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

NCT05086107 | Completed Phase 1

• 1 other identifier: BV100-003
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the pharmacokinetics (PK) of rifabutin in subjects with renal impairment after single intravenous (IV) infusion of BV100

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (2)

• To investigate the pharmacokinetics (PK) of rifabutin in subjects with renal impairment

  Area under the plasma concentration versus time curve (AUC)

  96 hours

• To characterize the single dose pharmacokinetic profile of rifabutin

  Peak Plasma Concentration (Cmax)

  96 hours

Secondary Outcomes (2)

• 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

  7 days

• To determine the plasma concentration of the main metabolite 25-O-Desacetyl-Rifabutin in plasma in subjects with renal impairment

  96 hours

Study Arms (6)

Group 1

EXPERIMENTAL

subjects with mild renal impairment (eGFR: 60 to 89 mL/min)

Drug: BV100

Group 2

EXPERIMENTAL

subjects with moderate renal impairment (eGFRr: 30 to 59 mL/min)

Drug: BV100

Group 3

EXPERIMENTAL

subjects with severe renal impairment (eGFR: 15-29 mL/min)

Drug: BV100

Group 4

EXPERIMENTAL

subjects with normal renal function (eGFR: ≥ 90 mL/min)

Drug: BV100

Group 5

EXPERIMENTAL

subjects with end stage renal disease (ESRD) eGFR: \<15 mL/min requiring dialysis (with BV100 dosing and PK during the dialysis-free interval)

Drug: BV100

Group 6

EXPERIMENTAL

subjects with ESRD (eGFRr: \<15 mL/min) requiring dialysis (with BV100 dosing and PK on the day of dialysis)

Drug: BV100

Interventions

BV100 DRUG

Rifabutin for infusion

Also known as: Rifabutin for Infusion

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are able to understand and follow instructions during the study.
• Subjects who signed informed consent.
• 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 who underwent surgical sterilization
• female subjects who underwent hysterectomy
• female subjects with documented premature ovarian failure
• Weight within a BMI range of 19.0-35.0 kg/m2, range limits inclusive.
• Having had no febrile or infectious illness for at least 7 days prior to dosing.
• The subject will be available to complete the study.
• 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":
• Estimated glomerular filtration rate (eGFR) according to MDRD:
• ≥90 mL/min (normal renal function)
• 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":

You may not qualify if:

• Unwilling or unable to give informed consent.
• As a result of the medical screening process, the study physician considered the subject unfit for the study.
• Pregnant or lactating women or men with female partners who are lactating or are pregnant.
• 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.
• History of antibiotic-associated diarrhoea within one year.
• 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.
• 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.
• A positive screening serology test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)-1 and / or 2.
• Positive drugs-of-abuse or alcohol screen.
• History of epilepsy, other neurological disorders, or neuropsychiatric con-ditions.
• History of seizures.
• 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
• 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.
• 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'.
• 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).

Sponsors & Collaborators

• BioVersys AG: lead
• Clinical Research Units Hungary: collaborator

Study Sites (1)

CRU Hungary Kft., Early Phase Unit

Miskolc, H-3529, Hungary

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Rifabutin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: BV100 administered as a single intravenous infusion to subjects with varying degree of renal impairment and control volunteers with normal renal function.

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: October 20, 2021
• Study Start: October 8, 2021
• Primary Completion: May 30, 2022
• Study Completion: January 16, 2023
• Last Updated: January 18, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)