| Eligibility |
Inclusion Criteria - Patients must meet all of the following inclusion criteria to be
enrolled in this study.
1. Men or women 60 years of age or older
OR
Age 18 - 59 years WITH at least one of the following comorbidities:
- BMI greater than or equal to 35
- Diabetes
- Asthma/ Chronic Obstructive Pulmonary Disease (COPD)
- Previous Myocardial Infarction
- Previous Stroke/ Cerebrovascular Accident (CVA)
- Hypertension/ Atherosclerosis/ Peripheral Vascular Disease
- Smoking and/or vaping
- Other conditions associated with senescent cell accumulation (i.e. previous
chemotherapy or radiation)
2. SpO2 greater than or equal to 85% (on room air or less than or equal to 2 L of
supplemental oxygen)
3. Willing and able to provide written informed consent or have a legally authorized
representative (LAR) who will provide informed consent
4. SARS-CoV-2 infection confirmed by PCR test at Mayo Clinic (or other CLIA certified)
laboratory within 10 days prior to randomization.
Exclusion Criteria - Patients who meet any of the following exclusion criteria are not to
be enrolled in this study.
General Exclusion Criteria
1. Presence of any condition that the Investigator or the subject's attending physician
believes would put the subject at risk or would preclude the patient from successfully
completing the trial
2. Pregnant and/or lactating. Women of childbearing potential (WCBP) must have a negative
pregnancy test within 72 hours prior to randomization
3. WCBP who are unwilling to abstain from sex or use an adequate method of contraception
from the time of the first IP administration through 48 hours after the last IP
administration
4. Men who are unwilling to abstain from sex with WCBP or use an adequate method of
contraception from the time of the first IP administration through 48 hours after the
last IP administration
Laboratory Exclusion Criteria
5. Total bilirubin >3X upper limit of normal or as per clinical judgment.
6. Serum aspartate transaminase (AST) or alanine aminotransferase (ALT) >4x the upper
limits of normal or as per clinical judgment.
7. Hemoglobin <7 g/dL; white blood cell count = 2,000/mm3 (< or = 2.0 x 109/L) or > or =
20,000/mm3 (> or = 20 x 109/L); platelet count < or = 40,000/µL (< or = 40 x 109/L);
absolute neutrophil count < or = 1 x 109/L; lymphocyte count <0.3 x 109/L at screening
or as per clinical judgment.
8. Unstable (as per clinical judgment) major cardiovascular, renal, endocrine,
immunological, or hepatic disorder.
9. eGFR <25 ml/ min/ 1.73 m2 or as per clinical judgment.
10. Plasma and/or serum glucose >300 or as per clinical judgment.
Clinical History Exclusion Criteria
11. Human immunodeficiency virus infection.
12. Known active hepatitis B or C infection.
13. Invasive fungal infection.
14. Uncontrolled (as per clinical judgement) pleural/pericardial effusions or ascites.
15. New/active invasive cancer except non-melanoma skin cancers.
Medication Exclusion Criteria (See Appendices 1-3 for additional information)
16. Known hypersensitivity or allergy to Fisetin.
17. Patients currently using medications which utilize CYP450 2C9 for metabolism. These
medications include: Fosphenytoin, Phenytoin, Warfarin, Glimepiride, Diclofenac,
Bosentan, and Glyburide. Patients taking any of these medications may participate if
the medications can be held immediately before the 1st IP administration until at
least 10 hours after the last (2nd) IP administration and the patient is otherwise
eligible.
18. Patients currently using medications which utilize CYP2C9, CYP2C19, CYP1A2, OATP1B1.
These medications include: Olanzapine, Clozapine, Theophylline, Tizanidine, Warfarin,
Rameltoen, Tacrine, Duloxetine, Mexiletine, Riluzole, and Atomoxetine. Patients taking
any of these medications may participate if the medications can be held immediately
before the 1st IP administration until at least 10 hours after the last (2nd) IP
administration and the patient is otherwise eligible.
19. Patients currently using medications which are strong inhibitors of CYP3A4. These
medications include: Atazanavir, Ceritinib, Clarithromycin, Darunavir, Idelalisib,
Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mefipristone, Nefazodone,
Nelfinavir, Ombitasivir-paritaprevir-ritonivir,
Ombitasivir-paritaprevir-ritonivir-plus dasabuvir, Posaconazole, Saquinavir,
Telithromycin, Tucatinib, and Voriconazole. Patients taking any of these medications
may participate if the medications can be held immediately before the 1st IP
administration until at least 10 hours after the last (2nd) IP administration and the
patient is otherwise eligible.
20. Patients currently using antifungals. If antifungals are absolutely necessary from an
infectious disease perspective, then they will be allowed only if the levels are
subtherapeutic or therapeutic.
21. Patients taking any of these medications may participate if the medications can be
held immediately before the 1st IP administration until at least 10 hours after the
last (2nd) IP administration and the patient is otherwise eligible:
- Cardiac: digoxin, flecainide, amiodarone
- Psychiatric: lithium, thioridazine
- Neurologic: carbamazepine, phenobarbital
- Antimicrobial/fungal: aminoglycosides (e.g. amikacin, gentamicin, kanamycin,
neomycin, netilmicin, paromomysin, streptomycin, tobramycin), rifampin
- Anticoagulants/ Antiplatelets: warfarin
- Others: methotrexate, nitroglycerin, St. John's wort, tyrosine kinase inhibitors,
tacrine, diclofenac
22. Participation in other clinical trials involving treatment for SARS-CoV-2. (unless
reviewed and approved by the Principal Investigator). Note that institutional standard
of care treatment of SARS-CoV-2 including glucocorticoids, hydroxychloroquine,
azithromycin, remdesivir, anti-spike antibodies, and/or convalescent plasma are not
excluded from the study.
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