Effect of BV100 on polymyxin B levels in healthy adults

BV100-011 A Single Centre, Open-label, 2-period Fixed-sequence, Phase I Clinical Study to Evaluate the Effect of BV100 on the Pharmacokinetics of Polymyxin B in Healthy Volunteers

This study will test whether giving BV100 changes how polymyxin B behaves in the bodies of healthy adults.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: BioVersys AG (Industry-sponsored)
• Locations: 1 site (Vienna)
• Trial ID: NCT07580586 on ClinicalTrials.gov

What this trial studies

This is an open-label, fixed-sequence Phase 1 pharmacokinetic study in healthy adult volunteers designed to measure whether repeated IV doses of BV100 alter the blood levels of a single IV dose of polymyxin B. Sixteen participants are enrolled in two sequential groups of eight; each participant receives polymyxin B alone in Period 1, then BV100 alone and the combination in Period 2. Group 1 receives infusions diluted in 500 mL saline and Group 2 in 250 mL saline to assess any effect of infusion volume on drug behavior. Blood samples for pharmacokinetic analysis will be collected around dosing to compare polymyxin B concentrations with and without BV100.

Who should consider this trial

Good fit: Healthy men and non-childbearing-potential women aged 18–55 with BMI 19.0–30.0 kg/m2 and eGFR > 60 mL/min/1.73 m2 who can give informed consent are eligible.

Not a fit: People with active infections, children, pregnant or lactating women, those over 55 years, or with significant kidney impairment are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could guide safe combined dosing and support development of BV100 plus polymyxin B regimens for serious Gram-negative infections.

How similar studies have performed: Preclinical laboratory data show strong synergy between BV100 and polymyxin B against carbapenem-resistant Acinetobacter baumannii, but human PK interaction data are novel.

Eligibility criteria

Main Inclusion Criteria:

1. Participants who were able to understand and follow instructions during the study.
2. Participants who signed informed consent.
3. Male participants ≥ 18 and ≤ 55 years of age; female participants ≥ 18 and ≤ 55 years of age of non-childbearing potential and non-lactating, with absence of childbearing potential defined as follows:

   1. Female participants 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
   2. Female participants who underwent surgical sterilization
   3. Female participants who underwent hysterectomy
   4. Female participants with documented premature ovarian failure
4. Weight within a BMI range of 19.0 - 30.0 kg/m2.
5. Estimated glomerular filtration rate (eGFR) according to the MDRD formula : \> 60 mL/min/1.73 m2.

Main Exclusion Criteria:

1. Unwilling or unable to give informed consent.
2. As a result of the medical screening process, the study physician considered the participant unfit for the study.
3. Male participants with female partners who are lactating or pregnant.
4. Known or suspected history of hypersensitivity to rifabutin or to drugs of a similar chemical class including rifampicin, rifapentine, rifaximin.
5. Known or suspected history of hypersensitivity to polymyxin B or colistin.
6. History of allergic reactions leading to hospitalization 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 participant and/or outcome of the study.
7. History of antibiotic associated diarrhoea within the last year.
8. Participants 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 \> 210 ms, or QRS duration \> 110 ms.
9. Supine systolic blood pressure \> 150 mmHg or \< 95 mmHg or diastolic blood pressure \> 95 mmHg or \< 45 mmHg at Screening or Period 1 Day 1 prior to dosing (any clinically relevant abnormal blood pressure results may be repeated once and if the repeat result is within the normal range, it is not considered to have met the exclusion criterion). Pulse rate \> 110 or \< 40 beats per minute at Screening or Period 1 Day 1 prior to dosing.
10. Clinically relevant abnormal values for leukocytes (total WBC), neutrophils, and lymphocytes (total), above the upper level of normal (ULN) or below the lower limit of normal (LLN) at screening, at the Investigator's discretion. Any clinically relevant abnormal value of these parameters may be repeated during screening.
11. Clinically relevant abnormal values for Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and creatinine, above the ULN at Screening, at the Investigator's discretion. Any clinically relevant abnormal value of these parameters may be repeated during screening.
12. Screening laboratory test values other than AST, ALT, ALP, creatinine, leucocytes, lymphocytes or neutrophils for haematology, biochemistry, or urinalysis must not exceed the reference range. Minor deviations from normal are allowed, if they are not considered clinically significant by the Investigator.

Where this trial is running

Vienna

• Medical University of Vienna — Vienna, Austria (Recruiting)

Conditions Healthy Adult Participants