Healthy Participants
Conditions
Brief summary
To investigate the pharmacokinetics (PK) of rifabutin in subjects with hepatic impairment after single intravenous (IV) infusion of BV100
Detailed description
To investigate the pharmacokinetics (PK) of rifabutin and excipient in subjects with hepatic impairment after single intravenous (IV) infusion of BV100. In addition to investigate the safety and tolerability of BV100 in subjects with hepatic impairment and to investigate the PK of 25-deacetyl-rifabutin metabolite in subjects with hepatic impairment after single intravenous (IV) infusion of BV100
Interventions
DRUGBV100
Rifabutin for Infusion
Sponsors
Clinical Research Units Hungary
BioVersys AG
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
The main inclusion criteria will be: All participants (Groups 1-4): 1. Participants must provide written informed consent prior to any screening procedures being performed. 2. Male and non-child bearing potential females between 18 and 75 years of age, inclusive 3. Women of non-childbearing potential is defined as women who are physiologically and/or anatomically incapable of becoming pregnant, as now further described: * They are post-menopausal as evidenced by 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). * They have had bilateral surgical oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks prior. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment she is considered not of childbearing potential. 4. Participants must weigh at least 50.0 kg and must have a BMI within the range of 18.0 to 38.0 kg/m2, inclusive, for healthy participants at Screening. For hepatic impairment participants without overt ascites, the BMI should be within the range of 18 to 40 kg/m2. For hepatic impairment participants with overt ascites, the BMI should be within the range of 18 to 45 kg/m2 5. Participant is able to read, speak, and understand the local language, to understand and comply with the requirements of the study. 6. Must be a non-smoker or agree to smoke no more than 10 cigarettes or equivalent nicotine containing products per day and are committed not to increase the consumption during the study period Additional inclusion criteria for healthy participants (Group 1): 7. Each participant must match in age (+/- 10 years), gender, weight (+/- 20%), and smoking status to a participant in Groups 2, 3 and/or 4. 8. Seated vital signs must be within the following ranges at Screening and Baseline: * Body temperature, 35.0 to 37.5°C, inclusive * Systolic blood pressure, 89 to 140 mmHg, inclusive * Diastolic blood pressure, 50 to 90 mmHg, inclusive * Pulse rate, 40 to 100 bpm, inclusive 9. Healthy participants with no clinically significant abnormalities as determined by past medical history, physical examination, vital signs, ECG, and clinical laboratory test Additional inclusion criteria for mild, moderate and severe hepatic impairment participants (Groups 2-4): 10. Participants with Child-Pugh Clinical Assessment Score as calculated per the Child-Pugh classification. 11. Seated vital signs must be within the following ranges at Screening and Baseline: * Body temperature, 35.0 to 37.5°C, inclusive * Systolic blood pressure, 89 to 160 mmHg, inclusive * Diastolic blood pressure, 50 to 100 mmHg, inclusive * Pulse rate, 40 to 100 bpm, inclusive 12. Stable Child-Pugh status at Screening and Baseline visits 13. Participants with impaired hepatic function and other stable medical disorders such as diabetes, hypertension, hyperlipidemia, hypothyroidism etc., are eligible, as long as they are considered appropriate for enrollment, as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at Screening and Baseline
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the single dose pharmacokinetic profile of rifabutin | 15 days | Peak Plasma Concentration (Cmax) |
| To investigate the pharmacokinetics (PK) of rifabutin in participants with hepatic impairment | 15 days | Area under the plasma concentration versus time curve (AUC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the safety and tolerability of single intravenous ascending doses of BV100 assessed by the nature, occurrence, and severity of treatment-emergent adverse events | 31 Days | Safety and Tolerability |
| To determine the plasma concentration of the main metabolite 25-O-Desacetyl-Rifabutin in plasma in participants with hepatic impairment | 15 days | Pharmacokinetics |
| To determine the plasma concentration of DMI in plasma in subjects with hepatic impairment | 15 days | Pharmacokinetics |
Countries
Hungary
Outcome results
None listed