Hepatic ImpairmentPhase 1NCT06736223
Pharmacokinetics, Safety and Tolerability of ITF2357 in Participants With Chronic Hepatic Impairment and With Normal Hepatic Function
A Phase 1 study testing ITF2357 in people with Hepatic Impairment, run by Italfarmaco at 3 sites in 2 countries.
Trial summary
This was 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- ITF2357
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 29 May 2025to 14 Aug 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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]: 95 mmHg < systolic blood pressure (SBP) < 180 mmHg; 45 mmHg < diastolic blood pressure (DBP) < 100 mmHg; 40 bpm < heart rate (HR) < 100 bpm.
- 12-lead ECG without clinically significant abnormality, in the judgment of the Investigator; in no circumstances were participants enrolled with corrected QT according to Fridericia (QTcF) > 450 ms.
- Any confirmed clinically relevant abnormal laboratory test that, on Investigator's judgment, was inconsistent with the subject's status as a patient with hepatic impairment. However, renal function assessed using the estimated glomerular filtration rate (eGFR) calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula had to be strictly above 60 mL/min/1.73m².
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- Female participants who were not pregnant or nursing at screening and D-1, or who were not planning to become pregnant during study period and until 90 days after the IMP administration.
- Female participants of non-childbearing potential, defined as one of the following:
- 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;
- 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 (if sexually active with a woman of childbearing potential and not sterile) and his partner had to 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);
- bilateral tubal occlusion;
- vasectomized partner;
- sexual abstinence (when in line with the preferred and usual subject's lifestyle).
- Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception.
- Had given written informed consent prior to any procedure related to the study.
- Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.
- Not under any administrative or legal supervision.
- For moderate HI cohort: Child-Pugh total score ranging from 7 to 9, inclusive.
- For mild HI cohort: Child-Pugh total score ranging from 5 to 6, inclusive.
- Male participants had to agree not to donate sperm from inclusion up to 3 months after ITF2357 dosing.
Who cannot join
- 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.
- Blood donation within 2 months before inclusion.
- 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 changed from supine to standing position.
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- Presence or history of drug hypersensitivity, or allergic disease, except seasonal rhinitis, diagnosed and treated by a physician.
- History or presence of regular use of recreational drugs or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis) within 2 years before inclusion.
- 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.
- Any significant change in chronic treatment medication within 14 days before inclusion.
- Consumption of PgP or BCRP potent inducers or inhibitors that could impact the PK of the investigational product within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic (PD) half-life of the medication before inclusion.
- Note: If any of those drugs was planned to be administered in any of the potential participants, it was postponed for at least until the EOS visit is completed.
- Any vaccination, including COVID-19 within 2 weeks before inclusion.
- Any participant who, in the judgment of the Investigator, was likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
- Any participant in the exclusion period of a previous study according to applicable regulations.
- Any participant who could not be contacted.
- Any participant who was 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 was secondary to a documented medical prescription (only for benzodiazepines and cannabinoids).
- Positive alcohol breath test.
- Any consumption of citrus fruits (grapefruit, Seville orange, etc.) or their juices within 5 days before inclusion.
- Medications that prolong the QTc interval (refer to the list provided in Section 12 of Appendix 16.1.1) within 14 days before inclusion or within 7 times the elimination half-life before inclusion.
- Note: If any of those drugs was planned to be administered in any of the potential participants, it was postponed for at least until the last ECG at EOS is completed.
- Had a risk factor of QT prolongation (as for example electrolyte imbalances) or a personal or a family history of prolonged QT interval syndrome or torsade de pointes, or family history of sudden death.
- Inclusion Criteria for Participants with normal hepatic function:
- Male or female participants, between 18 and 75 years of age, inclusive.
- Body weight within 10% of the mean body weight of the participants with moderate HI, and BMI between 18.00 and 34.99 kg/m2, inclusive.
- Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
- Vital signs after 10 minutes resting in the supine position within the following range (or if out of range, considered NCS by the Investigator): 95 mmHg < SBP < 140 mmHg; 45 mmHg < DBP < 90 mmHg; 40 bpm < HR < 100 bpm.
- 12-lead ECG without clinically significant abnormality, in the judgment of the Investigator; in no circumstances participants could have been enrolled with QTcF > 450 ms.
