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

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

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.

Study Overview

• Status: Recruiting
• Conditions: NASH
• Intervention / Treatment: Drug: BAR502 single dose; Drug: Placebo single dose; Drug: BAR502 multiple doses

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Stefano Fiorucci, MD; Phone Number: +3905221403366; Email: stefano.fiorucci@unipg.it
• Study Contact Backup: Name: Fania Ferrari, BSc; Email: f.ferrari@barpharmaceuticals.com

Study Locations

• Switzerland
  • Arzo, Switzerland, CH-6864
    • Recruiting
    • CROSS Research S.A. Phase I Unit
    • Contact: Milko Radicione, MD; Phone Number: +41916404450; Email: milko.radicioni@croalliance.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Informed consent: signed written informed consent before inclusion in the study
2. Sex and Age: men/women, 18-55 years old inclusive
3. Body Mass Index: 18.5-30 kg/m2 inclusive
4. 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
5. 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
6. 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
7. 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

8. 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:

   1. 12 months of spontaneous amenorrhea or
   2. 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.

9. 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:

   1. A male condom with spermicide
   2. A sterile sexual partner or a partner in post-menopausal status for at least 1 year
   3. 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

Exclusion Criteria:

1. ECG 12-leads (supine position): clinically significant abnormalities, in particular QTcF > 450 ms
2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
3. 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
4. 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
5. Gallbladder: history of cholecystectomy, presence of gallstones or clinically significant gallbladder abnormalities that may interfere with the aim of the study
6. 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
7. Medications: medications, including over the counter medications, homeopathic preparations, vitamins, food supplements and herbal remedies for 3 weeks before the start of the study
8. 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
9. Blood donation: blood donations for 3 months before this study
10. 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
11. SARS-CoV-2 test: positive Covid-19 rapid test at Day -1
12. Cotinine: positive cotinine test at screening
13. Drug test: positive result at the urine drug screening test at screening or Day -1
14. Alcohol test: positive alcohol saliva test at screening or Day -1
15. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians and vegans
16. Pregnancy (women only): positive or missing pregnancy test at screening or Day -1; child-bearing potential, pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAR502 single dose; Each subject will receive an oral single-dose of BAR 502 [Study Part A]	Drug: 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).
Placebo Comparator: Placebo single dose; Each subject will receive an oral single-dose of placebo [Study Part A]	Drug: 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
Experimental: BAR502 multiple doses; Each subject will receive a dose of BAR502 once a day for 14 days [Study Part B]	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events	Safety will be evaluated through the assessment of adverse events	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	Tolerability will be evaluated throught the change in Blood preassure from baseline	PART A: Day-1 to Day4; Day 8; - PART B: Day-15/-2 to Day15; Day18
Change in vital sign - HR	Tolerability will be evaluated throught the change in Heart rate from baseline	PART A: Day-1 to Day4; Day 8; - PART B: Day-15/-2 to Day15; Day18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma BAR502 - Study Part A	Plasma BAR502 concentration-time profile after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3, Day4
Urine BAR502 - Study Part A	Urine BAR502 concentration-time profile after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Plasma BAR505 - Study Part A	Plasma BAR505 concentration-time profiles after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3, Day4
Urine BAR505 - Study Part A	Urine BAR505 concentration-time profiles after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Plasma BAR502 PK: Cmax - Study Part A	Plasma BAR502 Cmax value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3, Day4
Plasma BAR502 PK: t_max - Study Part A	Plasma BAR502 t_max value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3, Day4
Plasma BAR502 PK: AUC0-t - Study Part A	Plasma BAR502 AUC0-t value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3, Day4
Urine BAR502 PK: Ae0-t - Study Part A	Urine BAR502 Ae0-t value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Urine BAR502 PK: Fe0-t - Study Part A	Urine BAR502 Fe0-t value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Urine BAR502 PK: Rmax - Study Part A	Urine BAR502 Rmax value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Urine BAR502 PK: AUR_Clast - Study Part A	Urine BAR502 AUR_Clast value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Urine BAR502 PK: REC% - Study Part A	Urine BAR502 REC% value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Urine BAR502 PK: tu_max - Study Part A	Urine BAR502 tu_max value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Urine BAR502 PK: Cl_r r - Study Part A	Urine BAR502 Cl_r r value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum biomarker FGF19 - Study Part A	Serum FGF19 baseline-corrected concentration-time profile after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum biomarker C4 - Study Part A	Serum C4 baseline-corrected concentration-time profile and PD parameters after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum biomarker GLP-1 - Study Part A	Serum GLP-1 baseline-corrected concentration-time profile after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum PD: Cb_max - Study Part A	Serum Cb_max value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum PD: Cb_min - Study Part A	Serum Cb_min value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum PD: tb_max - Study Part A	Serum PD tb_max value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum PD: tb_min - Study Part A	Serum tb_min value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum PD: AUbC_0-24 - Study Part A	Serum AUbC_0-24 value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum PD: partial AUbC - Study Part A	Serum partial AUbC value after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Serum total bile acids - Study Part A	Serum total bile acids baseline-corrected concentration-time profiles after IMP single dose administration	Day1 (pre- and post- dose), Day2, Day3
Plasma BAR502 concentration - Study Part B	Plasma BAR502 concentration-time profile after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18
Plasma BAR505 concentration - Study Part B	Plasma BAR505 concentration-time profile after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18
Plasma BAR502 PK: Cmax - Study Part B	Plasma BAR502 Cmax value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18
Plasma BAR502 PK: t_max - Study Part B	Plasma BAR502 t_max value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18
Plasma BAR502 PK: AUC_0-24 - Study Part B	Plasma BAR502 AUC_0-24 value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18
Plasma BAR502 PK: AUC_0-t - Study Part B	Plasma BAR502 AUC_0-t value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day18
Serum biomarker GLP-1 - Study Part B	Serum GLP-1 baseline-corrected concentration-time profile after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum biomarker C4 - Study Part B	Serum C4 baseline-corrected concentration-time profile after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum biomarker FGF19 - Study Part B	Serum FGF19 baseline-corrected concentration-time profile after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum PD: Cb_max - Study Part B	Serum Cb_max value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum PD: Cb_min - Study Part B	Serum Cb_min value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum PD: tb_max - Study Part B	Serum tb_max value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum PD: tb_min - Study Part B	Serum tb_min after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum PD: AUbC_0-24 - Study Part B	Serum AUbC_0-24 value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum PD: partial AUbC - Study Part B	Serum partial AUbC value after IMP multiple dose	daily from Day1 to Day14 (pre- and post- dose); Day15 to Day17
Serum total bile acids - Study Part B	Serum total bile acids baseline-corrected concentration-time profiles after after IMP multiple dose	Daily from Day1 to Day17
Change in body weight	Change in body weight from baseline after single and multiple IMP dose	PART A: Day1; Day 8 - PART B: Day1; Day18; Day30
Check for Physical abnormalities	Change in Physical examination from baseline after single and multiple IMP dose	PART A: Day1; Day 8 - PART B: Day1; Day18; Day30
hepatic parameters: AST	Change from baseline in AST value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
hepatic parameters: ALT	Change from baseline in ALT value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
hepatic parameters: Total bilirubin	Change from baseline in Total bilirubin value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
hepatic parameters: Direct bilirubin	Change from baseline in Direct bilirubin value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
hepatic parameters: Indirect bilirubin	Change from baseline in Indirect bilirubin value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
hepatic parameters: Total cholesterol	Change from baseline in Total cholesterol value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
hepatic parameters: HDL cholesterol	Change from baseline in HDL cholesterol value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
hepatic parameters: LDL cholesterol	Change from baseline in LDL cholesterol value after single and multiple IMP dose	PART A: Day2; Day3; Day 8; - PART B: daily from Day2 to Day13; Day15; Day18
Change in Gallbladder contraction - Study Part B	Change from baseline in Gallbladder contraction after IMP multiple dose	daily from Day2 to Day13; Day15
Change in Gallbladder volume - Study Part B	Change from baseline in Gallbladder volume after IMP multiple dose	daily from Day2 to Day13; Day15
Change in ECG trace: PR	Change from baseline in ECG trace PR interval value after single and multiple IMP dose	PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15
Change in ECG trace: QRS	Change from baseline in ECG trace QRS interval value after single and multiple IMP dose	PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15
Change in ECG trace: QT	Change from baseline in ECG trace QT interval value after single and multiple IMP dose	PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15
Change in ECG trace: QTcB	Change from baseline in ECG trace QT interval corrected with Bazett's formula after single and multiple IMP dose	PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15
Change in ECG trace: QTcF	Change from baseline in ECG trace QT interval corrected with Fridericia's formula after single and multiple IMP dose	PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15
Change in ECG: Heart rate	Change from baseline in ECG Heart rate after single and multiple IMP dose	PART A: daily from Day1 to Day 4 - PART B: daily from Day to Day15

Collaborators and Investigators

• Sponsor: BAR Pharmaceuticals s.r.l.
• Investigators: Principal Investigator: Milko Radicioni, MD, CROSS Research S.A., Phase I Unit

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Non-alcoholic Fatty Liver DIsease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; BAR502
• Other Study ID Numbers: BAR-502-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No