Trial Outcomes & Findings for Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 1 Diabetes Mellitus on Basal Plus Mealtime Insulin (NCT NCT01658579)

Results Overview

Percentage of time with glucose within glycemic range (4.4-7.8 mmol/L) was assessed by the total time within glycemic range divided by the length of the assessment interval.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)

Results posted on

2015-06-01

Participant Flow

A total of 85 participants were screened, of whom 26 participants were screen failures and 59 participants were randomized. The data for outcome measures was planned to be reported for combined reporting arms (HOE901-U300 Combined and Lantus Combined).

Participant milestones

Participant milestones
Measure	HOE901-U300 Morning Then Evening HOE901-U300 (new insulin glargine 300 units per milliliter \[U/mL\]) subcutaneous (SC) injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B. Dose titration seeking fasting plasma glucose 4.4-7.2 millimole per liter (mmol/L) (80-130 milligram per deciliter \[mg/dL\]).	HOE901-U300 Evening Then Morning HOE901-U300 SC injection once daily in evening for 8 weeks during treatment period A, followed by once daily in morning for 8 weeks during treatment period B. Dose titration seeking fasting plasma glucose 4.4-7.2 mmol/L (80-130 mg/dL).	Lantus Morning Then Evening Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B. Dose titration seeking fasting plasma glucose 4.4-7.2 mmol/L (80-130 mg/dL).	Lantus Evening Then Morning Lantus SC injection once daily in evening for 8 weeks during treatment period A, followed by once daily in morning for 8 weeks during treatment period B. Dose titration seeking fasting plasma glucose 4.4-7.2 mmol/L (80-130 mg/dL).
Treatment Period A STARTED	15	15	15	14
Treatment Period A COMPLETED	14	15	14	13
Treatment Period A NOT COMPLETED	1	0	1	1
Treatment Period B STARTED	14	15	14	13
Treatment Period B COMPLETED	14	15	14	12
Treatment Period B NOT COMPLETED	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	HOE901-U300 Morning Then Evening HOE901-U300 (new insulin glargine 300 units per milliliter \[U/mL\]) subcutaneous (SC) injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B. Dose titration seeking fasting plasma glucose 4.4-7.2 millimole per liter (mmol/L) (80-130 milligram per deciliter \[mg/dL\]).	Lantus Morning Then Evening Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B. Dose titration seeking fasting plasma glucose 4.4-7.2 mmol/L (80-130 mg/dL).	Lantus Evening Then Morning Lantus SC injection once daily in evening for 8 weeks during treatment period A, followed by once daily in morning for 8 weeks during treatment period B. Dose titration seeking fasting plasma glucose 4.4-7.2 mmol/L (80-130 mg/dL).
Treatment Period A Other	0	1	1
Treatment Period A Adverse Event	1	0	0
Treatment Period B Other	0	0	1

Baseline Characteristics

Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 1 Diabetes Mellitus on Basal Plus Mealtime Insulin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HOE901-U300 Morning Then Evening n=15 Participants HOE901-U300 SC injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B.	HOE901-U300 Evening Then Morning n=15 Participants HOE901-U300 SC injection once daily in evening for 8 weeks during treatment period A, followed by once daily in morning for 8 weeks during treatment period B.	Lantus Morning Then Evening n=15 Participants Lantus SC injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B.	Lantus Evening Then Morning n=14 Participants Lantus SC injection once daily in evening for 8 weeks during treatment period A, followed by once daily in morning for 8 weeks during treatment period B.	Total n=59 Participants Total of all reporting groups
Age, Continuous	43.6 years STANDARD_DEVIATION 14.6 • n=5 Participants	46.2 years STANDARD_DEVIATION 15.9 • n=7 Participants	39.7 years STANDARD_DEVIATION 12.5 • n=5 Participants	47.6 years STANDARD_DEVIATION 14.1 • n=4 Participants	44.2 years STANDARD_DEVIATION 14.3 • n=21 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants	27 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	4 Participants n=4 Participants	32 Participants n=21 Participants
Body Mass Index (BMI)	27.5 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.9 • n=5 Participants	27.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.0 • n=7 Participants	28.3 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.2 • n=5 Participants	26.1 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.1 • n=4 Participants	27.3 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.3 • n=21 Participants
Glycated Hemoglobin (HbA1c) Less Than (<) 8	11 participants n=5 Participants	14 participants n=7 Participants	12 participants n=5 Participants	12 participants n=4 Participants	49 participants n=21 Participants
Glycated Hemoglobin (HbA1c) Greater Than or Equal to (>=) 8	4 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	10 participants n=21 Participants
Duration of Diabetes	16.8 years n=5 Participants	23.9 years n=7 Participants	20.6 years n=5 Participants	16.7 years n=4 Participants	20.7 years n=21 Participants
Basal Insulin Daily Dose	0.309 units per kilogram (U/kg) STANDARD_DEVIATION 0.086 • n=5 Participants	0.283 units per kilogram (U/kg) STANDARD_DEVIATION 0.088 • n=7 Participants	0.341 units per kilogram (U/kg) STANDARD_DEVIATION 0.100 • n=5 Participants	0.267 units per kilogram (U/kg) STANDARD_DEVIATION 0.055 • n=4 Participants	0.301 units per kilogram (U/kg) STANDARD_DEVIATION 0.087 • n=21 Participants
Total Insulin Daily Dose	0.600 U/kg STANDARD_DEVIATION 0.237 • n=5 Participants	0.620 U/kg STANDARD_DEVIATION 0.179 • n=7 Participants	0.677 U/kg STANDARD_DEVIATION 0.204 • n=5 Participants	0.513 U/kg STANDARD_DEVIATION 0.115 • n=4 Participants	0.603 U/kg STANDARD_DEVIATION 0.193 • n=21 Participants

PRIMARY outcome

Timeframe: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)

Population: Continuous glucose monitoring (CGM) population: All participants who received at least 1 dose, had evaluable post-baseline CGM data, irrespective of compliance. Number of participants analyzed = participants with baseline, Weeks 7-8 (Period A) and/or Weeks 15-16 (Period B) CGM assessment. Missing data imputed using last observation carried forward.

Percentage of time with glucose within glycemic range (4.4-7.8 mmol/L) was assessed by the total time within glycemic range divided by the length of the assessment interval.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=30 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=27 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL])	31.75 percentage of time Standard Error 1.5	30.99 percentage of time Standard Error 1.58

SECONDARY outcome

Timeframe: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)

Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment. Missing data imputed using last observation carried forward (LOCF).

Percentage of time with glucose above the upper limit of glycemic range (\>7.8 mmol/L) was assessed by the total time above the upper limit of glycemic range divided by the length of the assessment interval.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=30 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=27 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Percentage of Time Above the Upper Limit of Glycemic Range (Greater Than [>] 7.8 mmol/L [(140 mg/dL])	58.24 percentage of time Standard Error 2.09	57.38 percentage of time Standard Error 2.2

SECONDARY outcome

Timeframe: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)

Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment. Missing data imputed using LOCF.

Percentage of time with glucose below the lower limit of glycemic range (\<4.4 mmol/L) was assessed by the total time below the lower limit of glycemic range divided by the length of the assessment interval.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=30 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=27 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Percentage of Time Below The Lower Limit of Glycemic Range (<4.4 mmol/L [80 mg/dL])	10.01 percentage of time Standard Error 1.02	11.64 percentage of time Standard Error 1.08

SECONDARY outcome

Timeframe: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)

Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment. Missing data imputed using LOCF.

