Perpetrator DDI Potential of Givinostat as Inhibitor and Inducer of CYP3A and P-gp Activity

• Status: Completed
• Trial end date: 2022-05-24
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Italfarmaco
• Treatments: Clarithromycin; Dabigatran; Givinostat hydrochloride; Midazolam

Criteria

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.