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

NCT05860114 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ITF/2357/55 - PART 32021-005756-11
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Drug Interaction

Keywords

PK; Pharmacokinetics; Givinostat; Givinostat metabolites

Outcome Measures

Primary Outcomes (20)

• Plasma Pharmacokinetic (PK) Parameters of Givinostat, Following First Single-dose Administration of Givinostat: Cmax

  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) are reported.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: Tmax

  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.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-Dose Administration of Givinostat: Ctrough

  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 Day 13). Of these 26 samples: 22 as per Day 1, and 4 before the morning dose of IMP on Days 9, 10, 11 and 12. PK plasma parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: AUC0-inf.

  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 at Day 13). Of these 26 samples: 22 as per Day 1, and 4 before the morning dose of IMP on Days 9, 10, 11 and 12. PK plasma parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: AUC0-t.

  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 treatment at Day 13). Of these 26 samples: 22 as per Day 1, and 4 before the morning dose of IMP on Days 9, 10, 11 and 12. PK plasma parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: AUC0-τ

  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.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: %AUCextrap

  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 described. PK plasma parameters following single oral dose administration of givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose and Following Multiple-dose Administration of Givinostat: λz

  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 treatment at Day 13). Of these 26 samples: 22 as per Day 1, and 4 before the morning dose of IMP on Days 9, 10, 11 and 12. PK plasma parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: t1/2

  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.

  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.

• Plasma PK Parameters of Givinostat, Following First Single-dose Administration of Givinostat: Vd/F

  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.

  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.

• Plasma PK Parameters of Givinostat, Following Multiple-dose Administration of Givinostat: Cmax,ss

  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 its metabolites. Summary Statistics for Cmax,ss, Following Multiple-Dose of Givinostat (Days 5-12 plus single-dose at Day 13, with values calculated at Day 13) are reported.

  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.

• Plasma PK Parameters of Givinostat, Following Multiple-dose Administration of Givinostat: Tmax,ss

  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. Summary Statistics for Tmax,ss, Following Multiple-Dose of Givinostat (Days 5-12 plus single-dose at Day 13, with values calculated at Day 13) are reported.

  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.

• Plasma PK Parameters of Givinostat, Following Multiple-dose Administration of Givinostat: AUC0-τ,ss

  AUC0-τ,ss is the AUC during a Dosing Interval 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 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. Summary Statistics for AUC0-τ,ss, Following Multiple-Dose of Givinostat (Days 5-12 plus single-dose at Day 13, with values calculated at Day 13) are reported.

  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.

• Plasma PK Parameters of Givinostat, Following Multiple-dose Administration of Givinostat: CLss/F.

  CLss/F is the Apparent total body clearance 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 its metabolites. Summary Statistics for CLss/F, Following Multiple-Dose of Givinostat (Day 13) are reported.

  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.

• Urinary PK Parameters of Givinostat Following First Single-dose and Following Multiple-dose of Givinostat: Rmax.

  Rmax is the Maximum urinary excretion rate. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). Urine was collected, beside on Day -1 (baseline), in the following intervals, on Days 1 and 13, for the determination of the amounts of Givinostat and its metabolites excreted in urine: 0h-12h, 12h-24h, 24h-36h, 36h-48h, 48h-72h and 72h-96h post-dose. Givinostat and its metabolites urine levels were measured using a validated LC-MS/MS analytical method. PK urine parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  0-12, 12-24, 24-36, 36-48, 48-72 and 72-96 hours post-dose on days 1 and 13.

• Urinary PK Parameters of Givinostat Following First Single-dose and Following Multiple-dose of Givinostat: Tumax

  tumax is the Time to Rmax. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). Urine was collected, beside on Day -1 (baseline), in the following intervals, on Days 1 and 13, for the determination of the amounts of Givinostat and its metabolites excreted in urine: 0h-12h, 12h-24h, 24h-36h, 36h-48h, 48h-72h and 72h-96h post-dose. Givinostat and its metabolites urine levels were measured using a validated LC-MS/MS analytical method. PK urine parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  0-12, 12-24, 24-36, 36-48, 48-72 and 72-96 hours post-dose on days 1 and 13.

