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

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate if Soliqua 100/33 improves 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 glucagonlike peptide 1 receptor agonist [GLP1 RA]), as measured by continuous glucose monitoring (CGM). The total study duration per participant will be approximately 22 weeks. Three site visits, 3 site or home visits, and up to 13 phone contacts are scheduled. A screening period of up to 2 weeks A run-in period of up to 2 weeks and includes the baseline period A 16-week, open-label treatment period A 2-week post-treatment safety follow-up period

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glargine/Lixisenatide


Participation Criteria
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Eligibility Criteria
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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 Soliqua 100/33 Willing and able to inject Soliqua 100/33 and increase dose as needed to achieve SMPG target Non-pregnant, non-breastfeeding women utilizing a high-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 predisposes 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) Has used weight loss drugs (including over the counter and herbal medications) within 12 weeks before the screening visit The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Soliqua 100/33<br>Soliqua 100/33 (Insulin glargine 100 Units/ml /lixisenatide 33 μg/mL) once daily for 16 weeks. | Drug: Insulin glargine/Lixisenatide<br>* Solution for injection in a pre-filled pen by subcutaneous injection<br>* Other names: AVE0010-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to week 16 in the percentage of Time in Range (TIR) | TIR defined as 70-180 mg/dL | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 16 in coefficient of variation (CV) |  | Baseline, Week 16 | 
| Change from baseline to Week 16 in mean daily blood glucose |  | Baseline, Week 16 | 
| Change from baseline to Week 16 in the maximum Post Prandial Glucose exposure in the 4 hours post-breakfast meal |  | Baseline, Week 16 | 
| Change from baseline to Week 16 in Time above range (TAR) | TAR defined as > 180mg/dL | Baseline, Week 16 | 
| Percentage of participants achieving CV <36% |  | Week 16 | 
| Change from baseline to Week 16 in TIR per time blocks | TIR (70-180 mg/dL) for specific time blocks defined as 6 am-12 pm; 12 pm-6 pm; 6 pm-12 am, and 12 am-6 am | Baseline, Week 16 | 
| Percentage of participants achieving Glucose Management Indicator (GMI) | GMI < 7% and < 9% | Week 16 | 
| Change from baseline to Week 16 in the 4-hour PPG area under the concentration time curve (AUC0-4h) | After start of the breakfast meal | Baseline, Week 16 | 
| Change from baseline to Week 16 in Time to reach maximum PPG concentration (Tmax) | After start of the breakfast meal | Baseline, Week 16 | 
| Percentage of participants who spend <15 minutes/day at a glucose level <54 mg/dL |  | Week 16 | 
| Change from baseline to Week 16 in diabetes medication treatment satisfaction scores | The Diabetes Medication Satisfaction Tool (DM SAT) questionnaire is a 16-item measure with higher score indicative of better satisfaction | Baseline, Week 16 | 
| Number of participants with confirmed hypoglycemia | Including overall hypoglycemia, hypoglycemia with glucose concentration <70 mg/dL (3.9 mmol/L) but ≥54 mg/dL (3.0 mmol/L), <54 mg/dL (3.0 mmol/L) and severe hypoglycemia | Baseline up to end of study (Week 18) | 
| Number of participants with adverse events |  | Baseline up to end of study (Week 18) |