Effect of Soliqua 100/33 on Time in Range From Continuous Glucose Monitoring in Insulin-naive Patients With Very Uncontrolled Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

— Soli-CGM  

Official title:

A 16-week, Multicenter, Prospective, Open-label, Single-arm, Phase 4 Study to Evaluate the Effect of Soliqua™ 100/33 on the Percentage of Time in Range (TIR) From Continuous Glucose Monitoring (CGM) in Insulin-naïve Patients With Very Uncontrolled Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05114590
• Other study ID #: LPS16990
• Secondary ID: U1111-1261-7399
• Status: Completed
• Phase: Phase 4
• Start date: January 27, 2022
• Est. completion date: April 14, 2023

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study was to demonstrate if iGlarLixi (Soliqua 100/33) would improve glycemic control (as measured by Time in Range) and glycemic variability in participants with very uncontrolled (HbA1c ≥ 9%) type 2 Diabetes Mellitus (T2DM) while on at least 2 oral antidiabetic drugs [OADs] with or without a glucagon-like peptide 1 receptor agonist [GLP1 RA]), as measured by continuous glucose monitoring (CGM).

The total study duration per participant was approximately 22 weeks. Three site visits, 3 site or home visits, and up to 13 phone contacts were scheduled.

• A screening period of up to 2 weeks

• A run-in period of up to 2 weeks, including the baseline period

• A 16-week, open-label treatment period

• A 2-week post-treatment safety follow-up period

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: April 14, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with Type 2 Diabetes mellitus (T2DM) for at least 6 months before the baseline period

• HbA1c =9-13% during the run-in period

• On at least 2 OADs with or without GLP-1 RA with stable doses (for both) for 3 months prior to the screening period

• Willing and able to wear the CGM device continuously for 14 days to capture CGM measures at baseline until the next site visit and again towards the end of the treatment period

• Willing and able to prick fingers a minimum of 2-4 times per week utilizing sterile lancets provided along with a manual blood glucose meter kit

• Willing to discontinue the daily (oral or injectable) or weekly GLP-1 RA or DPP 4i prior to administration of iGlarLixi (Soliqua 100/33)

• Willing and able to inject iGlarLixi (Soliqua 100/33) and increase dose as needed to achieve SMPG target

• Non-pregnant, non-breastfeeding women utilizing a highly-effective contraceptive method or of non-childbearing potential

Exclusion Criteria:

• Type1 Diabetes mellitus (T1DM) or any other types of diabetes, except T2DM

• On meglitinides (eg, nateglinide, repaglinide)

• Body mass index (BMI) >40 kg/m² during the screening period

• Any current or previous skin conditions, including (but not limited to) severe psoriasis, burns, eczema, scarring, excessive tattoos, that would inhibit the proper wearing of the CGM device

• History of severe nausea and vomiting leading to subsequent discontinuation of GLP-1 RA

• Known history or presence of clinically significant pancreatitis or gastroparesis

• Participants with an episode of severe hypoglycemia or with hypoglycemia unawareness (defined as the onset of neuroglycopenia before the appearance of autonomic warning symptoms [for example, blurred vision, difficulty speaking, feeling faint, difficulty thinking, and confusion] or as the failure to sense a significant fall in blood glucose below normal levels) diagnosed within the 6 months prior to the screening period

• Participants with personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predisposed to MTC (eg, multiple endocrine neoplasia syndromes)

• Significant current (within past 2 months) and/or expected use of medications known to affect glycemia (eg, =5 mg/day prednisone)

• Use of substances known to interfere with CGM readings, such as aspirin-containing products (>650 mg/day of salicylic acid) or supplements containing vitamin C (>1000 mg/day of ascorbic acid) during the 14 days of CGM at either baseline or end of treatment period

• Previous treatment with any insulin (except for short term treatment due to intercurrent illness, including gestational diabetes, at the discretion of the investigator)

• Had used weight loss drugs (including over the counter and herbal medications) within 12 weeks before the screening visit

The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Insulin glargine/Lixisenatide
Solution for injection in a pre-filled pen by subcutaneous injection. Dose was individually titrated to achieve target fasting self-monitoring of plasma glucose (SMPG) of 80 to 100 milligrams per deciliter (mg/dL) (4.4 to 5.6 millimoles per liter [mmol/L]) while avoiding hypoglycemia.

