Trial Outcomes & Findings for Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes on Basal Insulin With Oral Antidiabetic Therapy (NCT NCT01499095)

NCT ID: NCT01499095

Last Updated: 2022-03-23

Results Overview

Only measurements performed before initiation of rescue therapy were considered in the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

811 participants

Primary outcome timeframe

Baseline, Month 6

Results posted on

2022-03-23

Participant Flow

A total of 1250 participants were screened, of whom 439 participants were screen failure and 811 participants were randomized.

Following the main 6 month treatment period, eligible participants previously using HOE901-U300 were randomized (1:1) in a substudy and continued with fixed-dosing (every 24 hours) or started a adaptable-dosing (at intervals of 24 +/- 3 hours) regimen for 3 Months (Month 6 to 9).

Participant milestones

Participant milestones
Measure	HOE901-U300 HOE901-U300 (new insulin glargine 300 units per milliliter \[U/mL\]) subcutaneous (SC) injection once daily (evening) for 12 months in combination with oral antidiabetic drug(s).	Lantus Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months in combination with oral antidiabetic drug(s).
Overall Study STARTED	404	407
Overall Study Treated	403	406
Overall Study Participated in Substudy	89	0
Overall Study Modified Intent-to-Treat Population	403	405
Overall Study COMPLETED	315	314
Overall Study NOT COMPLETED	89	93

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 (evening) for 12 months in combination with oral antidiabetic drug(s).	Lantus Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months in combination with oral antidiabetic drug(s).
Overall Study Randomized But Not Treated	1	1
Overall Study Adverse Event	12	7
Overall Study Lack of Efficacy	2	1
Overall Study Protocol Violation	6	7
Overall Study Received Rescue Therapy	32	40
Overall Study Diverse Reasons	22	25
Overall Study Lost to Follow-up	6	4
Overall Study Insulin Dropped Below Authorized Dose	0	5
Overall Study Hypoglycemia	3	1
Overall Study Diagnosed With Type 1 Diabetes Mellitus	2	1
Overall Study Change in Injection Schedule	2	0
Overall Study Perceived Lack of Efficacy	1	1

Baseline Characteristics

Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes on Basal Insulin With Oral Antidiabetic Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HOE901-U300 n=404 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=407 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Total n=811 Participants Total of all reporting groups
Age, Continuous	57.9 years STANDARD_DEVIATION 9.1 • n=5 Participants	58.5 years STANDARD_DEVIATION 9.2 • n=7 Participants	58.2 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	217 Participants n=5 Participants	222 Participants n=7 Participants	439 Participants n=5 Participants
Sex: Female, Male Male	187 Participants n=5 Participants	185 Participants n=7 Participants	372 Participants n=5 Participants
Body Mass Index (BMI)	34.8 kilogram per square meter STANDARD_DEVIATION 6.6 • n=5 Participants	34.8 kilogram per square meter STANDARD_DEVIATION 6.1 • n=7 Participants	34.8 kilogram per square meter STANDARD_DEVIATION 6.4 • n=5 Participants
Duration of Diabetes	11.6 years n=5 Participants	11.7 years n=7 Participants	11.7 years n=5 Participants
Basal Insulin Daily Dose	0.660 units per kilogram STANDARD_DEVIATION 0.221 • n=5 Participants	0.681 units per kilogram STANDARD_DEVIATION 0.253 • n=7 Participants	0.671 units per kilogram STANDARD_DEVIATION 0.238 • n=5 Participants
Glycated Hemoglobin A1c (HbA1c) Less Than (<) 8%	144 participants n=5 Participants	146 participants n=7 Participants	290 participants n=5 Participants
Glycated Hemoglobin A1c (HbA1c) Greater Than or Equal to (>=) 8%	260 participants n=5 Participants	261 participants n=7 Participants	521 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 6

Population: Modified Intent-to-Treat 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 Week 6 HbA1c assessment. Missing data imputed using last observation carried forward.

Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=386 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=392 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in HbA1c From Baseline to Month 6 Endpoint	-0.57 percentage of hemoglobin Standard Error 0.094	-0.56 percentage of hemoglobin Standard Error 0.093

SECONDARY outcome

Timeframe: Week 9 Up to Month 6

Population: Modified intent-to-treat population.

Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time), regardless the participant was awake or woke up because of the event. Severe hypoglycemia was an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Confirmed hypoglycemia was an event associated with plasma glucose less than or equal to (\<=) 3.9 mmol/L (70 milligram per deciliter \[mg/dL\]). Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=403 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=405 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint	21.6 percentage of participants	27.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT population. Missing data imputed using last observation carried forward. Number of participants analyzed = participants with baseline and Month 6 preinjection SMPG assessment.

Preinjection 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. Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=353 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=350 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint	-0.56 mmol/L Standard Error 0.278	-0.51 mmol/L Standard Error 0.275

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT population. Missing data imputed using last observation carried forward. Number of participants analyzed = participants with baseline and Month 6 preinjection SMPG assessment.

Preinjection SMPG was measured within 30 minutes prior to the injection of the study drug. Variability was assessed by the mean of co-efficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 3 SMPG measured during the 7 days preceding the assessment visit. Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=353 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=350 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint	-2.34 percentage of mean Standard Error 1.425	-0.53 percentage of mean Standard Error 1.408

SECONDARY outcome

Timeframe: Month 6

Population: mITT Population. Number of participants analyzed = participants with Month 6 HbA1c assessment. Missing data imputed using last observation carried forward.

Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=386 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=392 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Percentage of Participants With HbA1c <7% at Month 6 Endpoint	30.6 percentage of participants	30.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT Population. Number of participants analyzed = participants with baseline and Month 6 FPG assessment. Missing data imputed using last observation carried forward.

Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=375 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=379 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint	-1.03 mmol/L Standard Error 0.242	-1.21 mmol/L Standard Error 0.241

SECONDARY outcome

Timeframe: Month 6

Population: mITT Population. Number of participants analyzed = participants with Month 6 FPG assessment. Missing data imputed using last observation carried forward.

Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=384 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=390 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint	29.4 percentage of participants	33.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT population. Only participants from the mITT population with a value at baseline and at the specified timepoint were analyzed (represented by n=X, X in the category titles). Missing data imputed using last observation carried forward.

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. Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=403 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=405 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 03:00 at Night (n= 338, 328)	-0.56 mmol/L Standard Error 0.323	-0.90 mmol/L Standard Error 0.321
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Pre-breakfast (n= 347, 338)	-1.31 mmol/L Standard Error 0.221	-1.81 mmol/L Standard Error 0.219
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 2 hours after breakfast (n= 341, 328)	-1.41 mmol/L Standard Error 0.331	-1.82 mmol/L Standard Error 0.329
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Pre-lunch (n= 344, 332)	-0.64 mmol/L Standard Error 0.300	-1.12 mmol/L Standard Error 0.298
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 2 hours after lunch (n= 339, 328)	-1.02 mmol/L Standard Error 0.342	-1.04 mmol/L Standard Error 0.340
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Pre-dinner (n=347, 336)	-0.94 mmol/L Standard Error 0.327	-0.69 mmol/L Standard Error 0.324
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint 2 hours after dinner (n= 338, 327)	-0.69 mmol/L Standard Error 0.359	-1.00 mmol/L Standard Error 0.357
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint Bedtime (n= 325, 303)	-0.99 mmol/L Standard Error 0.345	-1.00 mmol/L Standard Error 0.343

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT Population. Number of participants analyzed = participants with Baseline and Month 6 basal insulin dose assessment. Missing data imputed using last observation carried forward.

Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=402 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=403 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint	0.28 U/kg Standard Error 0.021	0.17 U/kg Standard Error 0.021

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: mITT Population. Number of participants analyzed = participants with Baseline and Month 6 DTSQ assessment. Missing data imputed using last observation carried forward.

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. Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=346 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=359 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint	3.05 units on a scale Standard Error 0.448	3.61 units on a scale Standard Error 0.440

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=403 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=406 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Any Hypoglycemia Event: All Hypoglycemia	79.9 percentage of participants	83.0 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe Hypoglycemia: All Hypoglycemia	1.7 percentage of participants	1.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Documented Symptomatic: All Hypoglycemia	58.8 percentage of participants	63.3 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Asymptomatic: All Hypoglycemia	58.6 percentage of participants	64.0 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Probable Symptomatic: All Hypoglycemia	2.7 percentage of participants	3.4 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Relative: All Hypoglycemia	7.9 percentage of participants	12.8 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe and/or Confirmed: All Hypoglycemia	78.4 percentage of participants	82.0 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Any Hypoglycemia Event: Nocturnal Hypoglycemia	39.7 percentage of participants	46.1 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe Hypoglycemia: Nocturnal Hypoglycemia	0.2 percentage of participants	0.5 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Documented Symptomatic: Nocturnal Hypoglycemia	29.5 percentage of participants	34.2 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Asymptomatic: Nocturnal Hypoglycemia	14.4 percentage of participants	22.2 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Probable Symptomatic: Nocturnal Hypoglycemia	1.2 percentage of participants	1.0 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Relative: Nocturnal Hypoglycemia	2.2 percentage of participants	6.4 percentage of participants
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 Severe and/or Confirmed: Nocturnal Hypoglycemia	37.5 percentage of participants	44.6 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Month 6 up to Month 9

Population: mITT substudy population. Number of participants analyzed = participants with Month 6 and Month 9 HbA1c assessment. Analysis was planned to be performed for participants who were receiving HOE901-U300 (Adaptable dosing intervals or Fixed dosing intervals). Missing data imputed using last observation carried forward.

Substudy comparing fixed dosing regimen (every 24 hours) vs. adaptive dosing regimen (every 24 +/- 3 hours) in a subset of participants randomized to HOE901-U300 and treated for 6 months. Only measurements performed before initiation of rescue therapy were considered in the analysis.

Outcome measures

Outcome measures
Measure	HOE901-U300 n=40 Participants HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	Lantus n=37 Participants Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Change in HbA1c From Month 6 to Month 9	-0.12 percentage of hemoglobin Standard Error 0.151	-0.25 percentage of hemoglobin Standard Error 0.162

Adverse Events

HOE901-U300

Serious events: 30 serious events

Other events: 106 other events

Deaths: 0 deaths

LANTUS

Serious events: 30 serious events

Other events: 96 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	HOE901-U300 n=403 participants at risk HOE901-U300 SC injection once daily for 12 months in combination with oral antidiabetic drug(s).	LANTUS n=406 participants at risk Lantus SC injection once daily for 12 months in combination with oral antidiabetic drug(s).
Infections and infestations Bronchitis	6.2% 25/403 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). Analysis was done on safety population.	5.7% 23/406 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). Analysis was done on safety population.
Infections and infestations Nasopharyngitis	12.2% 49/403 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). Analysis was done on safety population.	7.6% 31/406 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). Analysis was done on safety population.
Infections and infestations Upper respiratory tract infection	5.7% 23/403 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). Analysis was done on safety population.	8.6% 35/406 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). Analysis was done on safety population.
Nervous system disorders Headache	6.7% 27/403 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). Analysis was done on safety population.	4.9% 20/406 • 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' (time from first injection of study drug up to 2 day after the last injection of study drug). 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