Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetics of BVL-GSK098 in Healthy Volunteers

NCT04654143 | Completed Phase 1 DMC

• 1 other identifier: BVL-GSK098
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I single-center, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics and food effect of BVL-GSK098 administered as single and multiple oral doses to healthy volunteers

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

  All AEs will be counted and described within each cohort/dose level, by treatment received and tabulated.

  From screening visit (Day -3 to -30) to end of study (7-10 days post last dose)

• Number of participants with clinically significant abnormal findings in hematology parameters

  Blood samples will be collected for the assessment of hematology parameters.

  Day 1 until end of study (7-10 days post last dose)

• Number of participants with clinically significant abnormal findings in clinical chemistry parameters

  Blood samples will be collected for the assessment of chemistry parameters.

  Day 1 until end of study (7-10 days post last dose)

• Number of participants with urinalysis findings

  Urine samples will be collected for the assessment of urinalysis parameters.

  Day 1 until end of study (7-10 days post last dose)

• Number of participants with clinically significant abnormal findings in vital signs

  Number of participants with abnormal vital signs will be assessed.

  Day 1 until end of study (7-10 days post last dose)

• Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters

  Triplicate 12-lead ECGs will be obtained

  Day 1 until end of study (7-10 days post last dose)

Secondary Outcomes (6)

• Maximum observed plasma drug concentration (Cmax) of BVL-GSK098

  Single dose: up to 72 hours; Multiple dose: up to 10 days

• Time to maximum observed plasma drug concentration (tmax) of BVL-GSK098

  Single dose: up to 72 hours; Multiple dose: up to 10 days

• Area under the plasma drug concentration versus time curve (AUC) of BVL-GSK098

  Single dose: up to 72 hours; Multiple dose: up to 10 days

• Apparent terminal half-life (t1/2) of BVL-GSK098 as appropriate

  Single dose: up to 72 hours; Multiple dose: up to 10 days

• The effect of food on the plasma concentrations of BVL-GSK098

  up to 72 hours

Study Arms (3)

Single Ascending Dose (SAD)

EXPERIMENTAL

There are multiple dose levels or cohorts. Each cohort has 6 subjects randomized to BVL-GSK098 and 2 subjects randomized to placebo.

Drug: BVL-GSK098 capsule, placebo

Multiple Ascending Dose (MAD)

EXPERIMENTAL

There are multiple dose levels or cohorts. Each cohort has 6 subjects randomized to BVL-GSK098 and 2 subjects randomized to placebo.

Drug: BVL-GSK098 capsule, placebo

Food Effect

EXPERIMENTAL

This cohort has 6 subjects randomized to BVL-GSK098 and 2 subjects randomized to placebo. Each participant will receive a single oral dose of BVL-GSK098 or placebo administered after the participant eats a high-fat, high calorie breakfast.

Drug: BVL-GSK098 capsule, placebo

Interventions

BVL-GSK098 capsule, placebo DRUG

Oral QD

Food Effect; Multiple Ascending Dose (MAD); Single Ascending Dose (SAD)

Eligibility Criteria

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

You may qualify if:

• Volunteers aged 18 to 55 years inclusive and between 19 and 30 kg/m2 body mass index (BMI) with a minimum weight of 50 kg or men and 45 kg for women, at the time of signing the informed consent.
• Volunteers who are healthy as determined by the investigator based on medical evaluation including medical history, physical examination and cardiac monitoring.
• Volunteers who have a clinically acceptable temperature, blood pressure and pulse rate in supine and standing position (systolic blood pressure between 100-140 mm Hg/ diastolic blood pressure between 50-90 mm Hg / HR between 50-100 bpm). Blood pressure and pulse will be measured after a minimum of 3 minutes of resting.
• Volunteers whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator.
• Male volunteers must use appropriate contraception (e.g. condoms as part of a double barrier method) from the time of the first dose until 3 months after the post-study visit.
• A female volunteer is eligible to participate if she is of non-childbearing potential, defined as:
• Is equal to or older than 45 years of age and has not had menses for greater than 1 year,
• Amenorrheic for less than 2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation,
• Whose status is post hysterectomy, oophorectomy or tubal ligation.
• Nonsmokers (i.e., one who has abstained from use of tobaccco and other nicotine-containing products for the last 6 months).
• Willingness to stay in the investigational site for up to 11 days.
• Volunteers are capable of giving signed informed consent which included compliance with the requirements and restrictions listed in the consent form and in this protocol.

You may not qualify if:

• Women of childbearing potential
• Pregnant or lactating women
• Men with female partners who are lactating or are pregnant
• Glomerular Filtration Rate (GFR) \< 90 mL/min/1.73m2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula.
• Alanine aminotransferase (ALT), Gamma glutamyl transferase (GGT), Aspartate aminotransferase (AST), alkaline phosphatase or serum bilirubin levels must not exceed the upper limit of normal (ULN)
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive test for HIV antibody.
• A positive pre-study drug/alcohol screen.
• Volunteers who consume more than 21 units of alcohol per week or who have a significant history of alcoholism or drug/chemical abuse (one unit of alcohol equals ½ pint \[285 mL\] of beer or lager, one glass \[125 mL\] of wine, or 30 mL of 40% of alcohol by volume distilled spirits).
• Volunteers who are study site employees, or immediate family members of a study site or sponsor employee.
• Volunteers 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), QTcB or QTcF \>450 ms or PR\>220 ms).
• Volunteers with a history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
• History of seizures.
• Volunteers who have received any prescribed systemic or topical medication within 4 weeks of the first dose administration.

Sponsors & Collaborators

• BioVersys AG: lead

Study Sites (2)

CIM Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Related Publications (1)

• Pieren M, Abaigar Gutierrez-Solana A, Antonijoan Arbos RM, Boyle GW, Davila M, Davy M, Gitzinger M, Husband L, Martinez-Martinez MS, Mazarro DO, Pefani E, Penman SL, Remuinan MJ, Vlasakakis G, Zeitlinger M, Dale GE. First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug. J Antimicrob Chemother. 2024 Jun 3;79(6):1353-1361. doi: 10.1093/jac/dkae107.

  PMID: 38656557 DERIVED

Study Officials

• Rosa M Antonijoan, MD

  Institut de Recerca de l'HSCSP. IIB Sant Pau.

  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 15, 2020
• First Posted: December 4, 2020
• Study Start: December 2, 2020
• 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

ES (2)