Trial Outcomes & Findings for Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 1 Diabetes Mellitus (NCT NCT01683266)

NCT ID: NCT01683266

Last Updated: 2015-06-24

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

549 participants

Primary outcome timeframe

Baseline, Month 6

Results posted on

2015-06-24

Participant Flow

A total of 846 participants were screened, of whom 297 participants were screen failure and 549 participants were randomized.

Participant milestones

Participant milestones
Measure	HOE901--U300 HOE901-U300 (new insulin glargine 300 units per milliliter \[U/mL\]) subcutaneous (SC) injection once daily in morning or evening for 12 months on top of mealtime insulin analogue.	Lantus Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily in morning or evening for 12 months on top of mealtime insulin analogue.
Overall Study STARTED	274	275
Overall Study Modified Intent-to-Treat Population	273	273
Overall Study COMPLETED	219	225
Overall Study NOT COMPLETED	55	50

Reasons for withdrawal

Reasons for withdrawal
Measure	HOE901--U300 HOE901-U300 (new insulin glargine 300 units per milliliter \[U/mL\]) subcutaneous (SC) injection once daily in morning or evening for 12 months on top of mealtime insulin analogue.	Lantus Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily in morning or evening for 12 months on top of mealtime insulin analogue.
Overall Study Adverse Event	5	4
Overall Study Lack of Efficacy	5	2
Overall Study Protocol Violation	13	6
Overall Study Personal Reason	17	25
Overall Study Selection Criterion / Protocol Violation	7	5
Overall Study Lost to Follow-up	5	0
Overall Study Site Closure / Site Withdrawal	1	3
Overall Study Nonserious Hypoglycemia	0	3
Overall Study Perceived Lack of Efficacy	1	1
Overall Study Possibly Hypoglycemia	1	0
Overall Study Serious Adverse Event of Hypoglycemia	0	1

Baseline Characteristics

Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 1 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HOE901--U300 n=274 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=275 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Total n=549 Participants Total of all reporting groups
Age, Continuous	46.4 years STANDARD_DEVIATION 13.9 • n=5 Participants	48.2 years STANDARD_DEVIATION 13.4 • n=7 Participants	47.3 years STANDARD_DEVIATION 13.7 • n=5 Participants
Sex: Female, Male Female	125 Participants n=5 Participants	111 Participants n=7 Participants	236 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants	164 Participants n=7 Participants	313 Participants n=5 Participants
Body Mass Index (BMI)	27.6 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.5 • n=5 Participants	27.6 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.7 • n=7 Participants	27.6 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.1 • n=5 Participants
Duration of Diabetes	20.5 years STANDARD_DEVIATION 12.7 • n=5 Participants	21.4 years STANDARD_DEVIATION 13.1 • n=7 Participants	21.0 years STANDARD_DEVIATION 12.9 • n=5 Participants
Glycated Hemoglobin (HbA1c) Less Than (<) 8%	105 participants n=5 Participants	105 participants n=7 Participants	210 participants n=5 Participants
Glycated Hemoglobin (HbA1c) Greater Than or Equal to (>=) 8%	169 participants n=5 Participants	170 participants n=7 Participants	339 participants n=5 Participants
Basal Insulin Daily Dose	0.381 units per kilogram (U/kg) STANDARD_DEVIATION 0.173 • n=5 Participants	0.372 units per kilogram (U/kg) STANDARD_DEVIATION 0.152 • n=7 Participants	0.376 units per kilogram (U/kg) STANDARD_DEVIATION 0.162 • n=5 Participants
Total Insulin Daily Dose	0.714 U/kg STANDARD_DEVIATION 0.278 • n=5 Participants	0.724 U/kg STANDARD_DEVIATION 0.245 • n=7 Participants	0.719 U/kg STANDARD_DEVIATION 0.262 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 6

