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NCT05860114

Givinostat and Metabolites Pharmacokinetics in Urine and Plasma (Part 3)

Completed Phase 1 Results posted Last updated 24 January 2025
What this trial tests

Phase 1 trial testing Givinostat in Drug Drug Interaction in 8 participants. Completed in 24 May 2022.

Timeline
21 March 2022
Primary endpoint
8 May 2022
24 May 2022

Quick facts

Lead sponsorItalfarmaco
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment8
Start date21 March 2022
Primary completion8 May 2022
Estimated completion24 May 2022
Sites1 location across Portugal

Drugs / interventions tested

Conditions studied

Sponsor

Italfarmaco — full company profile →

Who can join

Adults 18 to 55, any sex, with Drug Drug Interaction. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Plasma Pharmacokinetic (PK) Parameters of Givinostat, Following First Single-dose Administration of Givinostat: Cmax Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1.

Cmax is the Maximum Observed Plasma Concentration. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). A total of 22 blood samples were collected as follows: \- 22 blood samples at pre-dose and at the timepoints indicated in the timeframe field after the administration of Givinostat (post-dose), on Days 1, for the determination of Givinostat and its metabolites plasma concentrations using a validated LC-MS/MS analytical method. Summary Statistics for the main PK parameters, like Cmax, Following Single-Dose Administration of Givinostat (Day 1)

GroupValue95% CI
Givinostat48.06± 25.8
ITF23747.34± 45.7
ITF2375132.20± 40.2
ITF244088.77± 16.4
ITF256315.38± 13.8
Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: Tmax Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1.

Tmax is the Time to Maximum Observed Concentration.The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). A total of 22 blood samples were collected as follows: \- 22 blood samples at predose and at the timepoints indicated in the timeframe field after the administration of Givinostat (post-dose), on Days 1, for the determination of Givinostat and its metabolites plasma concentrations. Summary Statistics for the main PK parameters, like tmax, Following Single-Dose Administration of Givinostat (Day 1) are reported.

GroupValue95% CI
Givinostat1.501.00 – 3.50
ITF23745.505.00 – 12.00
ITF23753.502.00 – 4.00
ITF24409.008.00 – 12.00
ITF256310.008.00 – 12.00
Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-Dose Administration of Givinostat: Ctrough Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1 and on Day 13.

Ctrough is the Pre-dose Plasma Concentration. On Day 1 and Day 13, Givinostat 50 mg as oral suspension was administered as a single dose, in the morning, following an overnight fasting of at least 8 hours and subjects remained fasted until at least 4 hours post-dose. From Day 5 to Day 12 Givinostat 50 mg as oral suspension was administered twice daily. A total of 48 blood samples were collected: * 22 during single-dose treatment (Day 1, at pre-dose and at the timepoints indicated in the timeframe post-dose) and * 26 during the multiple dose treatment (Days 5-12 plus single-dose treatment at

single dose (Day 1)
GroupValue95% CI
Givinostat6.75± 22.3
ITF23744.14± 42.6
ITF237528.47± 53.3
ITF244081.58± 14.9
ITF256314.75± 11.1
multiple dose (Day 13)
GroupValue95% CI
Givinostat13.16± 28.7
ITF237410.18± 50.8
ITF237556.12± 60.6
ITF2440279.96± 15.6
ITF256350.11± 18.8
Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: AUC0-inf. Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1 and on Day 13.

AUC0-inf is the AUC from Time Zero to Infinity. On Day 1 and Day 13, givinostat 50 mg as oral suspension was administered as a single dose, in the morning, following an overnight fasting of at least 8 hours and subjects remained fasted until at least 4 hours post-dose. From Day 5 to Day 12 givinostat 50 mg as oral suspension was administered twice daily. A total of 48 blood samples were collected: * 22 during single-dose treatment (Day 1, at pre-dose and at the timepoints indicated in the timeframe post-dose) and * 26 during the multiple dose treatment (Days 5-12 plus single-dose treatment a

Single-dose (Day 1)
GroupValue95% CI
Givinostat305.72± 21.0
ITF237499.01± 49.1
ITF23751239.34± 47.8
ITF24402431.31± 12.1
ITF2563457.95± 13.4
Multiple-dose (Day 13)
GroupValue95% CI
Givinostat562.42± 17.5
ITF2374337.71± 53.2
ITF23752754.89± 77.8
ITF24409526.56± 30.2
ITF25631715.62± 23.0
Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: AUC0-t. Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1 and on Day 13.

