A Study to Investigate the Effect of Rifampicin on the Uptake and Breakdown of ACT-246475 in Healthy Subjects

Healthy Subject Clinical Trial

Official title:

A Single-center, Randomized, Double-blind, Two-period Cross-over Study to Investigate the Effect of a Single Intravenous Dose of Rifampicin on the Pharmacokinetics of ACT-246475 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03814200
• Other study ID #: ID-076-106
• Secondary ID: 2018-004226-28
• Status: Completed
• Phase: Phase 1
• Start date: January 3, 2019
• Est. completion date: February 19, 2019

Study information

• Verified date: November 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will investigate the effect of rifampicin on the uptake and breakdown of ACT-246475 in healthy subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 19, 2019
• Est. primary completion date: February 12, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Signed informed consent in a language understandable to the subject prior to any study-mandated procedure

• Healthy male and female subjects aged between 18 and 65 years (inclusive) at Screening

• Body mass index of 18.0 to 30.0 kg/m2 (inclusive) at Screening

• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on the same arm, after 5 min in the supine position at screening and on Day -1 of the first period

• Hematology and coagulation test results not deviating from the normal range to a clinically relevant extent at Screening and on Day -1 of the first period

• Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day- 1 of the first treatment period and must agree to consistently and correctly use a highly effective method of contraception

Exclusion Criteria:

• Previous exposure to ACT-246475.

• Previous exposure to rifampicin within 3 months prior to Screening.

• Known hypersensitivity to P2Y12 receptor antagonists or rifampicin, or to any of the rifamycins, or any of their excipients

• Loss of 250 mL or more of blood within 3 months prior to Screening

• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

• Family or personal history of prolonged bleeding (e.g., after surgical intervention) or bleeding disorders (e.g., thrombocytopenia, clotting disturbances), intracranial vascular diseases, stroke, reasonable suspicion of vascular malformations, or peptic ulcers

• Known platelet disorders (e.g., Glanzmann thromboasthenia, von Willebrand disease, platelet release defect)

Related Conditions & MeSH terms

• Healthy Subject

Intervention

Drug:
• Saline
Single i.v. infusion of 100 mL saline 0.9% for 30 min
• ACT-246475
Single s.c. dose of 4 mg ACT-246475 in the thigh under fasting conditions
• Rifampicin
Single i.v. infusion of 600 mg rifampicin (100 mL) for 30 min

Locations

Country	Name	City	State
Netherlands	QPS Netherlands B.V.	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Schilling U, Dingemanse J, Voors-Pette C, Romeijn C, Dogterom P, Ufer M. Effect of Rifampin-Mediated OATP1B1 and OATP1B3 Transporter Inhibition on the Pharmacokinetics of the P2Y12 Receptor Antagonist Selatogrel. Clin Transl Sci. 2020 Sep;13(5):886-890. d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve (AUC) from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t)	The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to 36 hours after treatment administration
Primary	AUC from zero to infinity (AUC0-inf)	The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to 36 hours after treatment administration
Primary	The maximum plasma concentration (Cmax)	The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to 36 hours after treatment administration
Primary	The time to reach Cmax (tmax)	The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to 36 hours after treatment administration
Primary	Terminal half-life (t½)	The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to 36 hours after treatment administration