Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetics of BV100 in Male Subjects

NCT04636983 | Completed Phase 1 DMC

• 1 other identifier: BV100-01
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, single-centre, double-blind, randomised, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of single intravenous ascending doses of BV100 to healthy male subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• 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

  Safety and tolerability

  10 Days

Secondary Outcomes (2)

• To characterize the single dose pharmacokinetic profile of rifabutin: Area under the plasma concentration versus time curve (AUC)

  120 hours

• To characterize the single dose pharmacokinetic profile of rifabutin: Peak Plasma Concentration (Cmax)

  120 hours

Other Outcomes (2)

• To determine the urinary excretion of BV100: Cumulative amount excreted within 24 and 96 hours after start of infusion

  96 hours

• To determine the plasma concentration of the main metabolite 25-O-Desacetyl-Rifabutin in plasma

  5 days

Study Arms (2)

BV100

EXPERIMENTAL

BV100 intravenous infusion

Drug: BV100

Placebo

PLACEBO COMPARATOR

Saline intravenous infusion

Drug: Placebo

Interventions

BV100 DRUG

Rifabutin IV

BV100

Placebo DRUG

Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: • Healthy male subjects
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must be 18 to 55 years of age inclusive at the time of signing the informed consent.
• Subjects who are healthy as determined by the Investigator based on medical evaluation including medical history, physical and neurological examination, vital signs, ECG, and clinical laboratory tests at screening and on Day -1.
• Subjects are able to have an intravenous line placed.
• Body weight of at least 50 kg and BMI within the range of 19 to 30 kg/m2 (inclusive) at screening examination.
• Male subjects will be included in the study.
• Subjects must agree to the following from the time of the first dose until 3 months after the follow-up visit:
• use two acceptable methods of birth control with a female partner of child-bearing potential (barrier method combined with an additional highly effective contraceptive method). Barrier methods of contraception include condom or occlusive cap (diaphragm or cervical/vault caps). Highly effective contraception is defined in accordance with the Clinical Trial Facilitation Group (CTFG 2014 ) guidance and includes the following methods: implants, injectables, hormonal intrauterine device, combined hormonal contraceptives, sexual abstinence and vasectomized sexual partner.
• refrain from donating sperm.
• Prior to any clinical study specific procedure the subject provided written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Subjects must be able to read, write, and fully understand the German language.
• \. Prior to any clinical study specific procedure the subject provided written informed consent as described in Appendix 3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Subjects must be able to read, write, and fully understand the German language.

You may not qualify if:

• History of clinically relevant disease of any organ system that may interfere with the objectives of the study or provide a risk to the health of the subject.
• 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 conditions (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 outcome of the study.
• History of antibiotic associated diarrhoea within the last year.
• History of epilepsy, other neurological disorders, or neuropsychiatric conditions.
• Subjects with ECG abnormalities (history, or evidence of second-degree heart block of Mobitz type II, third degree heart block, or any abnormality considered relevant by the Investigator), QTcF \> 450 ms, PR \> 200 ms, or QRS duration \> 110 ms.
• Glomerular Filtration Rate (GFR) \< 90 mL/min/1.73m2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula. In case of a borderline result between ≥ 80 and \< 90 mL/min, Cystatin C will be determined in addition, and the subject will only be included if the Cystatin C value is below the upper limit of normal (ULN).
• Screening values other than AST, ALT, ALP, creatinine, for haematology, biochemistry, or urinalysis must not exceed the reference range. Minor deviations from normal are allowed, if they are not clinically significant.
• History of symptomatic, chronic or recurrent infection (e.g. nausea, vomiting, diarrhoea, infection with fever) or any viral (including symptomatic herpes zoster), bacterial (including upper respiratory infection), fungal (non-cutaneous) or parasitic infection within 30 days prior to admission to the clinical unit.
• Subjects who have received any prescribed systemic or topical medication within 4 weeks of the dose administration or within 5 times the half-life, whichever is longer, except for the occasional use of paracetamol (up to 2 g/day).
• Subjects who have used any non-prescribed systemic or topical medication (including dietary supplements, natural and herbal remedies) or megadose vitamins (i.e. 20 to 600 times the recommended daily supplement dose) within 7 days of the dose administration, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise safety.
• Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the first dose administration.
• Regular use of any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to the first admission to the clinical unit.
• Administration of live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study.
• Subjects who have participated in a clinical study involving administration of an investigational drug (new chemical entity) within the following time period prior to the first 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).
• Exposure to more than 4 new chemical entities in the last 12 months before the first dosing day in this study.

Sponsors & Collaborators

• BioVersys SAS: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Location

Study Officials

• Denis Strugala, MD

  Nuvisan GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 19, 2020
• Study Start: November 9, 2020
• Primary Completion: December 12, 2021
• Study Completion: January 20, 2022
• Last Updated: February 8, 2022

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)