| Eligibility |
Inclusion Criteria:
1. Subjects who are able to understand and follow instructions during the study.
2. Subjects who signed informed consent.
3. Male subjects =18 and =75 years of age; female subjects =18 and =75 years of age of
non-childbearing potential, defined as follows:
- female subjects 50 years of age or older, in menopause for 24 consecutive months,
and not receiving any hormone replacement therapy within 24 months prior to
inclusion into the study
- female subjects who underwent surgical sterilization
- female subjects who underwent hysterectomy
- female subjects with documented premature ovarian failure
4. Weight within a BMI range of 19.0-35.0 kg/m2, range limits inclusive.
5. Having had no febrile or infectious illness for at least 7 days prior to dosing.
6. The subject will be available to complete the study.
7. The subject commits to comply with the restrictions and requirements of the protocol
and, in the opinion of the study physician, will be able to complete the study.
Control volunteers with normal renal function, in addition to criteria of "All
subjects":
8. Estimated glomerular filtration rate (eGFR) according to MDRD:
- =90 mL/min (normal renal function)
9. Control subjects have to be in good health or in stable condition, in the opin-ion of
the study physician, as determined by medical history, ECG, vital signs, physical
examination, and clinical laboratory tests. Subjects having chronic conditions should
have an onset of at least 3 months prior to Screening, clini-cally stable, and
well-controlled.
Renally impaired patient volunteers, in addition to criteria of "All subjects":
10. Estimated glomerular filtration rate (eGFR) according to MDRD:
- 60-89 mL/min (mild renal impairment)
- 30-59 mL/min (moderate renal impairment)
- 15-29 mL/min (severe renal impairment)
- <15 mL/min (requiring dialysis)
11. Stable renal impairment, defined as no clinically significant change in dis-ease
status within 2 weeks from Screening, as judged by the Investigator.
12. Subjects with systolic blood pressure = 90 mmHg and diastolic blood pressure = 50
mmHg.
13. Patients with chronic diseases / conditions other than renal impairment can be
included, provided that these diseases / conditions are stable, well-controlled, and
do not interfere with the study objectives or the subject's over-all safety, as judged
by the Investigator.
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.
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