Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients (START)

Martina McGrath, MD

Status and phase: Completed; Phase 2

Conditions: Kidney Transplant

Treatments: Diagnostic Test: eGFR reporting

Study type: Interventional

Funder types: Other

Identifiers

NCT05405556

2022P000454

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Patients and providers only aware of study eGFR values more than 25% below baseline

Experimental group

Description:

Any study-related eGFR value more than 25% below the baseline measurement will be reported to the patient and treating physician.

Treatment:

Diagnostic Test: eGFR reporting

Patients and providers aware of all study eGFR values

Other group

Description:

All study-related eGFR measurements will be reported to the treating physician and patient.

Treatment:

Diagnostic Test: eGFR reporting