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

Type 2 Diabetes Mellitus Clinical Trial

— TRENT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05552859
• Other study ID #: LPS17007
• Secondary ID: 2022-001485-35
• Status: Terminated
• Phase: Phase 4
• Start date: December 5, 2022
• Est. completion date: August 4, 2023

Study information

• Verified date: September 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 62
• Est. completion date: August 4, 2023
• Est. primary completion date: July 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Renal Impairment
• Renal Insufficiency
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Insulin glargine 300 U/mL
Insulin glargine 300 U/mL in the SoloStar pen, self-administered once daily for 24 weeks.
• Insulin degludec 100 U/mL
Insulin degludec 100 U/mL will be self- administered once daily for 24 weeks.

Locations

Country	Name	City	State
Czechia	Diacentrum Brandys n. L. Site Number: 2030004	Brandýs Nad Labem-Stará Boleslav
Czechia	Diabetologicka, interni a obezitologicka ambulance Site Number: 2030005	Jílové U Prahy
Czechia	Diabetologie MUDr. Tomas Edelsberger Site Number: 2030001	Krnov	Moravskoslezský Kraj
Czechia	Agentura Science Pro spol. s.r.o.Site Number: 2030002	Olomouc	Olomoucký Kraj
Czechia	Institut Klinicke A Experimentalni Mediciny Site Number: 2030006	Prague	Praha, Hlavní Mesto
Czechia	Fakultni nemocnice Kralovske Vinohrady Site Number: 2030007	Praha
Hungary	Csolnoky Ferenc Korhaz Site Number: 3480005	Balatonfüred	Veszprém
Hungary	Magyar Honvédség Egészségügyi Központ Site Number: 3480003	Budapest
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház Site Number: 3480004	Kaposvár
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Site Number: 3480006	Nyíregyháza	Szabolcs-Szatmár-Bereg
Hungary	Markusovszky Egyetemi Oktatókórház Site Number: 3480001	Szombathely	Vas
Hungary	Zala Megyei Szent Rafael Korhaz Site Number: 3480002	Zalaegerszeg	Zala
Poland	NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Site Number: 6160001	Czestochowa	Slaskie
Poland	NZOZ Gdanska Poradnia Cukrzycowa Sp. z o.o. Site Number: 6160014	Gdansk	Pomorskie
Poland	Zaklad Opieki Medycznej "Sanatio" Sp.z o.o. - Osrodek Leczenia Schorzen Cywilizacyjnych Site Number: 6160016	Kraków	Malopolskie
Poland	ETG Lodz Site Number: 6160018	Lódz
Poland	Gabinet Lekarski Malgorzata Saryusz-Wolska Site Number: 6160017	Lódz
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Przychodnia Specjalistyczna Medica Site Number: 6160008	Lublin	Lubelskie
Poland	Specjalistyczna Praktyka Lekarska Site Number: 6160004	Lubliniec	Slaskie
Poland	Centrum Medyczne OMEDICA Site Number: 6160013	Poznan	Wielkopolskie
Poland	Praktyka Lekarska Ewa Krzyzagórska Site Number: 6160014	Poznan
Poland	KO-MED Centra Kliniczne Sp. z o.o. Site Number: 6160010	Pulawy	Lubelskie
Poland	Prywatny Gabinet Lekarski Centrum Medyczne Diabetika Dorota Mlodawska-Choluj Site Number: 6160015	Radom	Mazowieckie
Poland	Prywatny Gabinet Lekarski, Centrum Medyczne "Diabetika" Site Number:6160002	Radom
Poland	ETG Skierniewice - PPDS Site Number: 6160006	Skierniewice
Poland	KO-MED Centra Kliniczne Sp. z o.o. Site Number:6160011	Staszów	Swietokrzyskie
Poland	Centralny Szpital Kliniczny MSW Site Number: 6160005	Warszawa	Mazowieckie
Poland	NBR Polska Site Number: 6160003	Warszawa	Mazowieckie
Poland	Regionalna Poradnia Diabetologiczna - Wroclaw Site Number: 6160009	Wroclaw	Dolnoslaskie
Poland	KO-MED Centra Kliniczne Sp. z o.o. Site Number: 6160012	Zamosc	Lubelskie
Serbia	Clinical Hospital Centar Zvezdara Site Number: 6880001	Belgrade
Serbia	University Clinical Center of Serbia - PPDS Site Number: 6880003	Belgrade
Serbia	University Clinical Center of Serbia - PPDS Site Number: 6880004	Belgrade
