Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BAR 502 in Healthy Subjects

NCT05203367 | Withdrawn Phase 1

• 1 other identifier: BLCL-BAR-502-101
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, randomized, double-blind, placebo-controlled, single-ascending dose (SAD) phase 1 study to evaluate the safety and tolerability of single-ascending doses of BAR 502 in healthy male and female subjects.

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

Non-alcoholic fatty liver disease; healthy; BAR 502

Outcome Measures

Primary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events

  Safety will be evaluated through the assessment of adverse events

  Through study completion, an average of 2 months

• Assessment of physical examination

  Safety will be evaluated through the assessment of physical examination, which will include: general appearance; skin; head and neck; thorax and abdomen; pulmonary auscultation; cardiac auscultation; abdomen palpation; limbs.

  At screening (Day -21 to Day -3 for male and female subjects of non-childbearing potential, Day -28 to Day -7 for female subjects of childbearing potential) and end of study ( Day 8)

• Assessment of 12-lead electrocardiogram

  Safety will be evaluated through the assessment of 12-lead ECG. The following variables are to be collected on the eCRF: HR (bpm), and the intervals PR (ms), QRS (ms), QT (ms), QTcB (ms) and QTcF (ms).

  At screening (Day -21 to Day -3 for male and female subjects of non-childbearing potential, Day -28 to Day -7 for female subjects of childbearing potential), admission (Day-1), and from day 1 to day 4 of the study

• Change from baseline at each time point of measurement in supine blood pressure (both systolic and diastolic)

  Safety will be evaluated through the assessment of vital signs (systolic and diastolic blood pressure)

  At screening (Day -21 to Day -3 for male and female subjects of non-childbearing potential, Day -28 to Day -7 for female subjects of childbearing potential), admission (Day -1), from Day 1 to Day 4 of the study, and at end of study (at Day 8).

• Change from baseline at each time point of measurement in pulse rate

  Safety will be evaluated through the assessment of vital signs

  At screening (Day -21 to Day -3 for male and female subjects of non-childbearing potential, Day -28 to Day -7 for female subjects of childbearing potential), admission (Day -1), from day 1 to day 4 of the study, and at end of study (at Day 8)..

Secondary Outcomes (15)

• Maximum concentration (Cmax)

  Within 1 hour prior to treatment administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 74 hours after treatment administration.

• Time of occurrence of Cmax (Tmax)

  Within 1 hour prior to treatment administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 74 hours after treatment administration.

• Area under the plasma concentration-time curve (AUC) from time zero to last sampling time with quantifiable concentrations (AUC0-t);

  Within 1 hour prior to treatment administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 74 hours after treatment administration.

• AUC extrapolated to infinity

  Within 1 hour prior to treatment administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 74 hours after treatment administration.

• Apparent terminal elimination rate constant (λz); and apparent terminal elimination half-life (t1/2)

  Within 1 hour prior to treatment administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 74 hours after treatment administration.

Study Arms (2)

BAR 502

EXPERIMENTAL

Each subject will receive an oral single-dose of BAR 502.

Drug: BAR502

Placebo

PLACEBO COMPARATOR

Each subject will receive an oral single-dose of placebo.

Drug: Placebo

Interventions

BAR502 DRUG

Single oral doses of BAR 502/placebo will be administered as film-coated tablets, in the morning of Day 1, with 240 mL of water, after an overnight fasting of at least 8 hours. BAR 502 film-coated tablets are available at dose strengths of 10, 50 and 150 mg. A maximum of 4 dose levels are pre-planned (10 mg, 50 mg, 150 mg, 300 mg).

BAR 502

Placebo DRUG

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

Placebo

Eligibility Criteria

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

You may qualify if:

• Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
• Ability to communicate well with the investigator, and to understand and comply with the study requirements.
• Healthy male or female subject aged between 18 and 55 years (inclusive) at Screening.
• Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at Screening.
• Systolic blood pressure (SBP) 90-140 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on same arm after ≥5 min in the seated position, at Screening.
• 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.
• If woman, she meets one of the following criteria:
• is of non-childbearing potential; or
• is of childbearing potential and agrees to use an accepted non-hormonal or hormonal contraceptive method.
• If man, he is infertile, vasectomized (i.e. who has received medical assessment of the surgical success) or agrees to abstain from or to use a condom during heterosexual intercourse with a woman of childbearing potential or a pregnant woman, and agrees not to donate sperm, from investigational product administration until at least 90 days after the investigational product administration. In addition, the subject must ensure that his female partner of childbearing potential agrees to consistently and correctly use one of the acceptable contraceptive methods mentioned above, for the same period of time.

You may not qualify if:

• \- At screening:
• Previous exposure to BAR 502.
• Known hypersensitivity to BAR 502, or any of its excipients.
• Clinically relevant findings on physical examination.
• Clinically relevant abnormalities on 12-lead ECG, measured after 5 min in a supine position.
• Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis).
• QTcF \> 450 ms in males and \> 470 ms in females.
• Medical history and/or clinical or laboratory evidence of liver or hepatobiliary disease or liver injury as indicated by serum alanine aminotransferase (ALT), AST, gamma-glutamyl transferase (GGT), ALP or total bilirubin levels exceeding the upper limit of normal (ULN).
• International Normalized Ratio (INR) \> 1.2.
• Any medical condition, acute, ongoing, recurrent or chronic, that presents a potential risk to the participant and/or that may compromise the objectives of the study.
• History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the distribution, metabolism, or excretion of the investigational product.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to Screening.
• Previous clinically relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
• Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture).
• Participation in a clinical study involving investigational product administration within 3 months prior to Screening or in more than 2 clinical studies within 1 year prior to Screening.

Sponsors & Collaborators

• BAR Pharmaceuticals s.r.l.: lead

Study Sites (1)

BlueClinical Phase I

Porto, Portugal

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

BAR502

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: A maximum of 4 BAR 502 dose levels are preplanned to be investigated in separate sequential cohorts. Each of these cohorts will consist of 8 healthy male and female subjects (3 subjects of either sex on active treatment, 1 of either sex on placebo). Each subject will participate in only one cohort.

Study Record Dates

• First Submitted: December 4, 2021
• First Posted: January 24, 2022
• Study Start: November 25, 2022
• Primary Completion: March 30, 2023
• Study Completion: March 30, 2023
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)