Ignite Creation Date:
2025-12-25 @ 4:33 AM
Ignite Modification Date:
2025-12-26 @ 3:35 AM
Study NCT ID:
NCT05492318
Status:
COMPLETED
Last Update Posted:
2025-01-06
First Post:
2022-06-09
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Perpetrator DDI Potential of Givinostat as Inhibitor and Inducer of CYP3A and P-gp Activity
Sponsor:
Italfarmaco
Organization:
Study Overview
Official Title:
Open-label, Single-center Study in Healthy Subjects to Investigate the Effect of Oral Givinostat on Pharmacokinetics (PK) of Intravenous and Oral Midazolam and Oral Dabigatran Etexilate (PART 1)
Status:
COMPLETED
Status Verified Date:
2024-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Detailed Description:
This study was planned as a phase I, open-label, 3-part, fixed-sequence, nonrandomized study in healthy male and female subjects. The study evaluated the givinostat (ITF2357) potential drug-drug interaction (DDI) at level of CYP3A-mediated metabolism and P-glycoprotein (P-gp) transport with intravenous or oral midazolam and with oral dabigatran etexilate.
More precisely, the study aimed at assessing the potential (inhibitory or inducing) effect of givinostat on the PK of midazolam IV, on the PK of oral midazolam and on the PK of dabigatran etexilate.
The study lasted from Day 1 to Day 20. Subjects were confined from Day -1 to Day 20. On Days 6 and 17, single doses of 1 mg midazolam IV and 75 mg dabigatran etexilate, were administered 1 hour after the planned morning time of givinostat administration. On day 1, however, drugs were not administered 1h after gininostat.
On Days 7 and 18, a single oral dose of 2.5 mg midazolam oral solution was administered 1 hour after the planned morning time of givinostat administration.
On day 2, however, the drugs were not administered 1h after gininostat.
From Day 4 to Day 18, givinostat 50 mg as oral suspension was administered twice a day, in the morning and in the evening.
On Day 19, only the morning dose was administered.
The following assessments were performed:
* Blood collection for pharmacokinetic analysis on Days 1 to 4, 6 to 9 and 17 to 20.
* Vital signs measurements (BP, PR and RR) on Days 1, 2, and 4 to 19.
* 12-lead ECG on Days 3 to 19.
* Blood collection for laboratory tests (hematology, biochemistry and coagulation on Days 4 and 9 and hematology on Days 6, 12, 15 and 18). Subjects were discharged from BlueClinical Phase I in the morning of Day 20 if allowed by the investigator based on their medical condition. The following procedures were performed:
* Physical examination.
* Collection of body weight.
* Vital signs measurements (BP, PR, RR and body temperature).
* 12-lead ECG.
* Safety laboratory assessments (hematology, biochemistry, coagulation and urinalysis).
* Serum pregnancy test for all female subjects. Subjects returned to the site 10 to 14 days after the end of study to undergo additional assessments as required per protocol.
The total duration of Part 1 for each subject was up to approximately 8 weeks from Screening to Follow-up visit, divided as follows:
* Screening: up to 21 days
* Treatment Period: Days 1 to 20
* Safety follow-up visit: 12±2 days
More precisely, the study aimed at assessing the potential (inhibitory or inducing) effect of givinostat on the PK of midazolam IV, on the PK of oral midazolam and on the PK of dabigatran etexilate.
The study lasted from Day 1 to Day 20. Subjects were confined from Day -1 to Day 20. On Days 6 and 17, single doses of 1 mg midazolam IV and 75 mg dabigatran etexilate, were administered 1 hour after the planned morning time of givinostat administration. On day 1, however, drugs were not administered 1h after gininostat.
On Days 7 and 18, a single oral dose of 2.5 mg midazolam oral solution was administered 1 hour after the planned morning time of givinostat administration.
On day 2, however, the drugs were not administered 1h after gininostat.
From Day 4 to Day 18, givinostat 50 mg as oral suspension was administered twice a day, in the morning and in the evening.
On Day 19, only the morning dose was administered.
The following assessments were performed:
* Blood collection for pharmacokinetic analysis on Days 1 to 4, 6 to 9 and 17 to 20.
* Vital signs measurements (BP, PR and RR) on Days 1, 2, and 4 to 19.
* 12-lead ECG on Days 3 to 19.
* Blood collection for laboratory tests (hematology, biochemistry and coagulation on Days 4 and 9 and hematology on Days 6, 12, 15 and 18). Subjects were discharged from BlueClinical Phase I in the morning of Day 20 if allowed by the investigator based on their medical condition. The following procedures were performed:
* Physical examination.
* Collection of body weight.
* Vital signs measurements (BP, PR, RR and body temperature).
* 12-lead ECG.
* Safety laboratory assessments (hematology, biochemistry, coagulation and urinalysis).
* Serum pregnancy test for all female subjects. Subjects returned to the site 10 to 14 days after the end of study to undergo additional assessments as required per protocol.
The total duration of Part 1 for each subject was up to approximately 8 weeks from Screening to Follow-up visit, divided as follows:
* Screening: up to 21 days
* Treatment Period: Days 1 to 20
* Safety follow-up visit: 12±2 days
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2021-005756-11 | EUDRACT_NUMBER | None | View |