Sicherheit und Verträglichkeit von Sotagliflozin bei Nierentransplantationsempfängern (START)
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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
Kontakte und Standorte
Studienorte
-
-
Massachusetts
-
Boston, Massachusetts, Vereinigte Staaten, 02115
- Brigham and Women's
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
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. |
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:
|
|
Sonstiges: Patients and providers aware of all study eGFR values
All study-related eGFR measurements will be reported to the treating physician and patient. |
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:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Reversibility of eGFR Changes
Zeitfenster: 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. |
16 weeks total
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Proportion of Patients Successfully Completing the Full Treatment Protocol, According to Randomized Groups
Zeitfenster: 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. |
16 weeks total
|
Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Safety Assessments
Zeitfenster: 4 weeks
|
- Acute changes in eGFR (baseline to 4 weeks) |
4 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- Longer-term changes in eGFR (baseline to 12 weeks and 4 weeks to 12 weeks) |
12 weeks
|
|
Safety Assessments
Zeitfenster: Weeks 12-16 (off-drug)
|
- Reversibility of changes in eGFR (12 to 16 weeks - after drug discontinuation) |
Weeks 12-16 (off-drug)
|
|
Safety Assessments
Zeitfenster: 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 |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- All adverse events (AEs) |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- All serious adverse events (SAEs) |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- Diarrhea |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- Infection requiring treatment with anti-microbials (including urogenital infection and urinary tract infections) |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- Severe hypoglycemia (event that requires assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions) |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- Diabetic ketoacidosis |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- Hyperkalemia (>5.5 mmol/L) |
12 weeks
|
|
Safety Assessments
Zeitfenster: 12 weeks
|
- Hypotension (symptomatic SBP <90 mmHg or hypotension requiring adjustment in blood pressure medications or treatment in an emergency or hospitalized setting) |
12 weeks
|
|
Tolerability Assessments
Zeitfenster: 12 weeks
|
- Proportion of participants able to complete the full 12 weeks of treatment, according to randomized arm |
12 weeks
|
|
Tolerability Assessments
Zeitfenster: 12 weeks
|
- Study medication discontinuation rates |
12 weeks
|
|
Tolerability Assessments
Zeitfenster: 12 weeks
|
- KDQOL-36 questionnaire |
12 weeks
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Martina M McGrath, MBBCh, Brigham and Women's Hospital
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Andere Studien-ID-Nummern
- 2022P000454
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
Only sharing of anonymized data will be considered as per approved protocol. Written requests for data sharing will be considered on a case-by-case basis from qualified external researchers, based on scientific merit.
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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