- Laboratory parameters within the normal range, unless the Investigator considered an abnormality to be clinically irrelevant for healthy participants, except in the case of platelets, white blood cells and hemoglobin below lower limit of normal (LLN). However serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase), total bilirubin (unless the participant has documented Gilbert's syndrome, with a maximum bilirubin level lower than 3 x upper limit of normal (ULN), and any parameter for which there was an explicit stopping rule could not exceed the upper laboratory range; renal function assessed using the eGFR calculated by the 2021 CKD-EPI formula had to be strictly above 60 mL/min/1.73m².
- Female participants who were not pregnant or nursing at screening and D-1, or who were not planning to become pregnant during study period and until 90 days after the IMP administration.
- Female participants of non-childbearing potential, defined as one of the following:
- At least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. appropriate age) and FSH in the range for menopausal female confirmed by blood test according to current local standards at screening.
- 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 (if sexually active with a woman of childbearing potential and not sterile) and his partner had to agree to use an adequate and highly effective method of contraception (according to 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);
- bilateral tubal occlusion;
- vasectomized partner;
- sexual abstinence (when in line with the preferred and usual subject's lifestyle).
- Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and LAM were not acceptable methods of contraception.
- Had given written informed consent prior to any procedure related to the study.
- Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.
- Not under any administrative or legal supervision.
- Male participants had to agree not to donate sperm from inclusion up to 3 months after ITF2357 dosing.
- Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecological (if female), or infectious disease, or signs of acute illness.
- Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
- Blood donation within 2 months before inclusion.
- Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in SBP ≥ 20 mmHg within 3 minutes when changed from supine to standing position.
- Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician, except seasonal rhinitis.
- History or presence of regular use of recreational drugs or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis) within 2 years before inclusion.
- Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking from D-1 and throughout the entire institutionalization (i.e. up to D5).
- Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day).
- If female, in a status of pregnancy (defined as positive β-HCG blood test), or breast-feeding.
- Any medication (including PgP or BCRP inducers or inhibitors, or omeprazole) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic (PD) half-life of the medication (except HRT and contraception when applicable), any vaccination within the last 28 days (except COVID-19 vaccination) and any biologics (antibody or its derivatives) given within 4 months before inclusion.
- Any vaccination, including COVID-19 within 2 weeks before inclusion.
- Any participant who, in the judgment of the Investigator, was likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
- Any participant in the exclusion period of a previous study according to applicable regulations.
- Any participant who could not be contacted.
- Any participant who was 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: hepatitis B surface antigen (HBs Ag), anti-hepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, anti-HIV1 and anti-HIV2 Ab.
- Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
- Positive alcohol breath test.
- Any consumption of citrus (grapefruit, Seville orange, etc.) or their juices within 5 days before inclusion.
- Had a risk factor of QT prolongation (as for example electrolyte imbalances) or a personal or a family history of prolonged QT interval syndrome or torsade de pointes, or family history of sudden death.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Bulgaria2 sites
MC COMAC Medical Ltd
Sofia, 1606
MC COMAC Medical Ltd
Sofia, 1612
About this study
Official title: A Multicentric, Open-label, Non-randomized Study to Evaluate the Pharmacokinetic, Safety and Tolerability of ITF2357 Given as an Oral Single 50 mg Dose in Participants With Chronic Hepatic Impairment Relative to Matched Participants With Normal Hepatic Function
This was 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.
Read the detailed description
This study evaluated the effect of mild and moderate hepatic impairment (HI) on the pharmacokinetics of ITF2357 and its metabolites, along with the safety and tolerability in this patient population.
The total number of participants enrolled in the study was 24 subjects:
- 8 participants with mild HI (Child-Pugh class A)
- 8 participants with moderate HI (Child-Pugh class B)
- 8 participants with normal hepatic function (control group)
Each participant went through:
- A screening period from Day (D)-28 to D-2
- One 6-day/5-night inpatient period (from D-1 evening to D5 morning)
- An end-of-study evaluation to be done on D10 (±1 day).
