Clinical trial NCT03814200: A Study to Investigate the Effect of Rifampicin on the Uptake and Breakdown of ACT-246475 in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subject
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2019-01-23
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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


Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: Up to 36 hours after treatment administration
measure: AUC from zero to infinity (AUC0-inf)
timeFrame: Up to 36 hours after treatment administration
measure: The maximum plasma concentration (Cmax)
timeFrame: Up to 36 hours after treatment administration
measure: The time to reach Cmax (tmax)
timeFrame: Up to 36 hours after treatment administration
measure: Terminal half-life (t½)
timeFrame: Up to 36 hours after treatment administration
Secondary outcomes:
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: QPS Netherlands B.V.
Study officials:
References:
citation: 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.