The aim of this study is to test the hypothesis that dapagliflozin (SGLT2 inhibitor) and SC0062 (ERA) combination therapy augments nephroprotection and mitigates fluid retention and ketogenesis in people with T1D through complementary and synergistic mechanisms of actions.
A phase 2, multicenter, randomized, open-label, cross-over trial will be conducted in male or female individuals (N=36) diagnosed with type 1 diabetes at least 6 months prior to informed consent aged between 18 and 65 years, Body Mass Index (BMI) ≥ 21 kg/m2, urinary albumin: creatinine ratio ≥ 50 mg/g and \< 3000 mg/g, eGFR \> 30 and \<90 mL/min/1.73 m2 and HbA1c \> 6.5 and \<10.5%. Patients have to be on stable RAAS inhibition for at least 4 weeks prior to screening. The study will consist of a screening visit, a 4-week run-in phase. After the run-in phase, the participant will be randomized to treatment of SC0062, dapagliflozin, or their combination in random order. The duration of each treatment period is 4 weeks with study visits scheduled at 2 and 4 weeks in each treatment period. At the end of each treatment period patients proceed to a 4 weeks wash-out phase to study off drug effects. The total duration of the study for each participant after randomization is thus 24 weeks Interventions SC0062 10mg twice daily (20mg/day); dapagliflozin 5mg once daily; combination of SC0062 10mg twice daily and dapagliflozin 5mg once daily.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
5 mg/day as a tablet
20 mg/day, twice daily, capsule
20 mg/day SC0062 10 mg twice daily as a capsule in combination with 5 mg/day dapagliflozin 5 mg as a tablet
Steno Diabetes Center Aarhus
Aarhus, Denmark
Steno Diabetes Center Copenhagen
Copenhagen, Denmark
Regionshospitalet Gødstrup
Herning, Denmark
University of Helsinki
Helsinki, Uusimaa, Finland
Change from baseline in Urine Albumin-Creatinine Ratio (UACR)
Primary: change from baseline in Urine Albumin-Creatinine Ratio (UACR) when treated with SC0062 alone versus combination of dapagliflozin and SC0062.
Time frame: 4 weeks
Change from baseline in mGFR
Glomerular Filtration Rate (GFR) using iohexol clearance techniques.
Time frame: 4 weeks
Change in biomarkers of fluid retention
Change from baseline biomarkers of fluid retention (body weight, hemoglobin, N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP))
Time frame: 4 weeks
Change in biomarkers of fluid retention
Change from baseline biomarkers of fluid retention (Body Weight)
Time frame: 4 weeks
Change in biomarkers of fluid retention
Change from baseline biomarkers of fluid retention (hemoglobin)
Time frame: 4 weeks
Change in biomarkers of fluid retention
Change from baseline biomarkers of fluid retention (N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP))
Time frame: 4 weeks
Change from baseline Extracellular Volume (ECV)
Extracellular volume (ECV) using iohexol clearance techniques and bioimpedance spectroscopy.
Time frame: 4 weeks
Change from baseline blood pressure
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Turku University Hospital
Turku, Finland
Amsterdam University Academic Center
Amsterdam, North Holland, Netherlands
University Medical Center Groningen
Groningen, Provincie Groningen, Netherlands
Change in blood pressure as measure in mmHg
Time frame: 4 weeks