- Conditions
- Hepatic Impairment
- Being tested
- ITF2357
- Keywords
- Hepatic impairment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ITF2357Drug
Also called Givinostat, Givinostat hydrochloride monohydrate
ITF2357 (INNM Givinostat hydrochloride monohydrate), single dose
| Study group | Role | What they receive |
|---|---|---|
| Mild HI | Experimental | Patients with mild HI (Child-Pugh class A) Receives: Drug: ITF2357 |
| Moderate HI | Experimental | Patients with moderate HI (Child-Pugh class B) Receives: Drug: ITF2357 |
| Healthy Volunteers | Experimental | Participants with normal hepatic function (control group) Receives: Drug: ITF2357 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of ITF2357
Maximum plasma concentration observed
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUClast of ITF2357
Area under the plasma concentration versus time curve to the real time tlast
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUC0-inf of ITF2357
Area under the plasma concentration versus time curve extrapolated to infinity
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Secondary outcomes (24)
Tmax of ITF2357
Time to reach Cmax
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
t1/2 of ITF2357
Apparent terminal half-life
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
CL/F of ITF2357
Apparent total plasma clearance from plasma
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Vz/F of ITF2357
Apparent volume of distribution
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Cmax of ITF2357 Metabolites
Maximum plasma concentration observed
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUClast of ITF2357 Metabolites
Area under the plasma concentration versus time curve to the real time tlast
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUC0-inf of ITF2357 Metabolites
Area under the plasma concentration versus time curve extrapolated to infinity
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Tmax of ITF2357 Metabolites
Time to reach Cmax
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
t1/2 of ITF2357 Metabolites
Apparent terminal half-life
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Fu of ITF2357 and Its Metabolites
Unbound fraction (fu) is the fraction of total plasma drug concentration that is not bound to plasma proteins and is pharmacologically available
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUC0-last,u of ITF2357 and Its Metabolites
Unbound area under the plasma concentration versus time curve to the real time Tlast
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUC0-inf,u of ITF2357 and Its Metabolites
Unbound area under the plasma concentration versus time extrapolated to infinity
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Cmax,u of ITF2357 and Its Metabolites
Unbound maximum plasma concentration observed
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
CL/Fu of ITF2357
Unbound apparent total plasma clearance
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Vz/Fu of ITF2357
Unbound apparent volume of distribution
Measured: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Incidence of Treatment Emergent Adverse Events (TEAEs)
Number of participants with at least one related TEAEs. Treatment Emergent Adverse Event is defined as any untoward medical occurrence (including an abnormal laboratory finding, symptom or a disease) in a participant administered the pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment.
Measured: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Treatment-Related TEAEs
Number of participants with at least one related TEAEs
Measured: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Severity of Treatment Emergent Adverse Events (TEAEs)
Number of participants with at least one TEAEs according to NCI-CTCAE grade version 5.0, where severity is classified as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), and Grade 5 (death related to the adverse event).
Measured: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of TEAEs Leading to Withdrawal From the Study
Number of participants with at least one TEAE leading to withdrawal from the study
Measured: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Serious TEAEs (SAEs)
Number of participants with at least one Serious TEAE
Measured: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Clinical Laboratory Parameters Abnormality
Number of participants with at least one clinically significant laboratory parameters abnormality. The following parameters were measured: Hematology: Hemoglobin, hematocrit, erythrocytes, platelets, leukocytes, and differential counts (basophils, eosinophils, lymphocytes, monocytes, neutrophils). Blood chemistry: Sodium, potassium, chloride, calcium, urea, creatinine, albumin, glucose, total proteins, triglycerides, total cholesterol, ALT, AST, GGT, CPK, alkaline phosphatase, total bilirubin. Coagulation: PT, INR, aPTT. Serology: HBsAg, anti-HBc, anti-HCV, anti-HIV-1/2, pregnancy test (hCG). Urinalysis: pH, protein, glucose, leukocytes, nitrites, ketones, blood. Other: Alcohol breath test; urine drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
Measured: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Vital Signs Abnormality
Number of participants with at least one clinically significant vitals abnormality. The following clinical signs were measured: body temperature (C°), supine systolic blood pressure (mmHg), diastolic blood pressure (mmHg), pulse rate (beats/min), and respiratory rate (breath/min).
Measured: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Electrocardiogram Abnormality
Number of participants with at least one clinically significant electrocardiogram abnormality. The following standard 12-lead ECG were recorded: heart rate (beats/min), PR interval (msec), QRS duration (msec), QRS axis (deg), QT interval (msec) and Fridericia and Bazett QTc interval (msec)
Measured: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Physical Examination Abnormality
Number of participants with at least one clinically significant physical abnormality. A complete physical examination, including at a minimum assessments of the cardiovascular, respiratory, gastrointestinal, dermatological, neurological, and musculoskeletal systems, in addition to examinations of the head, eyes, ears, nose, throat, neck, and lymph nodes, as well as height and weight measurement.
