Trial Outcomes & Findings for A Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo Versus Lantus in Patients With Type 1 Diabetes Mellitus (NCT NCT02688933)

Last Updated: 2022-03-28

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

638 participants

Primary outcome timeframe

During Week 15 and/or 16

Results posted on

2022-03-28

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	320	318
Overall Study COMPLETED	291	281
Overall Study NOT COMPLETED	29	37

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	3	1
Overall Study Lack of Efficacy	2	2
Overall Study Poor compliance to protocol	7	4
Overall Study Hypoglycemia	2	0
Overall Study Other than Specified	14	25
Overall Study Lost to Follow-up	1	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HOE901-U300 n=320 Participants 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 n=318 Participants 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 n=638 Participants Total of all reporting groups
Age, Continuous	45.5 years STANDARD_DEVIATION 14.0 • n=5 Participants	45.5 years STANDARD_DEVIATION 13.9 • n=7 Participants	45.5 years STANDARD_DEVIATION 13.9 • n=5 Participants
Sex: Female, Male Female	140 Participants n=5 Participants	138 Participants n=7 Participants	278 Participants n=5 Participants
Sex: Female, Male Male	180 Participants n=5 Participants	180 Participants n=7 Participants	360 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	43 Participants n=5 Participants	42 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	277 Participants n=5 Participants	276 Participants n=7 Participants	553 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	24 Participants n=5 Participants	28 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) White	281 Participants n=5 Participants	282 Participants n=7 Participants	563 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Body mass index	27.50 kg/m^2 STANDARD_DEVIATION 4.88 • n=5 Participants	27.65 kg/m^2 STANDARD_DEVIATION 4.92 • n=7 Participants	27.57 kg/m^2 STANDARD_DEVIATION 4.90 • n=5 Participants

PRIMARY outcome

Timeframe: During Week 15 and/or 16

Population: 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).

Outcome measures

Outcome measures
Measure	HOE901-U300 n=277 Participants 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 n=268 Participants 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.
Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM	55.40 percentage of time Standard Error 1.08	55.18 percentage of time Standard Error 1.10

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: mITT population.

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).

Outcome measures

Outcome measures
Measure	HOE901-U300 n=277 Participants 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 n=268 Participants 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.
Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia Documented <=70mg/dL	70.8 percentage of participants	68.3 percentage of participants
Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia Documented <54 mg/dL	50.9 percentage of participants	54.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: mITT population.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=277 Participants 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 n=268 Participants 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.
Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year Documented <=70 mg/dL	11.38 events per participant-year	11.39 events per participant-year
Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year Documented <54 mg/dL	4.99 events per participant-year	5.61 events per participant-year

SECONDARY outcome

Timeframe: Baseline, during Week 15 and/or Week 16

Population: mITT population.

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).

Outcome measures

Outcome measures
Measure	HOE901-U300 n=277 Participants 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 n=268 Participants 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.
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	-1.99 mg/dL Standard Error 3.68	5.67 mg/dL Standard Error 3.72

SECONDARY outcome

Timeframe: During Week 15 and/or Week 16

Population: mITT population

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).

Outcome measures

Outcome measures
Measure	HOE901-U300 n=277 Participants 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 n=268 Participants 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.
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	36.49 percentage of time Standard Error 1.62	35.07 percentage of time Standard Error 1.65

SECONDARY outcome

Timeframe: During Week 15 and/or Week 16

Population: mITT population.

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.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=277 Participants 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 n=268 Participants 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.
Coefficient of Variation (CV%) in Mean CGM Glucose Total CV%	41.27 percent of mean glucose level Standard Error 0.63	40.72 percent of mean glucose level Standard Error 0.64
Coefficient of Variation (CV%) in Mean CGM Glucose Within-day CV%	36.99 percent of mean glucose level Standard Error 0.56	36.23 percent of mean glucose level Standard Error 0.56
Coefficient of Variation (CV%) in Mean CGM Glucose Between-days CV%	17.44 percent of mean glucose level Standard Error 0.59	17.53 percent of mean glucose level Standard Error 0.60

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: 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.

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

Outcome measures

Outcome measures
Measure	HOE901-U300 n=320 Participants 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 n=318 Participants 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.
Change From Baseline in Daily Insulin Dose at Week 16 Daily basal Insulin Dose	8.8 International Units Standard Deviation 11.8	7.0 International Units Standard Deviation 10.1
Change From Baseline in Daily Insulin Dose at Week 16 Daily bolus Insulin Dose	-1.8 International Units Standard Deviation 11.8	-3.0 International Units Standard Deviation 11.3

POST_HOC outcome

Timeframe: Baseline, during Week 15 and/or Week 16

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

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.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=277 Participants 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 n=268 Participants 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.
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 End of study HbA1c <7.5%	105.84 minutes Standard Error 25.64	56.07 minutes Standard Error 25.40
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 End of study HbA1c >=7.5%	11.64 minutes Standard Error 27.26	31.95 minutes Standard Error 27.57

Adverse Events

HOE901-U300

Serious events: 17 serious events

Other events: 54 other events

Deaths: 0 deaths

Lantus

Serious events: 14 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	HOE901-U300 n=320 participants at risk 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 n=318 participants at risk 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.
Infections and infestations Nasopharyngitis	8.4% 27/320 • 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. 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).	8.5% 27/318 • 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. 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).
Infections and infestations Upper respiratory tract infection	8.8% 28/320 • 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. 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).	8.8% 28/318 • 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. 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).

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER