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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Active-controlled, Parallel Group, 16-Week Open Label Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo (Insulin Glargine-U300) Versus Lantus in Patients With Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02688933
• Other study ID #: LPS14587
• Secondary ID: U1111-1176-0936
• Status: Completed
• Phase: Phase 4
• Start date: May 5, 2016
• Est. completion date: June 19, 2017

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate that morning injection of Toujeo (HOE901-U300) compared to Lantus provides better glycemic control evaluated by Continuous Glucose Monitoring (CGM) in adult participants with type 1 diabetes mellitus.

Secondary Objective:

To demonstrate that treatment with HOE901-U300 compared to Lantus provides:

• Lower incidence rate of nocturnal symptomatic hypoglycemia;

• Better glucose control coverage during the last hours of CGM before next basal-insulin dosing;

• Less variability in CGM profile.

Description:

The maximum study duration per participant was to be of approximately 20 weeks that consisted of an up to a 4-week screening and CGM training period including a 1-2 week baseline (blinded) CGM performance (allowed for re-training), a 14-week open-label, comparative treatment period allowing for dose titration in both basal and meal-time insulin and including a 1-2 week end-of treatment blinded CGM collection with fixed dose of HOE901-U300 and Lantus, and a 2 day post treatment follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 638
• Est. completion date: June 19, 2017
• Est. primary completion date: June 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria:

• Adult participants (male and female) with type 1 diabetes mellitus (T1DM).

• Signed written informed consent.

Exclusion criteria:

• Age <18 years or >70 years.

• Fasting c-peptide =0.3 nmol/L as per source document or central lab test at Visit 1.

• Glycated hemoglobin (HbA1c) = 6.5 % or = 10.0% via central lab test at Visit 1.

• Participants who experienced none of episode of documented symptomatic and/or severe hypoglycemia (as per the American Diabetes Association (ADA) classification) during the past month prior to screening.

• Participants who experienced >1 episode of severe hypoglycemia resulting in coma/seizures during the last 12 months before screening.

• Participants received less than 1 year treatment with basal plus mealtime insulin.

• Used any basal insulins other than long-acting insulin analogs (ie, Lantus, Toujeo, Levemir, and Tresiba) in the past 3 months before screening.

• Required >80 U/day basal insulin analogs or not on stable dose (±20% total dose) within 30 days prior to screening.

• Used fewer than 2 injections of rapid-acting insulin analog per day within 30 days prior to screening.

• Used human regular insulin as mealtime insulin within 30 days prior to screening.

• Used an insulin pump during the last 6 months before screening.

• History of unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to required treatment (e.g., laser, surgical treatment, or injectable drugs) during the study period.

• Pregnant or breast-feeding women or planned pregnancy during the duration of the study.

• Use of any other investigational drug(s) within 1 month or 5 half-lives, whichever was longer prior to screening.

• Inappropriate CGM use during screening period evidenced by failure to obtain a minimum of 4 days of usable records by the end of screening.

• Noncompliance with self-monitored plasma glucose (SMPG) performance evidenced by failure to demonstrate at least 5 days of 5 point SMPG records by the end of screening.

The above information is not intended to contain all considerations relevant to a participants's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• HOE901-U300 (Insulin Glargine 300 U/ml)
Self-administered by subcutaneous (SC) injection in the morning (between waking up and breakfast) using a pre-filled pen.
• Lantus (Insulin Glargine 100 U/ml)
Self-administered by subcutaneous (SC) injection in the morning (between waking up and breakfast using a pre-filled pen.
• Mandated back ground therapy
Rapid insulin analogs: e.g., insulin glulisine, insulin lispro or insulin aspart, used by participant at least 30 days before screening. Mealtime insulin was to be continued during the study and titrated towards protocol specified postprandial glucose targets (130-180 mg/dL).

Locations

Country	Name	City	State
Puerto Rico	Investigational Site Number 840-111	Manati
United States	Investigational Site Number 840-125	Arlington Heights	Illinois
United States	Investigational Site Number 840-001	Atlanta	Georgia
United States	Investigational Site Number 840-162	Bend	Oregon
United States	Investigational Site Number 840-143	Bennington	Vermont
United States	Investigational Site Number 840-067	Billings	Montana
United States	Investigational Site Number 840-139	Bridgeport	West Virginia
United States	Investigational Site Number 840-056	Burlington	Vermont
United States	Investigational Site Number 840-058	Chattanooga	Tennessee
United States	Investigational Site Number 840-011	Chicago	Illinois
United States	Investigational Site Number 840-064	Columbus	Georgia
United States	Investigational Site Number 840-123	Columbus	Ohio
United States	Investigational Site Number 840-071	Concord	California
United States	Investigational Site Number 840-072	Coral Gables	Florida
United States	Investigational Site Number 840-062	Covington	Kentucky
United States	Investigational Site Number 840-134	Crystal Lake	Illinois
United States	Investigational Site Number 840-003	Dallas	Texas
United States	Investigational Site Number 840-005	Dallas	Texas
United States	Investigational Site Number 840-013	Dallas	Texas
United States	Investigational Site Number 840-019	Dallas	Texas
United States	Investigational Site Number 840-075	Dallas	Texas
United States	Investigational Site Number 840-021	Denver	Colorado
United States	Investigational Site Number 840-039	Denver	Colorado
United States	Investigational Site Number 840-070	Denver	Colorado
United States	Investigational Site Number 840-153	El Paso	Texas
United States	Investigational Site Number 840-046	Englewood	Colorado
United States	Investigational Site Number 840-149	Escondido	California
United States	Investigational Site Number 840-051	Fargo	North Dakota
United States	Investigational Site Number 840-037	Flint	Michigan
United States	Investigational Site Number 840-026	Fort Worth	Texas
United States	Investigational Site Number 840-157	Framingham	Massachusetts
United States	Investigational Site Number 840-004	Fresno	California
United States	Investigational Site Number 840-110	Greenbrae	California
United States	Investigational Site Number 840-045	Greenville	North Carolina
United States	Investigational Site Number 840-040	Henderson	Nevada
United States	Investigational Site Number 840-133	Hialeah	Florida
United States	Investigational Site Number 840-031	Houston	Texas
United States	Investigational Site Number 840-081	Houston	Texas
United States	Investigational Site Number 840-152	Houston	Texas
United States	Investigational Site Number 840-156	Houston	Texas
United States	Investigational Site Number 840-160	Houston	Texas
United States	Investigational Site Number 840-054	Hyattsville	Maryland
United States	Investigational Site Number 840-060	Idaho Falls	Idaho
United States	Investigational Site Number 840-124	La Jolla	California
United States	Investigational Site Number 840-030	La Mesa	California
United States	Investigational Site Number 840-017	Las Vegas	Nevada
United States	Investigational Site Number 840-012	Lawrenceville	Georgia
United States	Investigational Site Number 840-042	Lexington	Kentucky
United States	Investigational Site Number 840-094	Lincoln	Nebraska
United States	Investigational Site Number 840-151	Little Rock	Arkansas
United States	Investigational Site Number 840-022	Los Angeles	California
United States	Investigational Site Number 840-044	Los Angeles	California
United States	Investigational Site Number 840-129	Los Gatos	California
United States	Investigational Site Number 840-140	Lufkin	Texas
United States	Investigational Site Number 840-137	Maitland	Florida
United States	Investigational Site Number 840-104	Mentor	Ohio
United States	Investigational Site Number 840-029	Mesquite	Texas
United States	Investigational Site Number 840-009	Metairie	Louisiana
United States	Investigational Site Number 840-049	Miami	Florida
United States	Investigational Site Number 840-076	Miami	Florida
United States	Investigational Site Number 840-010	Morehead City	North Carolina
United States	Investigational Site Number 840-080	Morehead City	North Carolina
United States	Investigational Site Number 840-083	Murray	Utah
