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

Phase 1

Not yet recruiting

• Conditions: Hepatic Impairment
• Interventions: Drug: ITF2357

• Registration Number: NCT06736223
• Lead Sponsor: Italfarmaco

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.

Detailed Description

This study will evaluate the effect of mild and moderate hepatic impairment (HI) on the pharmacokinetics of ITF2357 and its metabolites.

The total number of participants to be enrolled in the study is 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 will go 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 Timeline

• Study First Submitted: 2024-12-06
• Study First Submitted QC: 2024-12-12
• Study First Posted: 2024-12-16
• Status Verified: 2025-05
• Study Start: 2025-05
• Last Update Submitted: 2025-05-15
• Last Update Posted: 2025-05-16
• Primary Completion: 2025-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Healthy Volunteers	ITF2357	Participants with normal hepatic function (control group)
Mild HI	ITF2357	Patients with mild HI (Child-Pugh class A)
Moderate HI	ITF2357	Patients with moderate HI (Child-Pugh class B)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Area under the plasma concentration versus time curve to the real time tlast (AUClast) of ITF2357 metabolites	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 metabolites	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Time to reach Cmax (tmax) of ITF2357 metabolites	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Apparent terminal half-life (t1/2) of ITF2357 metabolites	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Unbound fraction (fu) of ITF2357 and its metabolites	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Unbound area under the plasma concentration time curve (AUCu) of ITF2357 and its metabolites	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Unbound maximum plasma concentration observed (Cmax,u) of ITF2357 and its metabolites	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Unbound apparent total plasma clearance (CL/Fu) of ITF2357	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Unbound apparent volume of distribution (Vz/Fu) of ITF2357	Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Electrocardiogram QT interval corrected according to Fredericia's formula (ECG QTcF)	From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)
Incidence of Treatment Emergent Adverse Events (TEAEs)	From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)	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
Severity of Treatment Emergent Adverse Events (TEAEs)	From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)	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

Trial Locations

Locations (2)

MC COMAC Medical Ltd; 🇧🇬 Sofia, Bulgaria

Biotrial; 🇫🇷 Rennes, France