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临床试验/NCT06705998
NCT06705998招募中1 期

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

BAR Pharmaceuticals s.r.l.1 个研究点 分布在 1 个国家目标入组 52 人开始时间: 2024年12月4日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
招募中
入组人数
52
试验地点
1
主要终点
Change in vital sign - BP
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Sequential
主要目的
Other
盲法
Triple (Participant, Investigator, Outcomes Assessor)

盲法说明

Double-blind: Active or placebo

入排标准

年龄范围
18 Years 至 55 Years（Adult）
性别
All
接受健康志愿者
是

入选标准

  • •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

排除标准

  • •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.

研究组 & 干预措施

BAR502 single dose

Experimental

Each subject will receive an oral single-dose of BAR 502 [Study Part A]

干预措施: BAR502 single dose (Drug)

Placebo single dose

Placebo Comparator

Each subject will receive an oral single-dose of placebo [Study Part A]

干预措施: Placebo single dose (Drug)

BAR502 multiple doses

Experimental

Each subject will receive a dose of BAR502 once a day for 14 days [Study Part B]

干预措施: BAR502 multiple doses (Drug)

结局指标

主要结局

Change in vital sign - BP

时间窗: PART A: Day-1 to Day4; Day 8; - PART B: Day-15/-2 to Day15; Day18

Tolerability will be evaluated throught the change in Blood preassure from baseline

Change in vital sign - HR

时间窗: PART A: Day-1 to Day4; Day 8; - PART B: Day-15/-2 to Day15; Day18

Tolerability will be evaluated throught the change in Heart rate from baseline

Treatment-emergent adverse events

时间窗: PART A: Day-15/-2; Day-1 to Day4; Day 8; Day15 - PART B: Day-15/-2 to Day18; Day30

Safety will be evaluated through the assessment of adverse events

次要结局

  • Serum biomarker C4 - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Serum biomarker GLP-1 - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Plasma BAR502 - Study Part A(Day1 (pre- and post- dose), Day2, Day3, Day4)
  • Urine BAR502 - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Plasma BAR505 - Study Part A(Day1 (pre- and post- dose), Day2, Day3, Day4)
  • Urine BAR505 - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Plasma BAR502 PK: Cmax - Study Part A(Day1 (pre- and post- dose), Day2, Day3, Day4)
  • Plasma BAR502 PK: t_max - Study Part A(Day1 (pre- and post- dose), Day2, Day3, Day4)
  • Plasma BAR502 PK: AUC0-t - Study Part A(Day1 (pre- and post- dose), Day2, Day3, Day4)
  • Urine BAR502 PK: Ae0-t - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Urine BAR502 PK: Fe0-t - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Urine BAR502 PK: Rmax - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Urine BAR502 PK: AUR_Clast - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Urine BAR502 PK: REC% - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Urine BAR502 PK: tu_max - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Urine BAR502 PK: Cl_r r - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Serum biomarker FGF19 - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Plasma BAR502 PK: AUC_0-t - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18)
  • Serum biomarker GLP-1 - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum PD: partial AUbC - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum PD: Cb_max - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Serum PD: partial AUbC - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Serum PD: Cb_min - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Serum PD: tb_min - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Serum total bile acids - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Plasma BAR502 concentration - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18)
  • Plasma BAR502 PK: AUC_0-24 - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18)
  • Serum biomarker C4 - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum biomarker FGF19 - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum PD: Cb_min - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum PD: tb_max - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Serum PD: AUbC_0-24 - Study Part A(Day1 (pre- and post- dose), Day2, Day3)
  • Plasma BAR505 concentration - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18)
  • Plasma BAR502 PK: Cmax - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18)
  • Plasma BAR502 PK: t_max - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18)
  • Serum PD: Cb_max - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum PD: tb_max - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum PD: tb_min - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Serum PD: AUbC_0-24 - Study Part B(daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17)
  • Change in ECG trace: QTcF(PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15)
  • Serum total bile acids - Study Part B(Daily from Day1 to Day17)
  • Change in body weight(PART A: Day1; Day 8 - PART B: Day1; Day18; Day30)
  • Check for Physical abnormalities(PART A: Day1; Day 8 - PART B: Day1; Day18; Day30)
  • hepatic parameters: AST(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • hepatic parameters: ALT(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • hepatic parameters: Total bilirubin(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • hepatic parameters: Direct bilirubin(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • hepatic parameters: Indirect bilirubin(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • hepatic parameters: Total cholesterol(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • hepatic parameters: HDL cholesterol(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • hepatic parameters: LDL cholesterol(PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18)
  • Change in Gallbladder contraction - Study Part B(daily from Day2 to Day13; Day15)
  • Change in Gallbladder volume - Study Part B(daily from Day2 to Day13; Day15)
  • Change in ECG trace: PR(PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15)
  • Change in ECG trace: QRS(PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15)
  • Change in ECG trace: QT(PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15)
  • Change in ECG trace: QTcB(PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15)
  • Change in ECG: Heart rate(PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15)

研究者

申办方类型
Network
责任方
Sponsor

研究点 (1)

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