United States	Investigational Site Number 840-032	New Orleans	Louisiana
United States	Investigational Site Number 840-023	New Port Richey	Florida
United States	Investigational Site Number 840-102	New York	New York
United States	Investigational Site Number 840-108	New York	New York
United States	Investigational Site Number 840-079	Norman	Oklahoma
United States	Investigational Site Number 840-048	North Richland Hills	Texas
United States	Investigational Site Number 840-024	Northridge	California
United States	Investigational Site Number 840-053	Ocoee	Florida
United States	Investigational Site Number 840-101	Ogden	Utah
United States	Investigational Site Number 840-033	Omaha	Nebraska
United States	Investigational Site Number 840-142	Omaha	Nebraska
United States	Investigational Site Number 840-112	Ormond Beach	Florida
United States	Investigational Site Number 840-018	Palm Harbor	Florida
United States	Investigational Site Number 840-150	Pearland	Texas
United States	Investigational Site Number 840-069	Pomona	California
United States	Investigational Site Number 840-090	Pomona	California
United States	Investigational Site Number 840-047	Port Charlotte	Florida
United States	Investigational Site Number 840-096	Portland	Oregon
United States	Investigational Site Number 840-015	Renton	Washington
United States	Investigational Site Number 840-006	Rockville	Maryland
United States	Investigational Site Number 840-132	Rolling Hills Estates	California
United States	Investigational Site Number 840-008	Roswell	Georgia
United States	Investigational Site Number 840-097	Salt Lake City	Utah
United States	Investigational Site Number 840-130	San Jose	California
United States	Investigational Site Number 840-055	San Ramon	California
United States	Investigational Site Number 840-028	Santa Barbara	California
United States	Investigational Site Number 840-074	Spokane	Washington
United States	Investigational Site Number 840-109	Staten Island	New York
United States	Investigational Site Number 840-014	Stockbridge	Georgia
United States	Investigational Site Number 840-114	Tampa	Florida
United States	Investigational Site Number 840-063	Tarzana	California
United States	Investigational Site Number 840-138	Tustin	California
United States	Investigational Site Number 840-016	Ventura	California
United States	Investigational Site Number 840-122	Waltham	Massachusetts
United States	Investigational Site Number 840-002	West Des Moines	Iowa
United States	Investigational Site Number 840-036	West Palm Beach	Florida
United States	Investigational Site Number 840-073	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Daily Insulin Dose at Week 16	Change from Baseline at Week 16 for daily basal insulin dose and daily bolus insulin dose was reported.	Baseline, Week 16
Primary	Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM	The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained from a generalized linear model with identity link including post baseline CGM assessment during Week 15 (and/or Week 16).	During Week 15 and/or 16
Secondary	Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia	Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia electronic case report form (eCRF).	Baseline up to Week 16
Secondary	Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year	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 eCRF.	Baseline up to Week 16
Secondary	Mean Change From Baseline in Glucose Level During Last 4 Hours of CGM Data Collection Prior to the Next Day Basal Insulin Injection During Week 15 and/or Week 16	Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16).	Baseline, during Week 15 and/or Week 16
Secondary	Percentage of Time Glucose Concentrations Within the Target Range of 70 to 140 mg/dL During Last 4 Hours of CGM Data Collection Prior to Next Day Basal Insulin Injection	Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16).	During Week 15 and/or Week 16
Secondary	Coefficient of Variation (CV%) in Mean CGM Glucose	CV% was a measure of spread of variability relative to mean of population. For CGM glucose values over 24 hours, CV% was measure of glycemic variability across 24-hour day and calculated for each period (total, within day and between days) as ratio of standard deviation of glucose values to mean of glucose values.	During Week 15 and/or Week 16