START: Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Patients and providers only aware of study eGFR values more than 25% below baseline Any study-related eGFR value more than 25% below the baseline measurement will be reported to the patient and treating physician. |
Diagnostic Test: eGFR reporting
To test the proportion of patients successfully completing the protocol according to different eGFR reporting strategies, randomization in a 1:1 fashion at the patient level (n=50) will occur as follows:
only study-related eGFR values >25% below baseline will be reported to patients and providers
all study-related eGFR will be provided to patients and providers
|
| Other: Patients and providers aware of all study eGFR values All study-related eGFR measurements will be reported to the treating physician and patient. |
Diagnostic Test: eGFR reporting
To test the proportion of patients successfully completing the protocol according to different eGFR reporting strategies, randomization in a 1:1 fashion at the patient level (n=50) will occur as follows:
only study-related eGFR values >25% below baseline will be reported to patients and providers
all study-related eGFR will be provided to patients and providers
|
Outcome Measures
Primary Outcome Measures
- Reversibility of eGFR changes [16 weeks total]
Following 12 weeks of open-label drug treatment, participants will stop drug and be followed for a further four weeks (16 weeks total). Reversibility will be assessed as the proportion of patients who return to baseline eGFR (+/- 10%) by the end of the 4-week off-treatment period.
Secondary Outcome Measures
- Proportion of patients successfully completing the full treatment protocol, according to randomized groups [16 weeks total]
Following 12 weeks of open-label drug treatment, participants will stop drug and be followed for a further four weeks. The proportion of patients completing the full 16 weeks will be compared according to randomized groups.
Other Outcome Measures
- Safety Assessments [4 weeks]
- Acute changes in eGFR (baseline to 4 weeks)
- Safety Assessments [12 weeks]
- Longer-term changes in eGFR (baseline to 12 weeks and 4 weeks to 12 weeks)
- Safety Assessments [Weeks 12-16 (off-drug)]
- Reversibility of changes in eGFR (12 to 16 weeks - after drug discontinuation)
- Safety Assessments [12 weeks]
- Acute Kidney Injury (>50% increase in serum creatinine/40% decline in eGFR within one week), which will be assessed throughout the on-drug period of 12 weeks
- Safety Assessments [12 weeks]
- All adverse events (AEs)
- Safety Assessments [12 weeks]
- All serious adverse events (SAEs)
- Safety Assessments [12 weeks]
- Diarrhea
- Safety Assessments [12 weeks]
- Infection requiring treatment with anti-microbials (including urogenital infection and urinary tract infections)
- Safety Assessments [12 weeks]
- Severe hypoglycemia (event that requires assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions)
- Safety Assessments [12 weeks]
- Diabetic ketoacidosis
- Safety Assessments [12 weeks]
- Hyperkalemia (>5.5 mmol/L)
- Safety Assessments [12 weeks]
- Hypotension (symptomatic SBP <90 mmHg or hypotension requiring adjustment in blood pressure medications or treatment in an emergency or hospitalized setting)
- Tolerability Assessments [12 weeks]
- Proportion of participants able to complete the full 12 weeks of treatment, according to randomized arm
- Tolerability Assessments [12 weeks]
- Study medication discontinuation rates
- Tolerability Assessments [12 weeks]
- KDQOL-36 questionnaire
Eligibility Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Brigham and Women's Hospital
Investigators
- Principal Investigator: Martina M McGrath, MBBCh, Brigham and Women's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- 2022P000454