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

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

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus; Renal Impairment
• Intervention / Treatment: Drug: Insulin glargine 300 U/mL; Drug: Insulin degludec 100 U/mL

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sanofi Trial Transparency Email Recommended (Toll free for US and Canada); Phone Number: Opt. 6 800-633-1610; Email: contact-us@sanofi.com
• Study Contact Backup: Name: Clinical Sciences & Operations Study Director

Study Locations

• Czechia
  • Brandýs Nad Labem-Stará Boleslav, Czechia, 250 01
    • Diacentrum Brandys n. L. Site Number: 2030004
  • Jílové U Prahy, Czechia, 254 00
    • Diabetologicka, interni a obezitologicka ambulance Site Number: 2030005
  • Praha, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady Site Number: 2030007
  • Moravskoslezský Kraj
    • Krnov, Moravskoslezský Kraj, Czechia, 794 01
      • Diabetologie MUDr. Tomas Edelsberger Site Number: 2030001
  • Olomoucký Kraj
    • Olomouc, Olomoucký Kraj, Czechia, 779 00
      • Agentura Science Pro spol. s.r.o.Site Number: 2030002
  • Praha, Hlavní Mesto
    • Prague, Praha, Hlavní Mesto, Czechia, 140 21
      • Institut Klinicke A Experimentalni Mediciny Site Number: 2030006
• Hungary
  • Budapest, Hungary, 1134
    • Magyar Honvédség Egészségügyi Központ Site Number: 3480003
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mór Oktató Kórház Site Number: 3480004
  • Szabolcs-Szatmár-Bereg
    • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
      • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Site Number: 3480006
  • Vas
    • Szombathely, Vas, Hungary, 9700
      • Markusovszky Egyetemi Oktatókórház Site Number: 3480001
  • Veszprém
    • Balatonfüred, Veszprém, Hungary, 8230
      • Csolnoky Ferenc Korhaz Site Number: 3480005
  • Zala
    • Zalaegerszeg, Zala, Hungary, 8904
      • Zala Megyei Szent Rafael Korhaz Site Number: 3480002
• Poland
  • Lódz, Poland, 90-132
    • Gabinet Lekarski Malgorzata Saryusz-Wolska Site Number: 6160017
  • Poznan, Poland, 61-655
    • Praktyka Lekarska Ewa Krzyzagórska Site Number: 6160014
  • Radom, Poland, 26-600
    • Prywatny Gabinet Lekarski, Centrum Medyczne "Diabetika" Site Number:6160002
  • Skierniewice, Poland, Lódzkie
    • ETG Skierniewice - PPDS Site Number: 6160006
  • Łódź, Poland, 90-302
    • ETG Lodz Site Number: 6160018
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-127
      • Regionalna Poradnia Diabetologiczna - Wroclaw Site Number: 6160009
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-538
      • Niepubliczny Zaklad Opieki Zdrowotnej Przychodnia Specjalistyczna Medica Site Number: 6160008
    • Puławy, Lubelskie, Poland, 24-100
      • KO-MED Centra Kliniczne Sp. z o.o. Site Number: 6160010
    • Zamość, Lubelskie, Poland, 22-400
      • KO-MED Centra Kliniczne Sp. z o.o. Site Number: 6160012
  • Malopolskie
    • Kraków, Malopolskie, Poland, 31-548
      • Zaklad Opieki Medycznej "Sanatio" Sp.z o.o. - Osrodek Leczenia Schorzen Cywilizacyjnych Site Number: 6160016
  • Mazowieckie
    • Radom, Mazowieckie, Poland, 26-610
      • Prywatny Gabinet Lekarski Centrum Medyczne Diabetika Dorota Mlodawska-Choluj Site Number: 6160015
    • Warszawa, Mazowieckie, Poland, 00-465
      • NBR Polska Site Number: 6160003
    • Warszawa, Mazowieckie, Poland, 02-507
      • Centralny Szpital Kliniczny MSW Site Number: 6160005
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-858
      • NZOZ Gdanska Poradnia Cukrzycowa Sp. z o.o. Site Number: 6160014
  • Slaskie
    • Częstochowa, Slaskie, Poland, 42-207
      • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Site Number: 6160001
    • Lubliniec, Slaskie, Poland, 42-700
      • Specjalistyczna Praktyka Lekarska Site Number: 6160004
  • Swietokrzyskie
    • Staszów, Swietokrzyskie, Poland, 28-200
      • KO-MED Centra Kliniczne Sp. z o.o. Site Number:6160011
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-111
      • Centrum Medyczne OMEDICA Site Number: 6160013
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Centar Zvezdara Site Number: 6880001
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia - PPDS Site Number: 6880003
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia - PPDS Site Number: 6880004
  • Niš, Serbia, 18 000
    • University Clinical Center Nis Site Number: 6880002
  • Niš, Serbia, 18 000
    • University Clinical Center Nis Site Number: 6880005
  • Zaječar, Serbia, 19000
    • Health Center Zajecar Site Number: 6880006
• United States
  • Arizona
    • Yuma, Arizona, United States, 85364-7110
      • Yuma Clinical Trials, LLC Site Number: 8400028
  • California
    • Buena Park, California, United States, 90620-3800
      • American Clinical Trials Site Number: 8400014
    • Canyon Country, California, United States, 91351-4138
      • Clearview Medical Research LLC Site Number: 8400021
