Can common kidney drugs weaken the smallpox antiviral TPOXX?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Each subject must meet all of the following criteria to be enrolled in this study: 1. Subject is male or female 18 to 50 years of age, inclusive. 2. Phosphorus levels within normal laboratory reference range. 3. Women of childbearing potential have a negative human chorionic gonadotropin pregnancy test (serum) at the screening visit and a confirmatory negative serum pregnancy test on Day -1 of each period before receipt of study drug, and meet one of the following criteria: 1. The subject or their partner has undergone surgical sterilization 2. The subject is postmenopausal, defined as 12 consecutive months with no menses without an alternative medical cause and has a documented plasma follicle-stimulating hormone level \>40 IU/mL Exclusion Criteria: Subjects meeting any of the following criteria will be excluded from the study: 1. Subject is a female who is pregnant or breastfeeding or planning to become pregnant within 3 months after the last dose of study drug. 2. Subject has a history of any clinically significant conditions including: * Asthma treated with oral systemic steroids within the past 6 months * Diabetes mellitus (type 1 or 2), with the exception of gestational diabetes * Hypertension that is poorly controlled (repeat readings \>140 mm Hg systolic and/or \>90 mm Hg diastolic) * Thyroidectomy or thyroid disease that required medication within the past 12 months * Serious angioedema episodes within the previous 3 years or requiring medication in the previous 2 years * Head trauma resulting in a diagnosis of traumatic brain injury other than concussion * Frequent episodes of headache. 3. Subject has received treatment in another clinical study of an investigational drug (or medical device) within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug. 4. Subject has a history of relevant drug and/or food allergies (ie, allergy to TPOXX or excipients, or any significant food allergy that could preclude a standard diet in the study site). 5. Subject has any condition possibly affecting drug absorption (eg, previous surgery on the gastrointestinal tract, including removal of parts of the stomach, bowel, liver, gallbladder, or pancreas, with the exception of appendectomy). 6. Subject has evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of the first dose of study drug), hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease. Exceptions to these criteria (eg, stable, mild joint disease unassociated with collagen vascular disease) may be made following discussions with the medical monitor. 7. Subject has a history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or risk factors for torsades de pointes (eg, heart failure, hypokalemia). 8. Subject has a family history of sudden cardiac death not clearly due to acute myocardial infarction. 9. Subject has a seizure disorder or history of seizures (does not include childhood febrile seizures) or a past history that increases seizure risks such as significant head injury that caused loss of consciousness or other changes in the subject's daily function, concussion, stroke, central nervous system infection or disease, or alcohol or drug abuse or family history of idiopathic seizures. 10. Subject has a history of a peptic ulcer or significant gastrointestinal bleeding. 11. Subject has a bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with blood draws. 12. Subject has a malignancy that is active, or treated malignancy for which there is not reasonable assurance of sustained cure, or malignancy that is likely to recur during the period of the study (subject should be in complete remission for at least 5 years). 13. Subject has neutropenia or other blood dyscrasia determined to be clinically significant by the investigator. 14. Subject has used any of the following prohibited medications from within 7 days (or 5 half lives, whichever is longer) before the first dose of study drug: antidiabetic medication; anticoagulants; anticonvulsants; substrates of the breast cancer resistance protein transporter including methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, and topotecan; substrates of CYP2C8 including repaglinide, paclitaxel, Montelukast, pioglitazone, rosiglitazone; and substrates of CYP2C19 including S-mephenytoin, clobazam, diazepam, rabeprazole, voriconazole, lansoprazole, and omeprazole. Medications not listed here that are known (or thought) to be CYP3A4 substrates may be allowed at the investigator's discretion, after consultation with the medical monitor, if administration poses little to no risk to the subject. 15. Subject has a history of drug or alcohol abuse or dependency within the last year before screening. 16. Subject has a current or recent (\<30 days before screening) history of clinically significant bacterial, fungal, or mycobacterial infection. 17. Subject has a current clinically significant viral infection. 18. Subject has a known clinically significant chronic viral infection (eg, human T cell lymphotropic virus I or II). 19. Subject has consumed grapefruit or grapefruit juice, Seville orange or Seville orange containing products (eg, marmalade), or caffeine- or xanthine containing products within 48 hours before the first dose of study drug. 20. Subject has used any prescription (excluding hormonal birth control) or over the counter medication (including herbal or nutritional supplements) within 14 days before the first dose of study drug. 21. Subject demonstrates long-term use (≥14 consecutive days) of glucocorticoids including oral or parenteral prednisone or equivalent (\>20 mg total dose per day) or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 1 month (low-dose \[≤800 mcg/day of beclomethasone dipropionate or equivalent\] inhaled and topical steroids are allowed). 22. Subject has donated \>450 mL blood or blood components within 30 days before the first dose of study drug. The investigator should instruct subjects who participate in this study to not donate blood or blood components for 4 weeks after the completion of the study. 23. Subject is a smoker or has used nicotine or nicotine containing products (eg, cigarettes, electronic vapor cigarettes, cigars, chewing tobacco, snuff, nicotine patches, or nicotine gum) within 6 months before the first dose of study drug. 24. Subject has consumed pomegranate or pomegranate juice, pomelo fruits or pomelo juice, or alcohol within 72 hours before the first dose of study drug. 25. Subject reports participation in strenuous activity or contact sports within 24 hours before the first dose of study drug. 26. Subject has known hepatitis B or C infection or positive test for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus type 1 or 2 antibodies at screening. 27. Subject has a positive test result for amphetamines (including methamphetamines and ecstasy/methylenedioxymethamphetamine), barbiturates, benzodiazepines, cannabinoids (including tetrahydrocannabinol), cocaine metabolites, opiates (including heroin, codeine, and oxycodone), or alcohol at screening or check-in. 28. Subject has any of the following laboratory test results within 28 days before the first dose of study drug: * Estimated serum creatinine clearance (Cockcroft-Gault) \<70 mL/min * Creatinine in males \>1.7 mg/dL and in females \>1.4 mg/dL (1.3 times the upper laboratory reference range) * Hemoglobin ≤10% of the lower laboratory reference range * White blood cell count considered to be clinically significant by the investigator * Absolute neutrophil count \<1000 cells/mm3 * Platelets not within ±10% of laboratory reference range * Alanine aminotransferase \>2.0 times above the upper laboratory reference range * Aspartate aminotransferase \>2.0 times above the upper laboratory reference range * Alkaline phosphatase \>20% above the upper laboratory reference range * Hemoglobin A1c ≥7.0% * Cholesterol ≥300 mg/dL and low density lipoprotein ≥190 mg/dL. 29. Subject has a blood pressure considered to be clinically significant by the investigator. Blood pressure may be retested twice in the sitting position at 5 minute intervals. 30. Subject has a resting heart rate of \<40 beats per minute or \>110 beats per minute at screening. 31. Subject has an abnormal ECG at screening that is determined by the investigator to be clinically significant. 32. Male subject has a QT interval corrected using Fridericia's formula (QTcF) \>450 ms or female subject has a QTcF \>470 ms at screening or Day -1. 33. In the opinion of the investigator, the subject is not suitable for entry into the study.