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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subject
• Intervention / Treatment: Drug: Saline; Drug: ACT-246475; Drug: Rifampicin

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700
    • QPS Netherlands B.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment period A; Treatment A1: saline 0.9% followed by Treatment A2: ACT-246475	Drug: Saline; Single i.v. infusion of 100 mL saline 0.9% for 30 min; Drug: ACT-246475; Single s.c. dose of 4 mg ACT-246475 in the thigh under fasting conditions; Other Names: Selatogrel
Experimental: Treatment period B; Treatment B1: rifampicin followed by Treatment B2: ACT-246475	Drug: ACT-246475; Single s.c. dose of 4 mg ACT-246475 in the thigh under fasting conditions; Other Names: Selatogrel; Drug: Rifampicin; Single i.v. infusion of 600 mg rifampicin (100 mL) for 30 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Viatris Innovation GmbH
• Investigators: Study Director: Clinical Trials, Viatris Innovation GmbH

Publications and helpful links

General Publications

• 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. doi: 10.1111/cts.12774. Epub 2020 Mar 31.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Actual): February 12, 2019
• Study Completion (Actual): February 19, 2019

Study Registration Dates

• First Submitted: January 21, 2019
• First Submitted That Met QC Criteria: January 21, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; Rifampin
• Other Study ID Numbers: ID-076-106; 2018-004226-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No