• Urinary PK Parameters of Givinostat Following First Single-dose and Following Multiple-dose of Givinostat: AmtCUM

  AmtCUM is the Cumulative amount of drug excreted in urine. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). Urine was collected, beside on Day -1 (baseline), in the following intervals, on Days 1 and 13, for the determination of the amounts of Givinostat and its metabolites excreted in urine: 0h-12h, 12h-24h, 24h-36h, 36h-48h, 48h-72h and 72h-96h post-dose. Givinostat and its metabolites urine levels were measured using a validated LC-MS/MS analytical method. PK urine parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  0-12, 12-24, 24-36, 36-48, 48-72 and 72-96 hours post-dose on days 1 and 13.

• Urinary PK Parameters of Givinostat Following First Single-dose and Following Multiple-dose of Givinostat: AURC0-t

  AURC0-t is the Area under the urine excretion curve from time zero to last measurable observed excretion rate. The unit of measure is mg because the value measured is an amount. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). Urine was collected, beside on Day -1 (baseline), in the following intervals, on Days 1 and 13, for the determination of the amounts of Givinostat and its metabolites excreted in urine: 0h-12h, 12h-24h, 24h-36h, 36h-48h, 48h-72h and 72h-96h post-dose. Givinostat and its metabolites urine levels were measured using a validated LC-MS/MS analytical method. PK urine parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  0-12, 12-24, 24-36, 36-48, 48-72 and 72-96 hours post-dose on days 1 and 13.

• Urinary PK Parameters of Givinostat Following First Single-dose and Following Multiple-dose of Givinostat: REC%

  REC% is the Percentage of drug recovered in urine. The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). Urine was collected, beside on Day -1 (baseline), in the following intervals, on Days 1 and 13, for the determination of the amounts of Givinostat and its metabolites excreted in urine: 0h-12h, 12h-24h, 24h-36h, 36h-48h, 48h-72h and 72h-96h post-dose. Givinostat and its metabolites urine levels were measured using a validated LC-MS/MS analytical method. PK urine parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  0-12, 12-24, 24-36, 36-48, 48-72 and 72-96 hours post-dose on days 1 and 13.

• Urinary PK Parameters of Givinostat Following First Single-dose and Following Multiple-dose of Givinostat: CLr/F

  The Givinostat metabolites were: ITF2374, ITF2375, ITF2440, ITF2563 (not reported on this platform). Urine was collected, beside on Day -1 (baseline), in the following intervals, on Days 1 and 13, for the determination of the amounts of Givinostat and its metabolites excreted in urine: 0h-12h, 12h-24h, 24h-36h, 36h-48h, 48h-72h and 72h-96h post-dose. Givinostat and its metabolites urine levels were measured using a validated LC-MS/MS analytical method. PK urine parameters following single oral dose administration of Givinostat (Day 1) and following multiple oral dose administration of Givinostat (Days 5-12 plus single-dose treatment at Day 13, with values on multiple-dose treatment reported at Day 13) were assessed.

  0-12, 12-24, 24-36, 36-48, 48-72 and 72-96 hours post-dose on days 1 and 13.

Secondary Outcomes (1)

• Incidence and Severity of Treatment Emergent Adverse Events

  Throughout the study, until 10-14 days after EoS (Day 17), i.e. till Days 27-31

Study Arms (1)

Givinostat (single-dose and multiple-dose)

EXPERIMENTAL

On Days 1 and 13, Givinostat 50 mg as oral suspension was administered as a single dose, in the morning. On Days 5-12 Givinostat 50 mg as oral suspension was administered twice-daily, in the morning and in the evening, as a multiple dose. PK parameters values following: * single oral dose administration of Givinostat (Day 1) and * multiple oral dose administration of Givinostat (Day 5 to Day 12, with values reported at Day 13) were assessed and reported.