AUC0-t is the AUC from Time Zero to Last Sampling Time with Quantifiable. On Days 1 and 13, Givinostat 50 mg as oral suspension was administered as a single dose, in the morning, following an overnight fasting of at least 8 h and subjects remained fasted until at least 4 h post-dose. From Day 5 to Day 12 Givinostat 50 mg as oral suspension was administered twice daily. 48 blood samples were collected in total: * 22 during single-dose treatment (Day 1, at pre-dose and at the timepoints indicated in the timeframe post-dose), * 26 during the multiple dose treatment (Days 5-12 plus single-dose t

Single-dose (Day 1)
GroupValue95% CI
Givinostat300.45± 21.3
ITF237493.30± 51.0
ITF23751223.60± 47.5
ITF24402345.60± 12.7
ITF2563439.59± 13.0
Multiple-dose (Day 13)
GroupValue95% CI
Givinostat554.78± 17.5
ITF2374328.36± 53.9
ITF23752609.03± 68.2
ITF24409262.28± 27.4
ITF25631681.26± 21.8
Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: AUC0-τ Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1.

AUC0-τ is the area under the plasma concentration versus time curve. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). A total of 22 blood samples were collected as follows: \- 22 blood samples at pre-dose and at the timepoints indicated in the timeframe field after the administration of Givinostat (post-dose), on Days 1, for the determination of Givinostat and its metabolites plasma concentrations. Summary Statistics for the main PK parameters, like AUC0-τ, Following Single-Dose Administration of Givinostat (Day 1) are reported.

GroupValue95% CI
Givinostat245.73± 23.2
ITF237452.48± 42.2
ITF2375806.71± 40.6
ITF2440681.56± 25.8
ITF256399.71± 23.1
Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: %AUCextrap Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1 and on Day 13.

Area under the curve (AUC) is used to describe the total exposure to a drug. The total AUC (AUC0-∞) is the area under the curve from time 0 extrapolated to infinite time. %AUCextrap is the Residual Area or Percentage of Extrapolated Part of AUC0-∞. On Days 1 and 13, givinostat 50 mg as oral suspension was administered as a single dose, in the morning, following an overnight fasting of at least 8 h and subjects remained fasted until at least 4 h post-dose. From Day 5 to Day 12 Givinostat 50 mg as oral suspension was administered twice daily. A total of 48 samples were collected as already des

Single-dose (Day 1)
GroupValue95% CI
Givinostat1.69± 21.7
ITF23745.39± 39.8
ITF23750.93± 97.7
ITF24403.46± 20.9
ITF25633.96± 16.3
Multiple-dose (Day 13)
GroupValue95% CI
Givinostat1.33± 20.6
ITF23742.56± 45.2
ITF23752.13± 220.0
ITF24401.84± 112.1
ITF25631.53± 82.8
Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: λz Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1 and on Day 13.

λz is the Apparent Terminal Elimination Rate Constant. On Day 1 and Day 13, Givinostat 50 mg as oral suspension was administered as a single dose, in the morning, following an overnight fasting of at least 8 hours and subjects remained fasted until at least 4 hours post-dose. From Day 5 to Day 12 Givinostat 50 mg as oral suspension was administered twice daily. A total of 48 blood samples were collected: * 22 during single-dose treatment (Day 1, at pre-dose and at the timepoints indicated in the timeframe post-dose) and * 26 during the multiple dose treatment (Days 5-12 plus single-dose trea

