Pharmacokinetics and Safety of BV100 Administered as Single Intravenous Infusion to Subjects With Renal Impairment

Exclusion Criteria

• •1. Unwilling or unable to give informed consent.
• •2. As a result of the medical screening process, the study physician considered the subject unfit for the study.
• •3. Pregnant or lactating women or men with female partners who are lactating or are pregnant.
• •4. Known or suspected history of hypersensitivity to rifabutin or excipients or to drugs of a similar chemical class including rifampicin, rifapentine, rifaximin; history of allergic reactions leading to hospitalisation or any other allergic con-ditions (including drug allergies, asthma, eczema, anaphylactic reactions but excluding untreated, asymptomatic, seasonal allergies) which the Investigator considers may affect the safety of the subject and / or the outcome of the study.
• •5. History of antibiotic-associated diarrhoea within one year.
• •6. Subjects with significant ECG abnormalities (history, or evidence of sec-ond-degree heart block of Mobitz type II, third degree heart block, or any ab-normality considered relevant by the Investigator), QTcF \> 460 ms, PR \> 200 ms, or QRS duration \> 120 ms.
• •7. History of symptomatic, chronic or recurrent infection (e.g. nausea, vomit-ing, diarrhoea, infection with fever) or any viral, bacterial, fungal or parasitic infection within 30 days prior to admission to the clinical unit.
• •8. A positive screening serology test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)-1 and / or 2.
• •9. Positive drugs-of-abuse or alcohol screen.
• •10. History of epilepsy, other neurological disorders, or neuropsychiatric con-ditions.
• •11. History of seizures.
• •12. Subjects having used megadose vitamins (i.e. 20 to 600 times the recom-mended daily supplement dose) within 7 days prior to dosing, unless in the opinion of the study physician the medication does not interfere with the study procedures or compromise safety
• •13. Volunteers who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes, utilized within 30 days of IMP administration.
• •14. Regular use within 3 months of IMP administration of a CYP3A enzyme modifier - any inhibitor, moderate or strong inducer, and sensitive or moder-ately sensitive substrate, as listed in Section 11.3 'Prohibited concomitant med-ications'.
• •15. Volunteers who have participated in a clinical study involving administra-tion of an investigational drug within the following time period prior to the dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• •16. Volunteers who consume more than 21 units of alcohol per week, or who have a significant history of alcohol abuse (one unit of alcohol equals ½ pint \[285 mL\] of beer or lager, one glass \[125 mL\] of wine, or 30 mL of 40% of alcohol by volume distilled spirits).
• •17. Excessive consumption of caffeine- or xanthine-containing food or bever-ages (\> 5 cups of coffee a day or equivalent), or inability to stop consuming from 48 hours prior to study treatment administration.
• •18. Subjects who smoke more than 10 cigarettes a day.
• •19. Any use of drugs-of-abuse or alcohol abuse within 2 years prior to the first admission to the clinical unit.
• •20. Inability to understand or communicate reliably with the Investigator or considered by the Investigator to be unable to or unlikely to co-operate with the requirements of the study.
• •21. Any other conditions or factors which in the opinion of the Investigator may interfere with study conduct. Failure to satisfy the Investigator of fitness to participate for any other reason.
• •22. Any significant blood loss, donation of one unit (450 mL) of blood or more, or receipt of transfusion of any blood or blood products within 60 days, or plasma donation within 7 days prior to the first admission to the clinical study site.
• •23. Volunteers who are employees or immediate family members of the study site or Sponsor.
• •Control volunteers with normal renal function, in addition to criteria of "All subjects":
• •24. Supine systolic blood pressure \> 150 mmHg or \< 90 mmHg, or diastolic blood pressure \> 100 mmHg or \< 50 mmHg at Screening or on Day 1, prior to dosing (any abnormal blood pressure results may be repeated arbitrarily, and if the repeat result is within the normal range, it is not considered to have met the exclusion criterion). Pulse rate \> 100 or \< 50 beats per minute at Screening or on Day 1, prior to dosing.
• •25. Screening laboratory values should not exceed 1.5 x ULN, and the eventu-al deviation should be deemed as being clinically non-significant. Any abnor-mal value of these parameters may be repeated arbitrarily, and if the repeated result is within the allowed range, it is not considered to have met the exclusion criterion.
• •26. Volunteers who have received any new prescribed systemic or topical medication within 4 weeks of the first dose administration.
• •Renally impaired patient volunteers, in addition to criteria of "All subjects":
• •27. Acute renal failure (as judged by the Investigator).
• •28. History of kidney transplant regardless of functionality.
• •29. History of nephrectomy.
• •30. Start of any new medication or any changes to current dosages within 14 days prior to study drug administration.