Locations

Country	Name	City	State
United States	Hassman Research Institute - HRI - Berlin - CenExel - PPDS-Site Number:8400007	Berlin	New Jersey
United States	Clearview Medical Research LLC-Site Number:8400003	Canyon Country	California
United States	Endocrinology Associates Inc-Site Number:8400011	Columbus	Ohio
United States	University of Texas Southwestern Medical Center-Site Number:8400018	Dallas	Texas
United States	National Research Institute - ClinEdge - PPDS-Site Number:8400004	Huntington Park	California
United States	National Research Institute - ClinEdge - PPDS-Site Number:8400009	Huntington Park	California
United States	Palm Research Center, Inc.-Site Number:8400005	Las Vegas	Nevada
United States	Torrance Clinical Research Institute-Site Number:8400008	Lomita	California
United States	Downtown LA Research Center Inc - ClinEdge - PPDS-Site Number:8400001	Los Angeles	California
United States	University of Tennessee Health Science Center-Site Number:8400017	Memphis	Tennessee
United States	Floridian Research Institute-Site Number:8400013	Miami	Florida
United States	Premier Research Associate-Miami-Site Number:8400002	Miami	Florida
United States	Mid Hudson Medical Research PLLC-Site Number:8400014	New Windsor	New York
United States	Flourish Research - San Antonio - PPDS-Site Number:8400006	San Antonio	Texas
United States	Northeast Clinical Research of San Antonio LLC-Site Number:8400019	Schertz	Texas
United States	Consano Clinical Research LLC-Site Number:8400010	Shavano Park	Texas
United States	University Clinical Investigators Inc-Site Number:8400020	Tustin	California
United States	San Fernando Valley Health Institute - ClinEdge - PPDS-Site Number:8400012	West Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 16 in the Percentage of Time in Range [70 to 180 Milligram Per Deciliter (mg/dL)]	The percentage of time spent in the glycemic target range of 70 to 180 mg/dL was calculated as 100 times the number of recorded measurements in the glycemic target range (70 to 180 mg/dL inclusive), divided by the total number of recorded measurements. Baseline is defined as the first 14 evaluable days of evaluable continuous glucose monitoring (CGM) data prior to first day of treatment. CGM compliance is defined as 1) at least 8 out of 14 days (not necessarily consecutive) have 100% of evaluable CGM data per 24-hour period (at least 8 days with 96 records minimum per day) OR 2) at least 9 out of 14 days (not necessarily consecutive) have =89% of evaluable CGM data per 24-hour period (at least 9 days with 85 records minimum per day) OR 3) at least 10 out of 14 days (not necessarily consecutive) have at least =80% of evaluable CGM data per 24 hour period (at least 10 days with 77 records minimum per day).	Baseline (Days -14 to -1) and Week 16
Secondary	Percent Change From Baseline to Week 16 in Glucose Total Coefficient of Variation (CV)	Glucose total CV was calculated by following: standard deviation glucose/mean glucose over 14 days x 100, and the percent change was reported. Baseline is defined as the first 14 evaluable days of evaluable CGM data prior to first day of treatment.	Baseline (Days -14 to -1) and Week 16
Secondary	Change From Baseline to Week 16 in Mean Daily Blood Glucose	A global average was computed to determine the average of the mean daily blood glucose for the 14 days at baseline and Week 16. Baseline is defined as the first 14 evaluable days of evaluable CGM data prior to first day of treatment.	Baseline (Days -14 to -1) and Week 16
Secondary	Change From Baseline to Week 16 in the Maximum Postprandial Glucose Exposure in the 4 Hours Post-Breakfast Meal	The analysis was focused on the 4-hour interval at both baseline and Week 16 from t=0 (the timepoint at which glucose measurement was taken immediately preceding liquid meal administration) throughout the subsequent 4 hours. For each participant, the overall maximum glucose value within the described 4-hour period was determined, and the difference between the maximum glucose value at baseline and Week 16 was reported. Baseline is defined as the first 14 evaluable days of evaluable CGM data prior to first day of treatment.	Baseline (Days -14 to -1) and Week 16
Secondary	Change From Baseline to Week 16 in Time Above Range (>180 mg/dL)	The time spent above the glycemic target range was calculated as 100 times the total number of 15-minute increments of CGM data where a participant's blood glucose falls above normal range (>180 mg/dL) at baseline, divided by the total number of 15-minute increments read (i.e., up to 1344 15-minute increments) at Week 16. This was calculated for baseline and Week 16 and the change was reported. Baseline is defined as the first 14 evaluable days of evaluable CGM data prior to first day of treatment.	Baseline (Days -14 to -1) and Week 16
Secondary	Percentage of Participants Who Achieved Coefficient of Variation <36%	Percentage of participants achieving CV <36% was calculated as sum of the number of participants with CV <36% divided by the total number of participants. The endpoint was calculated using all CGM glucose readings available throughout each day for 2 weeks (Week 14-16).	Week 16
