A Study to Assess Effect of BV100 on the Pharmacokinetics of Midazolam in Healthy Participants

NCT05537090 | Completed Phase 1

• 1 other identifier: BV100-005
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the effect of repeated doses of intravenous BV100 on the pharma-cokinetics of midazolam and 1-hydroxymidazolam.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• To evaluate the effect of repeated doses of intravenous BV100 on the pharmacokinetics of midazolam

  Maximum Observed Plasma Concentration (Cmax) of Midazolam

  0 (predose) up to 24 hours postdose on Day 1 and Day 7

• To evaluate the effect of repeated doses of intravenous BV100 on the pharmacokinetics of midazolam

  Area Under the Plasma Concentration-Time Curve (AUC) of Midazolam

  0 (predose) up to 24 hours postdose on Day 1 and Day 7

• To evaluate the effect of repeated doses of intravenous BV100 on the pharmacokinetics of 1-hydroxymidazolam

  Maximum Observed Plasma Concentration (Cmax) of 1-hydroxymidazolam

  0 (predose) up to 24 hours postdose on Day 1 and Day 7

• To evaluate the effect of repeated doses of intravenous BV100 on the pharmacokinetics of 1-hydroxymidazolam

  Area Under the Plasma Concentration-Time Curve (AUC) of 1-hydroxymidazolam

  0 (predose) up to 24 hours postdose on Day 1 and Day 7

Secondary Outcomes (1)

• To evaluate the safety, and tolerability in healthy volunteers receiving multiple intravenous doses of BV100 with and without midazolam

  26 days

Study Arms (1)

BV100 Plus Midazolam

EXPERIMENTAL

A total 2 doses of midazolam and 9 doses of BV100 will be administered to each participant per specified dosing schedule

Drug: BV100; Drug: Midazolam

Interventions

BV100 DRUG

Rifabutin for Infusion

BV100 Plus Midazolam

Midazolam DRUG

Syrup for oral administration

BV100 Plus Midazolam

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who were able to understand and follow instructions during the study.
• Subjects who signed informed consent.
• Male subjects ≥18 and ≤55 years of age; female subjects ≥18 and ≤55 years of age of nonchildbearing 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 19.0-30.0 kg/m2.
• Estimated glomerular filtration rate (eGFR) according to the CKD-EPI: ≥90 mL/min (normal renal function)
• Healthy subjects had to be in a good health in the opinion of the study phy-sician, as determined by medical history, ECG, vital signs, physical examina-tion, and clinical laboratory tests.
• Having had no febrile or infectious illness for at least 14 days prior to dos-ing.
• The subject was available to complete the study.
• The subject was complying with the restrictions and requirements of the protocol and, in the opinion of the study physician, was able to complete the study.

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 outcome of the study.
• History of antibiotic associated diarrhoea within the last year.
• Volunteers with ECG abnormalities (history, or evidence of second-degree heart block of Mobitz type II, third degree heart block, or any abnormality con-sidered relevant by the Investigator), QTcF \> 450 ms, PR \> 200 ms, or QRS duration \> 110 ms.
• Supine systolic blood pressure \> 140 mmHg or \< 90 mmHg or diastolic blood pressure \> 90 mmHg or \< 50 mmHg at Screening or Day 1 prior to dos-ing (any abnormal blood pressure results may be repeated once and if the re-peat result is within the normal range, it is not considered to have met the ex-clusion criterion). Pulse rate \> 90 or \< 50 beats per minute at Screening or Day 1 prior to dosing.
• Screening values other than AST, ALT, ALP, creatinine, for haematology, biochemistry, or urinalysis must not exceed the reference range. Minor devia-tions from normal are allowed, if they are not clinically significant.
• Leucocytes or neutrophils or lymphocytes below the lower limit of the ref-erence range.
• History of symptomatic, chronic or recurrent infection (e.g. nausea, vomit-ing, 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 clini-cal unit.
• \. A positive pre-study serology test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV)-1 and/or 2 antibodies.
• \. Positive Coronavirus (SARS-CoV-2) rapid test and PCR (upon Check-in on Day -1) 14. A positive pre-study drug/alcohol screen. 15. History of epilepsy, other neurological disorders, or neuropsychiatric con-ditions.
• \. History of seizures. 17. Volunteers who have received any prescribed systemic or topical medica-tion within 4 weeks of the first dose administration.
• \. Subjects who had used any non-prescribed systemic or topical medication (including herbal remedies) or megadose vitamins (i.e. 20 to 600 times the rec-ommended daily supplement dose) within 7 days prior to dosing, unless in the opinion of the study physician the medication did 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 within 30 days of the first dose administration.

Sponsors & Collaborators

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

Study Sites (1)

CRU Hungary Kft., Early Phase Unit

Kistarcsa, H-2143, Hungary

Location

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Geza Lakner

  Clinical Research Units Hungary

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is an open-label, 3 period fixed-sequence, Phase 1 clinical study to evalu-ate the effect of multiple doses of BV100 on the Pharmacokinetics on midazo-lam and its metabolite 1-hydroxymidazolam in healthy volunteers.

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 13, 2022
• Study Start: September 1, 2022
• Primary Completion: July 31, 2023
• Study Completion: September 30, 2023
• Last Updated: November 21, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)