Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients

This is an investigator-initiated, randomized controlled trial in adult KTRs (N=50) with stable allograft function to assess: 1) the reversibility of the expected acute changes in eGFR with sotagliflozin (donated by Lexicon); 2) proportion of patients completing the protocol according to different eGFR reporting strategies (using a predefined algorithm to manage the expected pharmacological effect of sotagliflozin on eGFR); 3) safety and tolerability of sotagliflozin.


Eligibility Criteria:
Inclusion Criteria:

* Adults ≥18 years
* Recipients of kidney transplant with stable eGFR\*
* eGFR-creatinine (CKD-EPI 2021) ≥25 mL/min/1.73 m2
* Informed consent

  * Stable eGFR will be ascertained by careful chart review establishing that the patient's current graft has been functioning for at least 12 months post-transplantation, patients have not been treated for acute rejection within the prior 3 months, and a creatinine-based eGFR is stable (two consecutive measurements separated by at least 28 days within 5 mL/min/1.73 m2) and ≥25 mL/min/1.73 m2.

Exclusion Criteria:

* Recurrent urinary tract infections (\>2 episodes/year or antibiotic prophylaxis)
* Biopsy-proven acute rejection within 12 weeks
* Screening serum potassium \>5.5 mmol/L
* Uncontrolled hypertension (systolic blood pressure \>180/100 mmHg)
* New York Heart Association (NYHA) Class IV HF
* Myocardial infarction, unstable angina, revascularization procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 12 weeks
* History of diabetic ketoacidosis
* Type 1 Diabetes Mellitus
* Hereditary glucose-galactose malabsorption or primary renal glucosuria
* Liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis); Alanine aminotransferase (ALT) levels \>2.0 times the upper limit of normal (ULN) or total bilirubin \>1.5 times the ULN, unless consistent with Gilbert's disease
* Malignancy within 5 years (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)
* Human immunodeficiency virus antibody positive
* Major surgery within 12 weeks
* Atraumatic amputation within past 12 months of screening, or an active skin ulcer, osteomyelitis, gangrene, or critical ischemia of the lower extremity within 6 months of screening
* Combination use of ACEi and ARB
* Current use of an SGLT2 inhibitor (within 12 weeks prior to randomization)
* Known allergies, hypersensitivity, or intolerance to SGLT2i or its excipients
* Digoxin plasma level \>1.2 ng/mL
* Clofibrate, fenofibrate, dronedarone, or ranolazine treatment that has not been at a stable dose in the 30 days prior to screening or randomization, or a dose adjustment is expected
* Received an active investigational drug (including vaccines) other than a placebo agent, or used an investigational medical device within 12 weeks before Day 1/baseline
* Pregnant or breast-feeding or planning to become pregnant or breast-feed during the study
* Women of childbearing potential not willing to use a highly-effective method(s) of birth control, or who are unwilling or unable to be tested for pregnancy
* Any condition that in the opinion of the investigator would make participation not in the best interest of the subject