To Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BAR502 in Healthy Subjects

Официальное название

A Phase I, Two Parts Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of BAR502 in Healthy Subjects

Обзор

First-in-human, single centre, two parts, dose-escalation, parallel-group, safety, tolerability, pharmacokinetic and pharmacodynamic Phase I study. Part A: randomised, double-blind, placebo-controlled, single ascending dose study. Part B: open label, multiple ascending dose study.

Подробное описание

First-in-human, single centre, two parts, dose-escalation, parallel-group, safety, tolerability, pharmacokinetic and pharmacodynamic Phase I study. Part A: randomised, double-blind, placebo-controlled, single ascending dose study to evaluate the safety and tolerability of BAR502 and matching placebo across 4 single ascending doses administered to 4 cohorts of 8 healthy subjects each.

Part B: open label, multiple ascending dose study to evaluate the safety and tolerability of two ascending doses of BAR502, considered as safe in study Part A, when administered as multiple doses to 2 cohorts of 10 healthy subjects each.

Вмешательства

• Препарат BAR502 single dose
  Single oral doses of BAR 502/placebo will be administered as film-coated tablets, in the morning of Day 1, with 150 mL of water, after an overnight fasting of at least 8 hours. BAR 502 film-coated tablets are available at dose strengths of 3, 10 and 50mg. A maximum of 4 dose levels are pre-planned (3, 10, 30 and 60mg).
• Препарат Placebo single dose
  Matching BAR 502 placebo film-coated tablets will be given to 2 out of 8 subjects in each cohort using the same regimen as outlined for the active study treatment
• Препарат BAR502 multiple doses
  The 2 multiple ascending doses selected based on results of study part A will be administered to 2 study cohorts of 10 subjects each. The IMP will be orally administered once a day from Day 1 to Day 14, at 8:00±1 h, for a total of 14 doses.

Первичные конечные точки

• Treatment-emergent adverse events [Срок оценки: PART A: Day-15/-2; Day-1 to Day4; Day 8; Day15 - PART B: Day-15/-2 to Day18; Day30]
• Change in vital sign - BP [Срок оценки: PART A: Day-1 to Day4; Day 8; - PART B: Day-15/-2 to Day15; Day18]
• Change in vital sign - HR [Срок оценки: PART A: Day-1 to Day4; Day 8; - PART B: Day-15/-2 to Day15; Day18]

Вторичные конечные точки (12)

• Plasma BAR502 - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3, Day4]
• Urine BAR502 - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3]
• Plasma BAR505 - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3, Day4]
• Urine BAR505 - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3]
• Plasma BAR502 PK: Cmax - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3, Day4]
• Plasma BAR502 PK: t_max - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3, Day4]
• Plasma BAR502 PK: AUC0-t - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3, Day4]
• Urine BAR502 PK: Ae0-t - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3]
• Urine BAR502 PK: Fe0-t - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3]
• Urine BAR502 PK: Rmax - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3]
• Urine BAR502 PK: AUR_Clast - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3]
• Urine BAR502 PK: REC% - Study Part A [Срок оценки: Day1 (pre- and post- dose), Day2, Day3]

Критерии участия

Критерии включения

• Informed consent: signed written informed consent before inclusion in the study
• Sex and Age: men/women, 18-55 years old inclusive
• Body Mass Index: 18.5-30 kg/m2 inclusive
• Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-99 bpm, measured after 5 min at rest in the sitting position
• Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study
• Renal functionality: estimated glomerular filtration rate calculated using the Cockcroft-Gault equation and normalized to an average surface area of 1.73 m2 ≥ 90 mL/min at screening
• Tobacco: non-smokers, non-users of nicotine containing products and non-users of Vapo e-cigarettes for at least 3 months prior to study screening
• Contraception and fertility (women only): women of non-child-bearing potential or in post-menopausal status for at least 1 year, defined as such when there is either:

• 12 months of spontaneous amenorrhea or
• 6 weeks documented postsurgical bilateral oophorectomy with or without hysterectomy will be admitted. For all women, pregnancy test result must be negative at screening and on Day -1 of each study part.
• Contraception (men only): men will either be sterile or agree to use one of the following approved methods of contraception from the first investigational medicinal product administration until at least 90 days after the last administration, also in case their partner is currently pregnant:

• A male condom with spermicide
• A sterile sexual partner or a partner in post-menopausal status for at least 1 year
• Use by the female sexual partner of an IUD, a female condom with spermicide, a contraceptive sponge with spermicide, a diaphragm with spermicide, a cervical cap with spermicide, or hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit or: True abstinence

Критерии исключения

• ECG 12-leads (supine position): clinically significant abnormalities, in particular QTcF > 450 ms
• Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
• Laboratory analyses: clinically significant abnormal laboratory values at screening indicative of physical illness or any acute laboratory abnormality at Screening which, in the opinion of the Investigator, should preclude participation in the study of an investigational compound. INR > 1.2
• Diseases: significant history of renal, hepatic (in particular, liver or hepatobiliary diseases as indicated by serum alanine aminotransferase, aspartate aminotransferase or total bilirubin levels exceeding the upper limit of normality), gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study
• Gallbladder: history of cholecystectomy, presence of gallstones or clinically significant gallbladder abnormalities that may interfere with the aim of the study
• Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study
• Medications: medications, including over the counter medications, homeopathic preparations, vitamins, food supplements and herbal remedies for 3 weeks before the start of the study
• Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
• Blood donation: blood donations for 3 months before this study
• Drug, alcohol, caffeine, tobacco: history of drug, alcohol \[>1 drink/day for females and >2 drinks/day for men, defined according to the USDA Dietary Guidelines 2020-2025\] or caffeine (>5 cups coffee/tea/day) abuse
• SARS-CoV-2 test: positive Covid-19 rapid test at Day -1
• Cotinine: positive cotinine test at screening
• Drug test: positive result at the urine drug screening test at screening or Day -1
• Alcohol test: positive alcohol saliva test at screening or Day -1
• Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians and vegans
• Pregnancy (women only): positive or missing pregnancy test at screening or Day -1; child-bearing potential, pregnant or lactating women.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Тройное слепое

Основная цель

Другое

Центры проведения

Швейцария · 1 центр

• CROSS Research S.A. Phase I Unit — Arzo

Идентификаторы

NCT: NCT06705998 · BAR-502-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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