Gla-300 and IDeg-100 in Insulin-Naïve People With Type 2 Diabetes Mellitus and Renal Impairment

Study Overview
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Brief Summary
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The TRENT trial is designed to confirm the efficacy and safety of Gla-300 compared with IDeg-100 in insulin-naïve patient (participants who have not tried insulin) with Type 2 Diabetes Mellitus (T2DM) and renal impairment. It will test the hypothesis that Gla-300 is non-inferior to IDeg-100 with glucose control. If achieved, the trial will also test for the superiority of Gla-300 compared with IDeg-100 in Hemoglobin A1c (HbA1c) reduction, without an increased potential risk of hypoglycemia.

Detailed Description
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The trial will consist of the following periods: A screening period of up to 2 weeks, A 24-week, open-label treatment period, including a titration period and a maintenance period. A 7-day, post-treatment, safety follow-up period after the last dose of the study drug or after premature/permanent discontinuation from study drug treatment. This will be a phone contact, but could be a site visit if ongoing or new AEs emerge during the post-treatment period, if necessary.

Official Title
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A 24-Week, Multicenter, Randomized, Open-Label, Parallel-Group Trial Comparing the Efficacy and Safety of Insulin Glargine 300 U/mL (Gla-300) and Insulin Degludec 100 U/mL (IDeg-100) in Insulin-Naïve People With Type 2 Diabetes Mellitus and Renal Impairment: TRENT Trial

Conditions
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Type 2 Diabetes Mellitus, Renal Impairment

Intervention / Treatment
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* Drug: Insulin glargine 300 U/mL
* Drug: Insulin degludec 100 U/mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is an adult aged ≥18 years at screening. Was diagnosed with Type 2 Diabetes Mellitus (T2DM) of >1-year duration and had glycemic levels above target with OADs (Oral Antidiabetic Drug) with or without GLP-1 RA (glucagon-like peptide-1 receptor agonist) (oral or injectable) at stable doses for ≥3 months before the screening period. Has an HbA1c ≥7.5% and ≤10.5% at screening. Has renal impairment, as defined by an eGFR (estimated glomerular filtration rate) of <60 mL/min/1.73m2 and ≥15 mL/min/1.73m2. Has adequately controlled blood pressure with stable antihypertensive therapy at trial inclusion. Is insulin-naïve, except for short use of insulin not exceeding 15 days during the last year before the screening period. Is capable of understanding the written informed consent, and provides signed written informed consent. Is willing and able to complete the electronic diary (eDiary) and agrees to comply with protocol requirements. Is willing and able to fast without having administered study drug for scheduled site visits. Exclusion Criteria: Has initiated treatment with potential novel therapies like dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA. Has a body mass index (BMI)* >45 kg/m² during the screening period. Has a history of hypoglycemia unawareness (defined as the onset of neuroglycopenia before the appearance of autonomic warning symptoms [eg, 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). Has a history of 2 or more episodes of severe hypoglycemia and/or 2 or more episodes of diabetic ketoacidosis within the 6 months before the day of screening. Has been exposed to other investigational drug(s) within 1 month or 5 half-lives from screening, whichever is longer. The above information is not intended to contain all considerations relevant to a participant's 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gla-300 arm<br>Gla-300 will be administered once daily for 24 weeks | Drug: Insulin glargine 300 U/mL<br>* Insulin glargine 300 U/mL in the SoloStar pen, self-administered once daily for 24 weeks.<br>* Other names: HOE901-U300;|
| Active Comparator: IDeg-100 arm<br>Ideg-100 will be administered once daily for 24 weeks | Drug: Insulin degludec 100 U/mL<br>* Insulin degludec 100 U/mL will be self- administered once daily for 24 weeks.<br>* Other names: Tresiba;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the mean change from baseline to Week 24 in HbA1c level (Gla-300 vs IDeg-100) |  | Baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) from baseline to Week 24 |  | Baseline to 24 weeks | 
| Change in fasting Self-Measured Plasma Glucose (SMPG) from baseline to Week 24 |  | Baseline to 24 weeks | 
| Change in 7-point SMPG profiles from baseline to Week 24, per time point within 24-hour period |  | Baseline to 24 weeks | 
| Percentage of participants reaching HbA1c target of <7.0% at Week 24 |  | At week 24 | 
| Percentage of participants with ≥1 episode(s) of confirmed hypoglycemia (cut-off value 70 mg/dL and 54 mg/dL) and event rate during the 24-week treatment period. |  | Baseline to end of study (25 weeks) | 
| Rate of hypoglycemia per participant-year computed as: 365.25/12 × (number of episodes of hypoglycemia)/(number of days exposed in time window). |  | Baseline to end of study (25 weeks) | 
| Percentage of participants and event rate of hypoglycemia by trial period (for ≤12 weeks, for >12 weeks to ≤24 weeks) |  | Baseline to end of study (25 weeks) | 
| The 24-hour (all time), daytime, and nocturnal (00:00 to 05:59, both inclusive) distribution of the occurrence of each episode of documented hypoglycemia by category, presented by 2-hour timeframe over 24 hours during the 24-week treatment period. | Hypoglycemia Categories [(symptomatic, asymptomatic, severe) are defined per the American Diabetes Association/European Association for the Study of Diabetes hypoglycemia Classification] | Baseline to end of study (25 weeks) | 
| Number of participants with adverse events (AEs)) and serious adverse events (SAEs), including adverse events of special interest (AESIs) | Adverse events (AEs) and serious adverse events (SAEs), including adverse events of special interest (AESIs), and other safety evaluations, including vital signs and body weight | Baseline to end of study (25 weeks) |