Single-dose (Day 1)
GroupValue95% CI
Givinostat0.097± 15.6
ITF23740.094± 33.0
ITF23750.062± 34.2
ITF24400.060± 15.2
ITF25630.055± 27.8
Multiple-dose (Day 13)
GroupValue95% CI
Givinostat0.067± 24.8
ITF23740.064± 22.5
ITF23750.037± 71.6
ITF24400.047± 49.8
ITF25630.052± 31.5
Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: t1/2 Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1.

t1/2 is the Apparent Terminal Half-Life. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). A total of 22 blood samples were collected as follows: \- 22 blood samples at pre-dose and at the timepoints indicated in the timeframe field after the administration of Givinostat (post-dose), on Days 1, for the determination of Givinostat and its metabolites plasma concentrations. Summary Statistics for the main PK parameters, like t1/2, Following Single-Dose Administration of Givinostat (Day 1) are reported.

GroupValue95% CI
Givinostat7.16± 15.7
ITF23747.40± 32.8
ITF237511.21± 34.4
ITF244011.65± 15.4
ITF256312.57± 27.8
Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: Vd/F Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 1.

Vd/F is the Apparent volume of distribution. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). A total of 22 blood samples were collected as follows: \- 22 blood samples at pre-dose and at the timepoints indicated in the timeframe field after the administration of Givinostat (post-dose), on Days 1, for the determination of Givinostat and its metabolites plasma concentrations. Summary Statistics for the main PK parameters, like Vd/F, Following Single-Dose Administration of Givinostat (Day 1) are reported.

GroupValue95% CI
Givinostat1690.43± 21.7
ITF23740000± 0000
ITF23750000± 0000
ITF24400000± 0000
ITF25630000± 0000
Plasma PK Parameters of Givinostat, Following Multiple-dose Administration of Givinostat: Cmax,ss Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 13.

Cmax,ss is the Maximum Observed Plasma Concentration at steady state. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). A total of 26 blood samples were collected as follows: * 22 blood samples at pre-dose and at the timepoints indicated in the timeframe field after the administration of Givinostat (post-dose), on Day 13, for the determination of Givinostat and its metabolites plasma concentrations. * 4 blood samples before the morning dose of on Days 9, 10, 11 and 12, for the determination of pre-dose plasma concentration of Givinostat and

GroupValue95% CI
Givinostat75.50± 27.0
ITF237420.52± 38.6
ITF2375217.29± 38.1
ITF2440306.60± 15.2
ITF256355.37± 20.3
Plasma PK Parameters of Givinostat, Following Multiple-dose Administration of Givinostat: Tmax,ss Primary · At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 60, 72, 84 and 96 hours post dose on Day 13.

Tmax,ss is the Time of occurrence of Cmax,ss. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported in this platform). A total of 26 blood samples were collected as follows: * 22 blood samples at pre-dose and at the timepoints indicated in the timeframe field after the administration of Givinostat (post-dose), on Day 13, for the determination of Givinostat and its metabolites plasma concentrations. * 4 blood samples before the morning dose of on Days 9, 10, 11 and 12, for the determination of pre-dose plasma concentration of Givinostat and its metabolites. Summar

GroupValue95% CI
Givinostat1.501.50 – 3.00
ITF23745.505.00 – 6.00
ITF23753.502.05 – 4.00
ITF244010.004.00 – 12.00
ITF25639.006.00 – 10.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Throughout the study and 10-14 days after the End of Study (follow-up visit), i.e. up to day 30-34, all TEAEs, considered related or not related to IMPs, were collected.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Total
Serious: 0/8 (0%)
Deaths: 0/8
Other adverse events (14 terms — click to expand)

ReactionSystemTotal
ThrombocytopeniaBlood and lymphatic system disorders
Dry skinSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
Bundle branch block rightCardiac disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
TonsillitisInfections and infestations
Arthropod biteInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Muscle contractureMusculoskeletal and connective tissue disorders
MigraneNervous system disorders
PresyncopeNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Dermatitis contactSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT05860114 adverse events section.

Sponsor's own description

Primary objective: To evaluate the plasma and urine PK of Givinostat following multiple oral doses of Givinostat. Secondary objective: To assess the safety and tolerability multiple oral doses of Givinostat.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing