Pharmacokinetics, Safety and Tolerability of ITF2357 in Participants With Chronic Hepatic Impairment and With Normal Hepatic Function

NCT06736223 | Completed Phase 1 FDA Drug

• 2 other identifiers: ITF/2357/602024-513577-43-00
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 3

Brief Summary

This is a multicentric, open-label, non-randomized study to evaluate the pharmacokinetic, safety and tolerability of ITF2357 in participants with chronic hepatic impairment relative to matched participants with normal hepatic function.

Conditions

Hepatic Impairment

Keywords

Hepatic impairment

Outcome Measures

Primary Outcomes (3)

• Maximum plasma concentration observed (Cmax) of ITF2357

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

• Area under the plasma concentration versus time curve to the real time tlast (AUClast) of ITF2357

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

• Area under the plasma concentration versus time curve extrapolated to infinity (AUC0-inf) of ITF2357

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

Secondary Outcomes (17)

• Time to reach Cmax (tmax) of ITF2357

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

• Apparent terminal half-life (t1/2) of ITF2357

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

• Apparent total plasma clearance from plasma (CL/F) of ITF2357

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

• Apparent volume of distribution (Vz/F) of ITF2357

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

• Maximum plasma concentration observed (Cmax) of ITF2357 metabolites

  Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

Study Arms (3)

Mild HI

EXPERIMENTAL

Patients with mild HI (Child-Pugh class A)

Drug: ITF2357

Moderate HI

EXPERIMENTAL

Patients with moderate HI (Child-Pugh class B)

Drug: ITF2357

Healthy Volunteers

EXPERIMENTAL

Participants with normal hepatic function (control group)

Drug: ITF2357

Interventions

ITF2357 DRUG

ITF2357 (INNM Givinostat hydrochloride Monohydrate), single dose

Also known as: Givinostat, Givinostat hydrochloride Monohydrate

Healthy Volunteers; Mild HI; Moderate HI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants, between 18 and 75 years of age, inclusive.
• Body weight between 60.0 and 110.0 kg, inclusive if male, and between 50.0 and 100.0 kg, inclusive if female, body mass index (BMI) between 18.00 and 34.99 kg/m2, inclusive.
• Stable chronic liver disease assessed by medical history, physical examination, laboratory values.
• Vital signs after 10 minutes resting in supine position within the following range \[or if out of range, considered not clinically significant (NCS) by the Investigator\]:
• mmHg \< systolic blood pressure (SBP) \< 180 mmHg 45 mmHg \< diastolic blood pressure (DBP) \< 100 mmHg 40 bpm \< heart rate (HR) \< 100 bpm. 5. 12-lead ECG without clinically significant abnormality, in the judgment of the Investigator; in no circumstances should participants be enrolled with corrected QT according to Fridericia (QTcF) \> 450 ms.
• \. Laboratory parameters within the acceptable range for participants with HI; however, serum creatinine should be strictly below the upper laboratory range.
• \. Female participants who are not pregnant or nursing at Screening and Day -1, or who are not planning to become pregnant during study period and until 4 weeks after the IMP administration.
• \. Female participants of non-childbearing potential, defined as one of the following:
• a. At least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., appropriate age) and follicle-stimulating hormone (FSH) in the range for menopausal female confirmed by blood test according to current local standards at screening.
• b. Those with history of hysterectomy or surgical removal of both ovaries or bilateral tubal ligation performed at least 90 days prior to Screening.
• \. Female participant of childbearing potential and male participant must agree to use an adequate and highly effective method of contraception (according to Clinical Trials Coordination Group \[CTCG\] recommendations) during the study and for at least 90 days after the study drug administration for women and for men. Such methods include:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation oral, intravaginal or transdermal.
• progestogen-only hormonal contraception associated with inhibition of ovulation oral, injectable or implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)

You may not qualify if:

• Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecological (if female), or infectious disease, or signs of acute illness.
• Hepatocarcinoma.
• Acute hepatitis.
• Hepatic encephalopathy grade 2, 3, and 4.
• Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in SBP ≥ 30 mmHg within 3 minutes when changing from supine to standing position.
• Presence or history of drug hypersensitivity, or allergic disease, except seasonal rhinitis, diagnosed and treated by a physician.
• Smoking more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 5 cigarettes per day from D-1 and throughout the entire institutionalization (i.e., up to D5).
• Excessive consumption of beverages with xanthine bases (more than 4 cups or glasses per day).
• If female, pregnancy \[defined as positive β-human choriogonadotropin (β-HCG) blood test\] or breast feeding.
• Consumption of PgP or BCRP potent inducers or inhibitors that could impact the PK of the investigational product.
• Any participant who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
• Any participant who cannot be contacted.
• Any participant who is the Investigator or any co-Investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study.
• Positive result on any of the following tests: anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
• Positive results on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates) unless this result is secondary to a documented medical prescription (only for benzodiazepines and cannabinoids).

Sponsors & Collaborators

• Italfarmaco: lead
• Biotrial: collaborator

Study Sites (3)

MC COMAC Medical Ltd

Sofia, 1606, Bulgaria

Location

MC COMAC Medical Ltd

Sofia, 1612, Bulgaria

Location

Biotrial

Rennes, 35042, France

Location

MeSH Terms

Interventions

givinostat hydrochloride; givinostat

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 16, 2024
• Study Start: May 28, 2025
• Primary Completion: August 13, 2025
• Study Completion: August 13, 2025
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

BU (2); FR (1)