CompletedPhase 1

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

Portugal26 participantsStarted 2022-03-21

Plain-language summary

Primary objective: 1. To assess the potential inhibitory and inducing effect of oral givinostat on the single dose pharmacokinetics (PK) of intravenous or oral midazolam. 2. To assess the potential inhibitory and inducing effect of oral givinostat on the single dose PK of oral dabigatran etexilate. Secondary objective: To assess the safety and tolerability of concomitant administration of givinostat plus midazolam and dabigatran etexilate.

Who can participate

Age range18 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 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.

Exclusion criteria

✕. 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.
✕

What they're measuring

Cmax for Midazolam, 1-hydroxymidazolam, Following Single Doses of the Parent Drug

Timeframe: In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.

Cmax for Dabigatran (Total and Free), Following Single Doses of the Parent Drug

Timeframe: In the turn of 72 hours after administration of dabigatran on day 1,6,17

Tmax for Midazolam, 1-hydroxymidazolam, Following Single Doses of the Parent Drug

Timeframe: In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.

Tmax for Dabigatran (Total and Free), Following Single Doses of the Parent Drug

Timeframe: In the turn of 72 hours after administration of dabigatran on day 1,6,17

t1/2 of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat

Timeframe: In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.

t1/2 for Dabigatran (Total and Free), Following Single Doses of the Parent Drug

Timeframe: In the turn of 72 hours after administration of dabigatran on day 1,6,17

Trial details

NCT IDNCT05492318

SponsorItalfarmaco

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2022-05-08

Results submitted2023-04-26

View on ClinicalTrials.gov More Drug-Drug Interaction trials

Plain-language summary

Who can participate

Age range18 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 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.

Exclusion criteria

✕. 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.
✕