A Study Comparing the Efficacy and Safety of the Morning... | NCT02688933

ID	Type	Description	Link
U1111-1176-0936	Other Identifier	UTN

Status Module

Oversight Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
HOE901-U300	Experimental	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) Drug: Mandated back ground therapy
Lantus	Active Comparator	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) Drug: Mandated back ground therapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
HOE901-U300 (Insulin Glargine 300 U/ml)	Drug	Self-administered by subcutaneous (SC) injection in the morning (between waking up and breakfast) using a pre-filled pen.	HOE901-U300

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM	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).	During Week 15 and/or 16

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia	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).	Baseline up to Week 16

Other Outcomes

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

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840-151		Little Rock	Arkansas	72205	United States
Investigational Site Number 840-071

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	HOE901-U300	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.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 2, 2016	Jun 19, 2018

Arm/Group Information

ID	Title	Description
BG000	HOE901-U300	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.
BG001	Lantus	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00045.5± 14.0 BG00145.5± 13.9 BG00245.5± 13.9

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000140 BG001138 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00043 BG00142 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0003 BG0010 BG002

Body mass index

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00027.50± 4.88 BG00127.65± 4.92 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM

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).

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).

Posted

Least Squares Mean

Standard Error

percentage of time

During Week 15 and/or 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts
Participants	OG000277 OG001268

Title

Denominators

Categories

Title	Measurements
	OG00055.40± 1.08 OG00155.18± 1.10

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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).	Generalized linear model	Generalized linear model with identity link	0.8494	Threshold for significance at 0.05 level.	Least Square mean difference	0.22	Standard Error of the Mean	1.15	2-Sided

Secondary

Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia

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).

mITT population.

Posted

Number

percentage of participants

Baseline up to Week 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts
Participants

Secondary

Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year

mITT population.

Posted

Number

events per participant-year

Baseline up to Week 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts
Participants

Secondary

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

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).

mITT population.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, during Week 15 and/or Week 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts
Participants

Secondary

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

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).

mITT population

Posted

Least Squares Mean

Standard Error

percentage of time

During Week 15 and/or Week 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts
Participants

Secondary

Coefficient of Variation (CV%) in Mean CGM Glucose

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.

mITT population.

Posted

Least Squares Mean

Standard Error

percent of mean glucose level

During Week 15 and/or Week 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts
Participants

Other Pre-specified

Change From Baseline in Daily Insulin Dose at Week 16

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

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.

Posted

Mean

Standard Deviation

International Units

Baseline, Week 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts

Post-Hoc

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

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.

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

Posted

Least Squares Mean

Standard Error

minutes

Baseline, during Week 15 and/or Week 16

ID	Title	Description
OG000	HOE901-U300	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.
OG001	Lantus	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.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	HOE901-U300	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.	0	320	17	320	54	320
EG001	Lantus	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.	0	318	14	318	54	318

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diabetic foot infection	Infections and infestations	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Gangrene	Infections and infestations	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Influenza	Infections and infestations	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDra 20.0	Systematic Assessment	EG0002 affected320 at risk EG0010 affected318 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 20.0	Systematic Assessment	EG0002 affected320 at risk EG0013 affected318 at risk
Depression	Psychiatric disorders	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Hypoglycaemic coma	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Hypoglycaemic encephalopathy	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0002 affected320 at risk EG0013 affected318 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDra 20.0	Systematic Assessment	EG0006 affected320 at risk EG0013 affected318 at risk
Angle closure glaucoma	Eye disorders	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Cardiac arrest	Cardiac disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Coronary artery disease	Cardiac disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Subcutaneous emphysema	Skin and subcutaneous tissue disorders	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Acute kidney injury	Renal and urinary disorders	MedDra 20.0	Systematic Assessment	EG0002 affected320 at risk EG0010 affected318 at risk
Renal injury	Renal and urinary disorders	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Non-cardiac chest pain	General disorders	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0013 affected318 at risk
Fall	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0001 affected320 at risk EG0010 affected318 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0000 affected320 at risk EG0011 affected318 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDra 20.0	Systematic Assessment	EG0002 affected320 at risk EG0011 affected318 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nasopharyngitis	Infections and infestations	MedDra 20.0	Systematic Assessment		EG00027 affected320 at risk EG00127 affected318 at risk
Upper respiratory tract infection	Infections and infestations	MedDra 20.0	Systematic Assessment		EG00028 affected320 at risk EG00128 affected318 at risk