Secondary	Change From Baseline to Week 16 in Time in Range Per Time Blocks	Time spent in the glycemic target range (70 to 180 mg/dL) was calculated as 100 times the number of recorded measurements in the glycemic target range (70 to 180 mg/dL inclusive), divided by the total number of recorded measurements per time block and comparing the corresponding time blocks from Week 16 to baseline. The time blocks are 12 am to 6 am, 6 am to 12 pm, 12 pm to 6 pm, 6 pm to 12 am, and 6 am to 12 am. Baseline is defined as the first 14 evaluable days of evaluable CGM data prior to first day of treatment.	Baseline (Days -14 to -1) and Week 16
Secondary	Percentage of Participants Who Achieved Glucose Management Indicator (GMI) <7% and <9%	The GMI was calculated as 3.31 + 0.02392 x (mean glucose in mg/dL from CGM data). The GMI was calculated by determining the number of participants who achieved <7% and <9% at Week 16.	Week 16
Secondary	Change From Baseline to Week 16 in the 4-Hour Postprandial Glucose Area Under the Concentration Time Curve From 0 to 4 Hours	Blood samples were collected to measure the glucose values up to 4-hour after the breakfast meal. The analysis was based on a liquid meal at both baseline and Week 16 (a liquid meal administered in a fasted state and blood glucose is measured at specific time points up to 4 hours). Baseline is defined as the time period prior to administration of study drug.	Baseline (Days -14 to -1) and Week 16
Secondary	Change From Baseline to Week 16 in Time to Reach Maximum Postprandial Glucose Concentration	Blood samples were collected at specific intervals over a 4 hour period to measure blood glucose values following ingestion of a liquid meal and the process is repeated after 16 weeks of study drug administration following another liquid meal administration and blood glucose values measured at specific time points over 4 hours. The difference in the time to reach the maximal blood glucose value was then calculated between these two timepoints.	Baseline (Days -14 to -1) and Week 16
Secondary	Percentage of Participants Who Spent <15 Minutes/Day at a Glucose Level <54 mg/dL	Blood glucose level was determined based upon CGM data. Percentage of participants with glucose level <54 mg/dL for less than 15 minutes per day are reported.	Week 16
Secondary	Change From Baseline to Week 16 in Overall Score of Diabetes Medication Treatment Satisfaction Scores Using the Diabetes Medication Satisfaction Tool (DM-SAT) Questionnaire	The changes in diabetes medication treatment-related impact and satisfaction was measured by the DM-SAT. The DM-SAT is a 16-item measure with 4 domains/subscales assessing lifestyle (5 items), medical control (3 items), convenience (5 items) and well being (3 items). Each item is measured on a scale from 0-10, where 0= not at all satisfied, 1 to 3= not too satisfied, 4 to 6 = somewhat satisfied, 7-9= very satisfied and 10= extremely satisfied. The overall score was calculated as the sum of the 16 questions with a score that ranges from 0 to 160. A higher score indicates a positive result. Baseline is defined as the first 14 evaluable days of evaluable CGM data prior to first day of administration.	Baseline (Days -14 to -1) and Week 16
Secondary	Number of Participants With Confirmed Hypoglycemia Measured by Blood Glucose Levels	Hypoglycemia event is defined as any event recorded in hypoglycemic event information library electronic case report form page that has "Yes" as the response to the question "Were any hypoglycemic events experienced".; American Diabetes Association (ADA) Level 1 hypoglycemia is defined as measurable glucose concentration <70 mg/dL [3.9 millimoles per liter (mmol/L)] but >=54 mg/dL (3.0 mmol/L).; ADA Level 2 hypoglycemia is defined as measurable glucose concentration <54 mg/dL (3.0 mmol/L) that needed immediate action.; ADA Level 3 hypoglycemia is defined as severe event characterized by altered mental and/or physical functioning that required assistance from another person for recovery of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest.; Participants might have experienced both Level 1 and 2 hypoglycemia events.	From the first administration of the study drug (Day 1) up to 3 days after last administration of the study drug (maximum exposure duration: up to 16 weeks)
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events	An AE is any untoward medical occurrence in a participant or clinical study participant, whether or not considered related to the study drug. An SAE is defined as any AE that, at any dose, meets one of the following criteria: results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or congenital anomaly/birth defect. TEAEs is defined as AEs that developed, worsened, or became serious during the treatment-emergent period, defined as the time from the first administration of the study drug (Day 1) to the last administration of the study drug + 3 days.	From the first administration of the study drug (Day 1) up to 3 days after last administration of the study drug (maximum exposure duration: up to 16 weeks)