Population: Modified Intent-to-Treat (mITT) population: all randomized participants who received at least (\>=)1 dose, had baseline and \>=1 post-baseline assessment of any efficacy variable, irrespective of compliance. Number of participants analyzed = participants with baseline and Month 6 HbA1c assessment.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=225 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=229 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Change In HbA1c From Baseline to Month 6 Endpoint	-0.40 percentage of hemoglobin Standard Error 0.051	-0.44 percentage of hemoglobin Standard Error 0.051

SECONDARY outcome

Timeframe: Month 6

Population: mITT Population.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=273 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=273 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Percentage of Participants With HbA1c <7% at Month 6 Endpoint	16.8 percentage of participants	15.0 percentage of participants

SECONDARY outcome

Timeframe: Month 6

Population: mITT Population.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=273 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=273 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Percentage of Participants With HbA1c Less Than or Equal to 6.5% at Month 6 Endpoint	8.1 percentage of participants	5.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT population. Number of participants analyzed = participants with baseline and Month 6 pre-injection SMPG assessment.

Pre-injection SMPG was measured within 30 minutes prior to the injection of the study drug. Average was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=117 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=105 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Change In Average Pre-Injection Self-Monitored Plasma Glucose (SMPG) From Baseline Month 6 Endpoint	-1.16 millimole per liter (mmol/L) Standard Error 0.223	-0.82 millimole per liter (mmol/L) Standard Error 0.233

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT population. Number of participants analyzed = participants with baseline and Month 6 pre-injection SMPG assessment.

Pre-injection SMPG was measured within 30 minutes prior to the injection of the study drug. Variability was assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 3 SMPG measured during the 7 days preceding the assessment visit.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=117 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=105 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Change in Variability of Pre-injection SMPG From Baseline to Month 6 Endpoint	-3.03 percentage of mean Standard Error 1.573	-1.76 percentage of mean Standard Error 1.651

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT Population. Number of participants analyzed = participants with baseline and Month 6 FPG assessment.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=213 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=216 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Change in Fasting Plasma Glucose From Baseline to Month 6 Endpoint	-0.95 mmol/L Standard Error 0.263	-1.14 mmol/L Standard Error 0.260

SECONDARY outcome

Timeframe: Month 6

Population: mITT Population.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=273 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=273 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Percentage of Participants With Fasting Plasma Glucose (FPG) <5.6 mmol/L (100 mg/dL) At Month 6	9.9 percentage of participants	12.8 percentage of participants

SECONDARY outcome

Timeframe: Month 6

Population: mITT Population. Number of participants analyzed = participants with baseline and Month 6 FPG assessment.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=273 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=273 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Percentage of Participants With FPG <7.2 mmol/L (130 mg/dL) at Month 6 Endpoint	25.3 percentage of participants	25.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT Population. Here, n = participants with Baseline and Month 6 8-point SMPG assessment separately for each analysed time point.

Change in each time-point of 8-point SMPG profile: 03:00 hours (clock time) at night; before and 2 hours after breakfast; before and 2 hours after lunch; before and 2 hours after dinner; and at bedtime.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=273 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=273 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 03:00 at Night (n= 156, 159)	-0.47 mmol/L Standard Deviation 4.56	-0.67 mmol/L Standard Deviation 4.98
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Pre--Breakfast (n= 166, 167)	-0.86 mmol/L Standard Deviation 5.30	-0.07 mmol/L Standard Deviation 5.20
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 2 Hours After Breakfast (n= 152, 156)	-0.62 mmol/L Standard Deviation 4.75	-1.18 mmol/L Standard Deviation 5.66
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Pre--Lunch (n= 166, 166)	-0.95 mmol/L Standard Deviation 4.53	-0.93 mmol/L Standard Deviation 4.76
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 2 Hours After Lunch (n= 163,163)	-0.13 mmol/L Standard Deviation 5.20	-1.43 mmol/L Standard Deviation 5.37
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Pre--Dinner (n= 165,166)	-0.56 mmol/L Standard Deviation 6.00	-1.74 mmol/L Standard Deviation 5.28
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 2 Hours After Dinner (n= 154,152)	-0.93 mmol/L Standard Deviation 5.27	-1.19 mmol/L Standard Deviation 5.51
Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Bedtime (n= 141,146)	-0.80 mmol/L Standard Deviation 5.39	-1.91 mmol/L Standard Deviation 5.10

