Drug-Drug Interaction Clinical Trial
Official title:
An Open-label, Single-center, Three-part Study in Healthy Subjects to Investigate the Effect of Givinostat on the Pharmacokinetics of Midazolam and Dabigatran, the Effect of Clarithromycin on the Pharmacokinetics of Givinostat and the Pharmacokinetics of Single and Multiple Doses of Givinostat
Verified date | August 2022 |
Source | Italfarmaco |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The study will evaluate the givinostat (ITF2357) potential drug-drug interaction (DDI) at level of CYP3A-mediated metabolism and P-glycoprotein (P-gp) transport.
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. |
Country | Name | City | State |
---|---|---|---|
Portugal | Hospital da Prelada, 3rd Floor & East Wing 4th Floor Rua Sarmento de Beires | Porto |
Lead Sponsor | Collaborator |
---|---|
Italfarmaco |
Portugal,
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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05692570 -
A Study of PBI-200 With Ritonavir or Cobicistat in Healthy Volunteers
|
Phase 1 | |
Completed |
NCT04328766 -
Pharmacokinetic Interaction Between DWP14012 and DWC202005 in Healthy Volunteers
|
Phase 1 | |
Completed |
NCT03990129 -
Pharmacokinetic Interactions of Metamizole (Dipyrone) in Healthy Subjects
|
Phase 1 | |
Completed |
NCT03985969 -
Study to Investigate the Potential Drug-Drug Interaction Between Elafibranor and Indomethacin
|
Phase 1 | |
Completed |
NCT03302845 -
A Phase 1 Study to Evaluate the Effects of Omeprazole and Famotidine on the Absorption of Telotristat Ethyl in Healthy Subjects
|
Phase 1 | |
Completed |
NCT02887443 -
A Study to Assess the Potential for Pre-systemic Inhibition of CYP3A by Idebenone Using Midazolam as a Substrate
|
Phase 1 | |
Completed |
NCT01361217 -
The Effects of Multiple Dose Fluoxetine and Metabolites on CYP1A2, CYP2C19, CYP2D6 and CYP3A4 Activity
|
N/A | |
Completed |
NCT06066060 -
A DDI Study of JMKX000623 and Metformin Hydrochloride
|
Phase 1 | |
Completed |
NCT03723395 -
A Drug-Drug Interaction Study in Healthy Volunteers of the Effects of Tucatinib
|
Phase 1 | |
Recruiting |
NCT05789173 -
Interaction of CYP2B6 Genotype and Efavirenz With Methadone and Tizanidine PK
|
Early Phase 1 | |
Completed |
NCT04598542 -
Drug-Drug Interaction Study of Lorecivivint and Triamcinolone Acetonide in Healthy Volunteers
|
Phase 1 | |
Recruiting |
NCT05044962 -
Kuwa Free! - Live Free!
|
N/A | |
Completed |
NCT04487145 -
Dihydroartemisinin-Piperaquine in the Context of Antiretroviral Therapy
|
Phase 4 | |
Completed |
NCT05108051 -
Study to Investigate the Potential Drug-Drug Interaction Between ZSP1273 and Oseltamivir
|
Phase 1 | |
Active, not recruiting |
NCT04669678 -
Evaluation of Pharmacokinetic Drug-drug Interactions Between Hormonal Contraceptives and Doravirine-containing ART Among Women Living With HIV in South Africa
|
Phase 4 | |
Completed |
NCT01991327 -
Assessment of Drug-Drug Interactions of Androxal With Cytochrome P450 Isoenyzmes in Healthy Males
|
Phase 1 | |
Completed |
NCT04218513 -
Drug-drug Interaction Study Between Edaravone and 2-Aminoethanesulfonic Acid in Compound Edaravone Injection
|
Phase 1 | |
Completed |
NCT01309854 -
Effects of Administration of Fostamatinib on Blood Concentrations of Pioglitazone in Healthy Subjects
|
Phase 1 | |
Recruiting |
NCT05339672 -
Determining the Clinical Relevance of the Interaction Between Enzalutamide and the Opioid Morphine and the DOAC Edoxaban
|
||
Completed |
NCT05306379 -
Drug-Drug Interaction Study to Investigate Effects of Voclosporin on Pharmacokinetics of Simvastatin
|
Phase 1 |