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

Phase 4

Terminated

Conditions: Type 2 Diabetes Mellitus
Renal Impairment

Interventions: Drug: Insulin degludec 100 U/mL
Drug: Insulin glargine 300 U/mL

Registration Number: NCT05552859

Lead Sponsor: Sanofi

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 62

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IDeg-100 arm	Insulin degludec 100 U/mL	Ideg-100 will be administered once daily for 24 weeks
Gla-300 arm	Insulin glargine 300 U/mL	Gla-300 will be administered once daily for 24 weeks

Primary Outcome Measures

Name	Time	Method
Difference in the Mean Change From Baseline to Week 24 in HbA1c Level (Gla-300 vs IDeg-100)	Baseline to 24 weeks	Change in HbA1c was calculated by subtracting baseline value from Week 24 value and then mean values were calculated.

Secondary Outcome Measures

Name	Time	Method
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24	Baseline to 24 weeks	Change in FPG was calculated by subtracting baseline value from the Week 24 value.
Change in Fasting Self-Measured Plasma Glucose (SMPG) From Baseline to Week 24	Baseline to 24 weeks	Change in SMPG was calculated by subtracting baseline value from the Week 24 value.
Change in 7-point SMPG Profiles From Baseline to Week 24, Per Time Point Within 24-hour Period	Baseline to 24 weeks	7-point SMPG profiles were measured at the following 7 points: pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.
Percentage of Participants Reaching HbA1c Target of <7.0% at Week 24	At week 24	If a patient has a missing HbA1c value at Week 24, it is assumed that they did not reach the HbA1c target of \<7.0%. HbA1c value of 7.0% is equivalent to 53.0 mmol/mol.
Percentage of Participants and Event Rate of Hypoglycemia by Trial Period (for ≤12 Weeks, for >13 Weeks to ≤24 Weeks)	Baseline to end of study (25 weeks)	Hypoglycemic events measured at the following intervals: Weeks 1-12 and Weeks 13-24.
Percentage of Participants With ≥1 Episode(s) of Confirmed Hypoglycemia Event (Cut-off Value 70 mg/dL and 54 mg/dL) During the 24-week Treatment Period.	Baseline to end of study (25 weeks)	Any event recorded with Yes as response to the question, "Was a glucose measurement obtained at the time of the event before countermeasure?" and a measurable glucose level of \<70 mg/dL. ADA (American Diabetes Association), Level 1 was defined as a measurable glucose concentration of \<70 mg/dL (3.9 mmol/L) but ≥54 mg/dL (3.0 mmol/L).
Rate of Hypoglycemia Per Participant-year	Baseline to end of study (25 weeks)]	Computed as: 365.25/12 × (number of episodes of hypoglycemia)/(number of days exposed in time window)
The 24-hour (All Time), Occurrence of Each Episode of Documented Hypoglycemia by Category, Presented by 2-hour Timeframe Over 24 Hours During the 24-week Treatment Period.	Baseline to end of study (25 weeks)	The time range for this outcome measure was 00:00 to 05:59, both inclusive. Hypoglycemia Categories \[(symptomatic, asymptomatic, severe) are defined per the American Diabetes Association/European Association for the Study of Diabetes hypoglycemia Classification\]
Number of Participants With Adverse Events (AEs)) and Serious Adverse Events (SAEs), Including Adverse Events of Special Interest (AESIs)	Baseline to end of study (25 weeks)	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.

Trial Locations

Locations (68): Yuma Clinical Trials, LLC Site Number: 8400028
🇺🇸
Yuma, Arizona, United States
American Clinical Trials Site Number: 8400014
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Buena Park, California, United States
Clearview Medical Research LLC Site Number: 8400021
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Canyon Country, California, United States
Torrance Clinical Research Institute Site Number: 8400003
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Lomita, California, United States
Center for Endocrinology Diabetes and Metabolic Disorders (CEDMD) - CAR Site Number: 8400026
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Santa Clarita, California, United States
San Fernando Valley Health Institute - ClinEdge - PPDS Site Number: 8400023
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Van Nuys, California, United States
Chase Medical Research LLC Site Number: 8400007
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Waterbury, Connecticut, United States
Innovative Research of West Florida Site Number: 8400016
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Clearwater, Florida, United States
Evolution Clinical Trials Site number: 8400034
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Hialeah Gardens, Florida, United States
Wellness Research Center Inc - Miami Site Number: 8400010
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Miami, Florida, United States
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Yuma Clinical Trials, LLC Site Number: 8400028
🇺🇸Yuma, Arizona, United States