Drug: Givinostat

Interventions

Givinostat DRUG

Drug: ITF2357 Givinostat 10mg/mL Dose: 10mg/mL; Dosage form: oral suspension On days 1 and 13 givinostat was administered in the morning, following an overnight fasting of at least 8 hours and subjects remained fasted until at least 4 hours post-dose. Moreover the subjects were in a semi-recumbent position and remained semi-recumbent until at least 4 hours post-dose.No fluids were allowed from 1 hour before dosing until 2 hours post-dose. Water was provided ad libitum at all other times. From Day 5 to Day 12, subjects received givinostat 50 mg as oral suspension, twice a day, in the morning and in the evening.

Also known as: ITF2357

Givinostat (single-dose and multiple-dose)

Eligibility Criteria

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

You may qualify if:

• Subject's written informed consent obtained prior to any study-related procedure.
• Male or female subject, ≥18 and ≤55 years of age, at the time of signing the informed consent.
• Body mass index (BMI) of 18.5 to 32.0 kg/m2 inclusive, and body weight ≥55 kg and ≤100 kg for females and body weight ≥60 kg and ≤110 kg for males.
• Non-smoker or ex-smoker (i.e. someone who abstained from using tobaccoor nicotine-containing products for at least 3 months prior to Screening).
• No clinically relevant diseases.
• No major surgery within 4 weeks prior to dosing.
• No clinically relevant abnormalities on physical examination.
• No clinically relevant abnormalities on 12-lead ECG.
• No clinically relevant abnormalities on clinical laboratory tests.
• Negative test results for anti-Human Immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAg) and anti-Hepatitis C virus antibodies (anti-HCVAb).
• Female subjects are eligible if they are of non-childbearing potential or agree to use a non-hormonal highly effective contraceptive method from 28 days prior to Screening until at least 90 days after the last study drug administration. Nonchildbearing potential female is defined as:
• Menopausal, i.e. no menses for ≥ 12 months without an alternative medical cause other than menopause, and a high FSH level.
• Pre-menopausal female with documented hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy.
• A non-hormonal effective contraceptive method is defined as:
• Intrauterine device.

You may not qualify if:

• At Screening
• Previous use of givinostat.
• History of anaphylaxis reaction or clinically significant drug hypersensitivity reaction (e.g., angioedema, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, drug-induced hypersensitivity syndrome, druginduced neutropenia).
• Known history of hypersensitivity and/or allergic reactions to givinostat, histone deacetylases (HDAC) inhibitors or to any excipient in the formulation.
• History of sorbitol intolerance, sorbitol malabsorption or fructose intolerance.
• Any medical condition (e.g. gastrointestinal, renal or hepatic, including peptic ulcer, inflammatory bowel disease or pancreatitis) or surgical condition (e.g. cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.
• Systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 60 or over 90 mmHg, or pulse rate lower than 50 or over 100 bpm.
• QTcF ˃450 msec.
• Subjects with history of cardiac arrhythmias (documented), family history of sudden cardiac death or history of additional risk factors for torsades-depointes (e.g. heart failure, hypokalemia, long QT syndrome).
• Having an estimated glomerular filtration (eGFR) \< 90 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average surface area of 1.73 m2.
• Any of the following abnormal laboratory test values:
• Platelet count below the lower limit of the normal range (LLN)
• Total white blood cells count below the LLN
• Hemoglobin below the LLN
• Triglycerides above the upper limit of normal range (ULN)

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (1)

Hospital da Prelada, 3rd Floor & East Wing 4th Floor Rua Sarmento de Beires

Porto, 153, Portugal

Location

MeSH Terms

Interventions

givinostat; givinostat hydrochloride

Results Point of Contact

• Title: Maurizio Caserini, MD
• Organization: Italfarmaco SpA

m.caserini@italfarmacogroup.com

+39 02 64431

Study Officials

• Marlene Fonseca, MD

  Blueclinical, Ltd.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: The study was conducted as open label. Blinding procedures were not applicable.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2023
• First Posted: May 16, 2023
• Study Start: March 21, 2022
• Primary Completion: May 8, 2022
• Study Completion: May 24, 2022
• Last Updated: January 24, 2025
• Results First Posted: January 24, 2025

Record last verified: 2024-07

Locations

PT (1)