The diurnal glucose exposure is measured as the average diurnal glucose concentration, diurnal glucose variability is measured by interquartile range (IQR), that is, average distance between the 25th and the 75th point-wise percentiles and diurnal glucose stability is assessed in terms of the mean absolute rate of change (mmol/l), that is, the area under the absolute rate of change of the median curve (based on the median point values between two adjacent hourly basket intervals), divided by the length of the assessment interval.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=30 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=27 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Evaluation of Diurnal Glucose Exposure, Variability, and Stability Diurnal Glucose Exposure	8.869 mmol/L Standard Error 0.24	8.910 mmol/L Standard Error 0.26
Evaluation of Diurnal Glucose Exposure, Variability, and Stability Diurnal Glucose Stability	0.673 mmol/L Standard Error 0.03	0.703 mmol/L Standard Error 0.03
Evaluation of Diurnal Glucose Exposure, Variability, and Stability Diurnal Glucose Variability	4.931 mmol/L Standard Error 0.22	5.279 mmol/L Standard Error 0.23

SECONDARY outcome

Timeframe: Weeks 7-8 in Period A and Weeks 15-16 in Period B

Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment, and n = participants with assessment at specified time-point.

Percentage of time with glucose within glycemic range (4.4-7.8 mmol/L) was assessed by the total time within glycemic range divided by the length of the assessment interval.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=29 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=27 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B Week 15, 16 (n=29, 26)	33.02 percentage of time Standard Deviation 13.48	28.70 percentage of time Standard Deviation 14.57
Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B Week 7, 8 (n=28, 27)	32.08 percentage of time Standard Deviation 14.74	29.07 percentage of time Standard Deviation 13.82

SECONDARY outcome

Timeframe: Baseline, Week 8, 16

Population: Modified Intent-to-Treat population: randomized participants who received at least 1 dose; had baseline, at least 1 post-baseline efficacy assessment; irrespective of compliance. Number of participants analyzed = participants with baseline, Week 8 and/or 16 HbA1c assessment, n = participants with HbA1c assessment at specified time. LOCF applied.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=29 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=27 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Change in HbA1c From Baseline to Week 8 and 16 Week 8 (n= 29, 20)	-0.22 percentage of hemoglobin Standard Deviation 0.48	-0.23 percentage of hemoglobin Standard Deviation 0.54
Change in HbA1c From Baseline to Week 8 and 16 Week 16 (n= 28, 27)	-0.44 percentage of hemoglobin Standard Deviation 0.51	-0.22 percentage of hemoglobin Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline, Week 8, 16

Population: Modified Intent-to-Treat population. Number of participants analyzed = participants with baseline, Week 8 and/or 16 FPG assessment, n = participants with FPG assessment at specified time. Missing data imputed using LOCF.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=24 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=23 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16 Week 8 (n=24, 23)	-0.89 mmol/L Standard Deviation 5.04	-0.10 mmol/L Standard Deviation 5.81
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16 Week 16 (n= 24, 22)	-0.99 mmol/L Standard Deviation 5.27	0.78 mmol/L Standard Deviation 4.92

SECONDARY outcome

Timeframe: Baseline, Week 8, 16

Population: Modified Intent-to-Treat population. Number of participants analyzed = participants with baseline, Week 8 and/or 16 7-point SMPG assessment, n = participants with 7-point SMPG assessment at specified time. Missing data imputed using LOCF.

Change in average of 7-point SMPG. 7-point SMPG was assessed starting with a measurement at before breakfast and 2 hours after breakfast; before and 2 hours after lunch; before and 2 hours after dinner; at bedtime.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=22 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=22 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16 Week 8	-0.39 mmol/L Standard Deviation 1.84	0.39 mmol/L Standard Deviation 1.54
Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16 Week 16	-0.47 mmol/L Standard Deviation 1.31	0.58 mmol/L Standard Deviation 2.13

SECONDARY outcome

Timeframe: Baseline, Week 8, 16

Population: Modified Intent-to-Treat population. Here n = participants with basal insulin dose assessment at specified time-point. Missing data imputed using LOCF.

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=30 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=29 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16 Week 8 (n= 30, 29)	0.06 U/kg Standard Deviation 0.09	0.03 U/kg Standard Deviation 0.09
Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16 Week 16 (n=29, 27)	0.05 U/kg Standard Deviation 0.09	0.03 U/kg Standard Deviation 0.08

SECONDARY outcome

Timeframe: Up to Week 16

Population: Safety population: all randomized participants who were exposed to at least one dose, regardless of amount of treatment administered. In the event of participants having received treatments different from those assigned according to the randomization schedule, safety analyses were conducted according to treatment received.

Hypoglycemia events were Severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); Documented symptomatic hypoglycemia (typical symptoms of hypoglycemia with plasma glucose level of \<=3.9 mmol/L \[70 mg/dL\]); Asymptomatic hypoglycemia (no typical symptoms of hypoglycemia but plasma glucose level \<=3.9 mmol/L); Probable symptomatic hypoglycemia (an event during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination, but was presumably caused by a plasma glucose level \<=3.9 mmol/L, symptoms treated with oral carbohydrate without a test of plasma glucose); Relative hypoglycemia (an event during which the person with diabetes reported any of the typical symptoms of hypoglycemia, and interpreted the symptoms as indicative of hypoglycemia, but plasma glucose level \>3.9 mmol/L); Severe and/or confirmed a hypoglycemia (plasma glucose \<=3.9 mmol/L).

Outcome measures

Outcome measures
Measure	HOE901-U300 Combined n=30 Participants HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=29 Participants Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Any Hypoglycemia Event: All Hypoglycemia	100 percentage of participants	100 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Severe Hypoglycemia: All Hypoglycemia	3.3 percentage of participants	10.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Documented Symptomatic: All Hypoglycemia	93.3 percentage of participants	96.6 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Asymptomatic: All Hypoglycemia	86.7 percentage of participants	96.6 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Probable Symptomatic: All Hypoglycemia	16.7 percentage of participants	27.6 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Relative: All Hypoglycemia	0.0 percentage of participants	6.9 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Severe and/or Confirmed: All Hypoglycemia	100 percentage of participants	100 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Any Hypoglycemia Event: Nocturnal Hypoglycemia	80.0 percentage of participants	93.1 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Severe Hypoglycemia: Nocturnal Hypoglycemia	0.0 percentage of participants	6.9 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Documented Symptomatic: Nocturnal Hypoglycemia	66.7 percentage of participants	79.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Asymptomatic: Nocturnal Hypoglycemia	40.0 percentage of participants	48.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Probable Symptomatic: Nocturnal Hypoglycemia	3.3 percentage of participants	10.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Relative: Nocturnal Hypoglycemia	0.0 percentage of participants	6.9 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 Severe and/or Confirmed: Nocturnal Hypoglycemia	80.0 percentage of participants	93.1 percentage of participants

Adverse Events

HOE901-U300 Combined

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Lantus Combined

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	HOE901-U300 Combined n=30 participants at risk HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=29 participants at risk Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
Gastrointestinal disorders Intestinal obstruction	3.3% 1/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	0.00% 0/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

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

Measure	HOE901-U300 Combined n=30 participants at risk HOE901-U300 SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.	Lantus Combined n=29 participants at risk Lantus SC injection once daily in morning or evening for 8 weeks during treatment period A, followed by once daily in evening or morning for 8 weeks during treatment period B.
General disorders Implant site bruising	10.0% 3/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	0.00% 0/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Infections and infestations Nasopharyngitis	30.0% 9/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	20.7% 6/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Infections and infestations Influenza	6.7% 2/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	10.3% 3/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Nervous system disorders Headache	6.7% 2/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	13.8% 4/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Nervous system disorders Migraine	6.7% 2/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	3.4% 1/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Respiratory, thoracic and mediastinal disorders Sinus congestion	6.7% 2/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	3.4% 1/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Respiratory, thoracic and mediastinal disorders Cough	3.3% 1/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	6.9% 2/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.3% 1/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	6.9% 2/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.3% 1/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	6.9% 2/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Gastrointestinal disorders Diarrhoea	10.0% 3/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	3.4% 1/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Gastrointestinal disorders Nausea	6.7% 2/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	3.4% 1/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Gastrointestinal disorders Vomiting	0.00% 0/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	10.3% 3/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
General disorders Pyrexia	10.0% 3/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	6.9% 2/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
General disorders Fatigue	6.7% 2/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	6.9% 2/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.
Investigations Weight increased	6.7% 2/30 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.	0.00% 0/29 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 16) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from first dose of study drug up to 2 days after the last dose of study drug). Analysis was done on safety population.