Measured: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2024
- Study start29 May 2025
- Primary completion14 Aug 2025
- Study completion14 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italfarmaco
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biotrial
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06736223
- Sponsor's protocol ID
- ITF/2357/60
- Other IDs
- 2024-513577-43-00
- Status last verified
- May 2026
- First submitted
- 6 Dec 2024
- Last updated
- 18 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentric, Open-label, Non-randomized Study to Evaluate the Pharmacokinetic, Safety and Tolerability of ITF2357 Given as an Oral Single 50 mg Dose in Participants With Chronic Hepatic Impairment Relative to Matched Participants With Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT06736223
- Acronym / sponsor ID
- ITF/2357/60
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- ItalfarmacoIndustry (pharma, biotech, devices)
- Collaborators
- Biotrial
- Study start
- 29 May 2025 (actual)
- Primary completion
- 14 Aug 2025 (actual)
- Study completion
- 14 Aug 2025 (actual)
- First posted
- 16 Dec 2024 (actual)
- Results
- Posted 18 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was 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.
Detailed description
This study evaluated the effect of mild and moderate hepatic impairment (HI) on the pharmacokinetics of ITF2357 and its metabolites, along with the safety and tolerability in this patient population.
The total number of participants enrolled in the study was 24 subjects:
- 8 participants with mild HI (Child-Pugh class A)
- 8 participants with moderate HI (Child-Pugh class B)
- 8 participants with normal hepatic function (control group)
Each participant went through:
- A screening period from Day (D)-28 to D-2
- One 6-day/5-night inpatient period (from D-1 evening to D5 morning)
- An end-of-study evaluation to be done on D10 (±1 day).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mild HI | Experimental | Drug: ITF2357Patients with mild HI (Child-Pugh class A) |
| Moderate HI | Experimental | Drug: ITF2357Patients with moderate HI (Child-Pugh class B) |
| Healthy Volunteers | Experimental | Drug: ITF2357Participants with normal hepatic function (control group) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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]: 95 mmHg < systolic blood pressure (SBP) < 180 mmHg; 45 mmHg < diastolic blood pressure (DBP) < 100 mmHg; 40 bpm < heart rate (HR) < 100 bpm.
- 12-lead ECG without clinically significant abnormality, in the judgment of the Investigator; in no circumstances were participants enrolled with corrected QT according to Fridericia (QTcF) > 450 ms.
Key exclusion criteria (70 listed)
- 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.
- Blood donation within 2 months before inclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ITF2357Also: Givinostat, Givinostat hydrochloride monohydrateITF2357 (INNM Givinostat hydrochloride monohydrate), single dose | Drug | Healthy Volunteers, Mild HI, Moderate HI |
Primary outcome
Cmax of ITF2357
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Maximum plasma concentration observed
AUClast of ITF2357
Time frame: 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
AUC0-inf of ITF2357
Time frame: 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
24 secondary outcomes
Tmax of ITF2357
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
t1/2 of ITF2357
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
CL/F of ITF2357
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Vz/F of ITF2357
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Cmax of ITF2357 Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUClast of ITF2357 Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUC0-inf of ITF2357 Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Tmax of ITF2357 Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
t1/2 of ITF2357 Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Fu of ITF2357 and Its Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUC0-last,u of ITF2357 and Its Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
AUC0-inf,u of ITF2357 and Its Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Cmax,u of ITF2357 and Its Metabolites
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
CL/Fu of ITF2357
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Vz/Fu of ITF2357
Time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time frame: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Treatment-Related TEAEs
Time frame: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Severity of Treatment Emergent Adverse Events (TEAEs)
Time frame: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of TEAEs Leading to Withdrawal From the Study
Time frame: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Serious TEAEs (SAEs)
Time frame: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Clinical Laboratory Parameters Abnormality
Time frame: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Vital Signs Abnormality
Time frame: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Electrocardiogram Abnormality
Time frame: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Clinically Significant Physical Examination Abnormality
Time frame: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ITF2357 in people with Hepatic Impairment, run by Italfarmaco at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 70 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Bulgaria, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax of ITF2357 (time frame: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.