Serbia	University Clinical Center Nis Site Number: 6880002	Niš
Serbia	University Clinical Center Nis Site Number: 6880005	Niš
Serbia	Health Center Zajecar Site Number: 6880006	Zajecar
United States	Agile Clinical Research Trials, LLC Site Number: 8400001	Atlanta	Georgia
United States	Emory University Site Number: 8400032	Atlanta	Georgia
United States	Holston Medical Group PC Site Number: 8400018	Bristol	Tennessee
United States	American Clinical Trials Site Number: 8400014	Buena Park	California
United States	Clearview Medical Research LLC Site Number: 8400021	Canyon Country	California
United States	Innovative Research of West Florida Site Number: 8400016	Clearwater	Florida
United States	Centricity Research Site Number: 8400006	Columbus	Georgia
United States	Frontier Medical Center Site Number: 8400035	El Paso	Texas
United States	Diabetes and Thyroid Center of Fort Worth PLLC Site Number: 8400015	Fort Worth	Texas
United States	Evolution Clinical Trials Site number: 8400034	Hialeah Gardens	Florida
United States	Juno Research, LLC Site Number: 8400017	Houston	Texas
United States	Reichman and Associates Site Number: 8400013	Houston	Texas
United States	Diabetes, Obesity, Cardiovascular Clinical Specialists (DOCS) Site Number: 8400019	Las Vegas	Nevada
United States	Georgia Clinical Research Site Number: 8400009	Lawrenceville	Georgia
United States	Torrance Clinical Research Institute Site Number: 8400003	Lomita	California
United States	Texas Institute for Kidney and Endocrine Disorders Site Number: 8400027	Lufkin	Texas
United States	Advanced Medical Research Site Number: 8400012	Maumee	Ohio
United States	Med Research of Florida, LLC Investigator Site: 8400033	Miami	Florida
United States	Wellness Research Center Inc - Miami Site Number: 8400010	Miami	Florida
United States	Lucas Research - Morehead City - HyperCore - PPDS Site Number: 8400008	Morehead City	North Carolina
United States	Mid Hudson Medical Research PLLC Site Number: 8400024	New Windsor	New York
United States	Capital Area Research LLC Site Number: 8400029	Newport	Pennsylvania
United States	Florida Institute For Clinical Research LLC Site Number: 8400004	Orlando	Florida
United States	Jefferson University Physicians (JUP) Site Number: 8400025	Philadelphia	Pennsylvania
United States	Endocrine and Metabolic Consultants Research Center Site Number: 8400031	Rockville	Maryland
United States	Center for Endocrinology Diabetes and Metabolic Disorders (CEDMD) - CAR Site Number: 8400026	Santa Clarita	California
United States	Northeast Clinical Research of San Antonio LLC Site Number: 8400022	Schertz	Texas
United States	Consano Clinical Research Site Number: 8400030	Shavano Park	Texas
United States	David Ramstad Associates Research - IACT - HyperCore - PPDS Site Number: 8400005	Suffolk	Virginia
United States	San Fernando Valley Health Institute - ClinEdge - PPDS Site Number: 8400023	Van Nuys	California
United States	Chase Medical Research LLC Site Number: 8400007	Waterbury	Connecticut
United States	Yuma Clinical Trials, LLC Site Number: 8400028	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Czechia,  Hungary,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in the mean change from baseline to Week 24 in HbA1c level (Gla-300 vs IDeg-100)		Baseline to 24 weeks
Secondary	Change in Fasting Plasma Glucose (FPG) from baseline to Week 24		Baseline to 24 weeks
Secondary	Change in fasting Self-Measured Plasma Glucose (SMPG) from baseline to Week 24		Baseline to 24 weeks
Secondary	Change in 7-point SMPG profiles from baseline to Week 24, per time point within 24-hour period		Baseline to 24 weeks
Secondary	Percentage of participants reaching HbA1c target of <7.0% at Week 24		At week 24
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)