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT Population. Number of participants analyzed = participants with Baseline and Month 6 daily average total insulin dose assessment.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=173 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=158 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Change in Daily Average Total Insulin Dose From Baseline to Month 6 Endpoint	0.19 U/kg Standard Deviation 0.22	0.10 U/kg Standard Deviation 0.16

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT Population. Number of participants analyzed = participants with Baseline and Month 6 DTSQ assessment.

DTSQ is a validated measure to assess how satisfied participants with diabetes are with their treatment and how they perceive hyper- and hypoglycemia. It consists of 8 questions which are answered on a Likert scale from 0 to 6. DTSQ treatment satisfaction score is the sum of question 1 and 4-8 scores and ranges between 0 and 36, where higher scores indicate more treatment satisfaction.

Outcome measures

Outcome measures
Measure	HOE901--U300 n=212 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=206 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Change in Total Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint	1.00 units on a scale Standard Error 0.331	1.41 units on a scale Standard Error 0.334

SECONDARY outcome

Timeframe: Up to Month 12

Population: Safety population: all participants randomized and exposed to at least one dose of study drug, regardless of the 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 n=274 Participants HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=275 Participants Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Any Hypoglycemia Event: All Hypoglycemia	95.3 percentage of participants	94.9 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe Hypoglycemia: All Hypoglycemia	9.1 percentage of participants	11.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Documented Symptomatic: All Hypoglycemia	87.6 percentage of participants	86.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Asymptomatic: All Hypoglycemia	76.6 percentage of participants	81.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Probable Symptomatic: All Hypoglycemia	11.3 percentage of participants	15.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Relative: All Hypoglycemia	14.6 percentage of participants	9.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe and/or Confirmed: All Hypoglycemia	94.9 percentage of participants	94.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Any Hypoglycemia Event: Nocturnal Hypoglycemia	73.4 percentage of participants	74.9 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe Hypoglycemia: Nocturnal Hypoglycemia	3.3 percentage of participants	3.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Documented Symptomatic: Nocturnal Hypoglycemia	64.2 percentage of participants	63.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Asymptomatic: Nocturnal Hypoglycemia	35.0 percentage of participants	38.9 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Probable Symptomatic: Nocturnal Hypoglycemia	5.1 percentage of participants	6.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Relative: Nocturnal Hypoglycemia	4.0 percentage of participants	5.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe and/or Confirmed: Nocturnal Hypoglycemia	72.6 percentage of participants	74.5 percentage of participants

Adverse Events

HOE901--U300

Serious events: 27 serious events

Other events: 113 other events

Deaths: 0 deaths

Lantus

Serious events: 26 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	HOE901--U300 n=274 participants at risk HOE901-U300 SC injection once daily in morning or evening for 12 months on top of mealtime insulin.	Lantus n=275 participants at risk Lantus SC injection once daily in morning or evening for 12 months on top of mealtime insulin.
Infections and infestations Influenza	5.8% 16/274 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.	5.1% 14/275 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.
Infections and infestations Nasopharyngitis	15.7% 43/274 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.	12.7% 35/275 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.
Infections and infestations Sinusitis	5.1% 14/274 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.	4.0% 11/275 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.
Infections and infestations Upper respiratory tract infection	13.9% 38/274 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.	9.5% 26/275 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.
Musculoskeletal and connective tissue disorders Back pain	5.1% 14/274 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.	2.5% 7/275 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.
Nervous system disorders Headache	6.2% 17/274 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.	4.7% 13/275 • All Adverse Events (AE) were collected from signature of informed consent form up to study completion regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (as the time from first injection of IMP up to 2 days after the last injection of IMP). Analysis was done on safety population.

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