within target range 70-180 mg/dL as dependent variable, treatment group as an independent variable, adjusting variables including baseline characteristics: duration of diabetes, baseline BMI, age, and randomization strata (HbA1c at screening [<8.0% vs ≥8.0%], frequency of Lantus injection at screening, current CGM use [yes/no], and mealtime insulin titration algorithm).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8494
	Comments	Threshold for significance at 0.05 level.
	Method	Generalized linear model
	Comments	Generalized linear model with identity link
Method of Estimation	Estimation Parameter	Least Square mean difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.15
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia
Description	Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia electronic case report form (eCRF).
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	277	268
Documented <=70mg/dL	70.8 22.1%	68.3 21.5%
Documented <54 mg/dL	50.9 15.9%	54.1 17%

3. Secondary Outcome

Title	Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year
Description	Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia eCRF.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	277	268
Documented <=70 mg/dL	11.38	11.39
Documented <54 mg/dL	4.99	5.61

4. Secondary Outcome

Title	Mean Change From Baseline in Glucose Level During Last 4 Hours of CGM Data Collection Prior to the Next Day Basal Insulin Injection During Week 15 and/or Week 16
Description	Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16).
Time Frame	Baseline, during Week 15 and/or Week 16

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	277	268
Least Squares Mean (Standard Error) [mg/dL]	-1.99 (3.68)	5.67 (3.72)

5. Secondary Outcome

Title	Percentage of Time Glucose Concentrations Within the Target Range of 70 to 140 mg/dL During Last 4 Hours of CGM Data Collection Prior to Next Day Basal Insulin Injection
Description	Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16).
Time Frame	During Week 15 and/or Week 16

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	277	268
Least Squares Mean (Standard Error) [percentage of time]	36.49 (1.62)	35.07 (1.65)

6. Secondary Outcome

Title	Coefficient of Variation (CV%) in Mean CGM Glucose
Description	CV% was a measure of spread of variability relative to mean of population. For CGM glucose values over 24 hours, CV% was measure of glycemic variability across 24-hour day and calculated for each period (total, within day and between days) as ratio of standard deviation of glucose values to mean of glucose values.
Time Frame	During Week 15 and/or Week 16

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	277	268
Total CV%	41.27 (0.63)	40.72 (0.64)
Within-day CV%	36.99 (0.56)	36.23 (0.56)
Between-days CV%	17.44 (0.59)	17.53 (0.60)

7. Other Pre-specified Outcome

Title	Change From Baseline in Daily Insulin Dose at Week 16
Description	Change from Baseline at Week 16 for daily basal insulin dose and daily bolus insulin dose was reported.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Safety population: all participants who took at least 1 dose of randomized treatment & analyzed as-treated (as per treatment actually received) also to whom it was unclear whether they took study medication & who received more than 1 study treatment during trial. Here, "number analyzed": number of participants evaluable for each specified category.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	320	318
Daily basal Insulin Dose	8.8 (11.8)	7.0 (10.1)
Daily bolus Insulin Dose	-1.8 (11.8)	-3.0 (11.3)

8. Post-Hoc Outcome

Title	Change From Baseline in Time (Min) of Mean Glucose Concentration Within the Target Range of 70 to 180 mg/dL, by End of Study hbA1c Levels During Week 15 and/or Week 16
Description	Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessments. Data was reported for participants with an end of study HbA1c <7.5 or HbA1c >=7.5% over a 24 hour period.
Time Frame	Baseline, during Week 15 and/or Week 16

Outcome Measure Data

Analysis Population Description

mITT population. Here, "number analyzed" signifies the number of participants evaluable for each specified category.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Measure Participants	277	268
End of study HbA1c <7.5%	105.84 (25.64)	56.07 (25.40)
End of study HbA1c >=7.5%	11.64 (27.26)	31.95 (27.57)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of informed consent form up to study completion (Week 16) regardless of seriousness or relationship to study drug.
Adverse Event Reporting Description	Reported AEs are treatment-emergent AEs developed/worsened during on treatment period (time from first dose of investigational medicinal product [IMP] up to one day after last dose of IMP).
Arm/Group Title	HOE901-U300		Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.		Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
All Cause Mortality
	HOE901-U300		Lantus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/320 (0%)		0/318 (0%)
Serious Adverse Events
	HOE901-U300		Lantus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/320 (5.3%)		14/318 (4.4%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/320 (0.3%)		0/318 (0%)
Cardiac disorders
Cardiac arrest	0/320 (0%)		1/318 (0.3%)
Coronary artery disease	0/320 (0%)		1/318 (0.3%)
Eye disorders
Angle closure glaucoma	1/320 (0.3%)		0/318 (0%)
General disorders
Non-cardiac chest pain	1/320 (0.3%)		0/318 (0%)
Infections and infestations
Diabetic foot infection	0/320 (0%)		1/318 (0.3%)
Gangrene	0/320 (0%)		1/318 (0.3%)
Influenza	1/320 (0.3%)		0/318 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/320 (0%)		3/318 (0.9%)
Fall	0/320 (0%)		1/318 (0.3%)
Intentional overdose	1/320 (0.3%)		0/318 (0%)
Lower limb fracture	1/320 (0.3%)		0/318 (0%)
Rib fracture	0/320 (0%)		1/318 (0.3%)
Road traffic accident	2/320 (0.6%)		1/318 (0.3%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/320 (0.3%)		0/318 (0%)
Hyperglycaemia	2/320 (0.6%)		0/318 (0%)
Hypoglycaemia	2/320 (0.6%)		3/318 (0.9%)
Nervous system disorders
Hypoglycaemic coma	0/320 (0%)		1/318 (0.3%)
Hypoglycaemic encephalopathy	0/320 (0%)		1/318 (0.3%)
Hypoglycaemic seizure	2/320 (0.6%)		3/318 (0.9%)
Hypoglycaemic unconsciousness	6/320 (1.9%)		3/318 (0.9%)
Psychiatric disorders
Depression	1/320 (0.3%)		0/318 (0%)
Renal and urinary disorders
Acute kidney injury	2/320 (0.6%)		0/318 (0%)
Renal injury	1/320 (0.3%)		0/318 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	0/320 (0%)		1/318 (0.3%)
Pneumothorax	0/320 (0%)		1/318 (0.3%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/320 (0%)		1/318 (0.3%)
Subcutaneous emphysema	0/320 (0%)		1/318 (0.3%)
Other (Not Including Serious) Adverse Events
	HOE901-U300		Lantus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/320 (16.9%)		54/318 (17%)
Infections and infestations
Nasopharyngitis	27/320 (8.4%)		27/318 (8.5%)
Upper respiratory tract infection	28/320 (8.8%)		28/318 (8.8%)

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.