    • Lomita, California, United States, 90717-2101
      • Torrance Clinical Research Institute Site Number: 8400003
    • Santa Clarita, California, United States, 91321-2454
      • Center for Endocrinology Diabetes and Metabolic Disorders (CEDMD) - CAR Site Number: 8400026
    • Van Nuys, California, United States, 91405-3605
      • San Fernando Valley Health Institute - ClinEdge - PPDS Site Number: 8400023
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research LLC Site Number: 8400007
  • Florida
    • Clearwater, Florida, United States, 33756-2004
      • Innovative Research of West Florida Site Number: 8400016
    • Hialeah Gardens, Florida, United States, 33016
      • Evolution Clinical Trials Site number: 8400034
    • Miami, Florida, United States, 33135-1601
      • Wellness Research Center Inc - Miami Site Number: 8400010
    • Miami, Florida, United States, 33186
      • Med Research of Florida, LLC Investigator Site: 8400033
    • Orlando, Florida, United States, 32825
      • Florida Institute For Clinical Research LLC Site Number: 8400004
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University Site Number: 8400032
    • Atlanta, Georgia, United States, 30328-5532
      • Agile Clinical Research Trials, LLC Site Number: 8400001
    • Columbus, Georgia, United States, 31904
      • Centricity Research Site Number: 8400006
    • Lawrenceville, Georgia, United States, 30044-5896
      • Georgia Clinical Research Site Number: 8400009
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Endocrine and Metabolic Consultants Research Center Site Number: 8400031
  • Nevada
    • Las Vegas, Nevada, United States, 89113-3628
      • Diabetes, Obesity, Cardiovascular Clinical Specialists (DOCS) Site Number: 8400019
  • New York
    • New Windsor, New York, United States, 12553-7754
      • Mid Hudson Medical Research PLLC Site Number: 8400024
  • North Carolina
    • Morehead City, North Carolina, United States, 28557-3126
      • Lucas Research - Morehead City - HyperCore - PPDS Site Number: 8400008
  • Ohio
    • Maumee, Ohio, United States, 43537-1863
      • Advanced Medical Research Site Number: 8400012
  • Pennsylvania
    • Newport, Pennsylvania, United States, 17074
      • Capital Area Research LLC Site Number: 8400029
    • Philadelphia, Pennsylvania, United States, 19107-6810
      • Jefferson University Physicians (JUP) Site Number: 8400025
  • Tennessee
    • Bristol, Tennessee, United States, 37620-7353
      • Holston Medical Group PC Site Number: 8400018
  • Texas
    • El Paso, Texas, United States, 79935-4202
      • Frontier Medical Center Site Number: 8400035
    • Fort Worth, Texas, United States, 76132-4242
      • Diabetes and Thyroid Center of Fort Worth PLLC Site Number: 8400015
    • Houston, Texas, United States, 77054
      • Juno Research, LLC Site Number: 8400017
    • Houston, Texas, United States, 77074-1691
      • Reichman and Associates Site Number: 8400013
    • Lufkin, Texas, United States, 75904-3163
      • Texas Institute for Kidney and Endocrine Disorders Site Number: 8400027
    • Schertz, Texas, United States, 78154-1403
      • Northeast Clinical Research of San Antonio LLC Site Number: 8400022
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research Site Number: 8400030
  • Virginia
    • Suffolk, Virginia, United States, 23435-3763
      • David Ramstad Associates Research - IACT - HyperCore - PPDS Site Number: 8400005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is an adult aged ≥18 years at screening.
2. 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.
3. Has an HbA1c ≥7.5% and ≤10.5% at screening.
4. Has renal impairment, as defined by an eGFR (estimated glomerular filtration rate) of <60 mL/min/1.73m2 and ≥15 mL/min/1.73m2.
5. Has adequately controlled blood pressure with stable antihypertensive therapy at trial inclusion.
6. Is insulin-naïve, except for short use of insulin not exceeding 15 days during the last year before the screening period.
7. Is capable of understanding the written informed consent, and provides signed written informed consent.
8. Is willing and able to complete the electronic diary (eDiary) and agrees to comply with protocol requirements.
9. Is willing and able to fast without having administered study drug for scheduled site visits.

Exclusion Criteria:

1. Has initiated treatment with potential novel therapies like dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA.
2. Has a body mass index (BMI)* >45 kg/m² during the screening period.
3. 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).
4. 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.
5. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): August 4, 2023

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Renal Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: LPS17007; 2022-001485-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No