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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05492318
Other study ID # ITF/2357/55
Secondary ID 2021-005756-11
Status Completed
Phase Phase 1
First received
Last updated
Start date March 21, 2022
Est. completion date May 24, 2022

Study information

Verified date August 2022
Source Italfarmaco
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The study will evaluate the givinostat (ITF2357) potential drug-drug interaction (DDI) at level of CYP3A-mediated metabolism and P-glycoprotein (P-gp) transport.


Recruitment information / eligibility

Status Completed
Enrollment 54
Est. completion date May 24, 2022
Est. primary completion date May 8, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria: - 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 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 tobacco- or nicotine-containing products for at least 3 months prior to Screening). - No clinically relevant diseases and no major surgery. - No clinically relevant abnormalities on physical examination, on 12-lead ECG, on clinical laboratory tests. - Negative Virology test results - Female subjects a of non-childbearing potential or agree to use a non-hormonal highly effective contraceptive. - Male subjects must ensure d a highly effective method of contraception - Willingness and capability to comply with the requirements of the study and ability to understand the study procedures and the risks involved. Exclusion Criteria: - Previous use of givinostat. - History of anaphylaxis reaction or clinically significant drug hypersensitivity reaction and/or allergic reactions to givinostat, histone deacetylases (HDAC) inhibitors or to any excipient in the formulation, midazolam, other benzodiazepines, dabigatran etexilate or to any excipient of the formulation, clarithromycin, other macrolides or to any excipient in the formulation. - History of sorbitol intolerance, sorbitol malabsorption or fructose intolerance. - Any medical condition that may affect drug pharmacokinetics or subject safety. - Normal blood pressure - Subjects with history of cardiac arrhythmias/abnormalities - Having an estimated glomerular filtration (eGFR) < 90 mL/min - Platelet count, Total white blood cells count, Hemoglobin, Potassium or magnesium below the lower limit of the normal range (LLN) - Triglycerides above the upper limit of normal range (ULN) - Positive urine alcohol, drugs-of-abuse or cotinine screen tests. - Positive serum or urine pregnancy test. - If woman, she is breast-feeding - History of alcohol or drug abuse - Any clinically relevant abnormalities on clinical laboratory tests. - Use of prescription or non-prescription medicinal products - Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study. - Clinically relevant history of impaired respiratory function, obstructive sleep apnea, myasthenia gravis, respiratory arrest and/or cardiac arrest. - History of glaucoma. - Presence of active clinically significant bleeding, lesion or condition considered to pose a significant risk factor for major bleeding, presence of a medical condition requiring anticoagulant treatment.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
ITF2357 Givinostat 10mg/mL
Dose: 10 mg/mL; Dosage form: oral suspension
Midazolam 1Mg/Ml (Pf) Inj Syringe 5Ml
Dose: 1 mg/ml; Dosage form: solution for injection/infusion or rectal administration
Midazolam Oral Liquid Product
Dose: 2.5 mg; Dosage form: oromucosal solution
Dabigatran Etexilate 75 MG [Pradaxa]
Dose: 75 mg; Dosage form: hard capsules
Clarithromycin 500Mg Tab
Dose: 500 mg; Dosage form: immediate-release film-coated tablets

Locations

Country Name City State
Portugal Hospital da Prelada, 3rd Floor & East Wing 4th Floor Rua Sarmento de Beires Porto

Sponsors (1)

Lead Sponsor Collaborator
Italfarmaco

Country where clinical trial is conducted

Portugal, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum observed plasma concentration (Cmax) for midazolam, 1-hydroxymidazolam, total dabigatran, free dabigatran, givinostat (Part 2 and 3) and its metabolites (Part 3), following single doses of the parent drug PK samples will be collected:
- at baseline condition (Midazolam (IV and oral) 24 hours PK plasma profile; dabigatran etexilate 72 hours PK plasma profile),
Midazolam IV 24h PK plasma profile & dabigatran etexilate 72 hours PK plasma profile: at day 1,6,17. Midazolam oral 24h PK plasma profile: at day 2,7,18
Primary Maximum observed plasma concentration (Cmax) for midazolam, 1-hydroxymidazolam, total dabigatran, free dabigatran, givinostat (Part 2 and 3) and its metabolites (Part 3), following single doses of the parent drug PK samples will be collected:
- after a co-administration with Givinostat before the Steady state (Midazolam (IV and oral) 24 hours PK plasma profile; dabigatran etexilate 72 hours PK plasma profile)
Midazolam IV 24h PK plasma profile & dabigatran etexilate 72 hours PK plasma profile: at day 1,6,17. Midazolam oral 24h PK plasma profile: at day 2,7,18
Primary Maximum observed plasma concentration (Cmax) for midazolam, 1-hydroxymidazolam, total dabigatran, free dabigatran, givinostat (Part 2 and 3) and its metabolites (Part 3), following single doses of the parent drug PK samples will be collected:
- after co-administration with Givinostat at Steady state (Midazolam (IV and oral) 24 hours PK plasma profile; dabigatran etexilate 72 hours PK plasma profile
Midazolam IV 24h PK plasma profile & dabigatran etexilate 72 hours PK plasma profile: at day 1,6,17. Midazolam oral 24h PK plasma profile: at day 2,7,18
Primary Time of occurrence of Cmax (tmax) for midazolam, 1-hydroxymidazolam, total dabigatran, free dabigatran, givinostat (Part 2 and 3) and its metabolites (Part 3), following single doses of the parent drug Midazolam IV 24h PK plasma profile & dabigatran etexilate 72 hours PK plasma profile: at day 1,6,17. Midazolam oral 24h PK plasma profile: at day 2,7,18
Primary AUC from pre-dose (time zero) to the last sampling time with quantifiable concentrations (AUC0-t) or midazolam, 1-hydroxymidazolam, total dabe, free dabe, givinostat (Part 2&3) and its metabolites (Part 3), following single doses of Givi Midazolam IV 24h PK plasma profile & dabigatran etexilate 72 hours PK plasma profile: at day 1,6,17. Midazolam oral 24h PK plasma profile: at day 2,7,18
Primary Maximum observed plasma concentration at steady state (Cmax,ss) for givinostat and its metabolites using the individual plasma concentration-time profiles Day 13 part 3
Primary Time of occurrence of Cmax,ss (tmax,ss) for givinostat and its metabolites using the individual plasma concentration-time profiles Day 13 part 3
Primary AUC during the dosing interval, at steady-state (AUC0-t,ss) for givinostat and its metabolites using the individual plasma concentration-time profiles Day 13 part 3
Primary Maximum urinary excretion rate (Rmax) after the first dose and the last dose of Givinostat Day 1 and day 13: Part 3
Primary Time to Rmax (tumax) after the first dose and the last dose of Givinostat at pre-dose and up to 96 hours on Day 1 and day 13: Part 3
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