NCT03530995

Drug-drug Interaction Between Belumosudil, Itraconazole, Rifampicin, Rabeprazole, and Omeprazole in Healthy Volunteers

A 2-Part, Non-randomized, Open-label Study to Evaluate the Effect of Itraconazole, Rifampicin, Rabeprazole, and Omeprazole on the Pharmacokinetics of Belumosudil (KD025)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 73 (actual)
• Sponsor: Kadmon Corporation, LLC · Industry
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This is a single-center, 2-part, non-randomized, open-label study of the drug-drug interactions of belumosudil (KD025) with itraconazole, rifampicin, rabeprazole, and omeprazole in healthy male subjects.

Detailed description

Part 1: The primary objective of Part 1 of this study is to determine the effect of itraconazole, rifampicin, and rabeprazole on the pharmacokinetics of once daily (QD) orally administered belumosudil in healthy male subjects. Part 1 consists of 4 periods. In each study period, subjects will receive a single dose of belumosudil, in the fed state. Additionally, in order to assess the effects of inhibition and induction of CYP3A4 and the elevation of gastric pH on belumosudil exposure, subjects will receive multiple doses of perpetrator drugs in Periods 2 to 4; a strong CYP3A4 inhibitor, itraconazole, in Period 2; a proton pump inhibitor, rabeprazole, in Period 3; and a strong CYP3A4 inducer, rifampicin, in Period 4. Subjects will receive a total of 4 single oral dosses of investigative product (IP), 200 mg belumosudil QD, in the fed state over 4 periods (each lasting 3 days with a minimum washout of 2, 8, and 4 days following completion of Periods 1, 2, and 3, respectively). Subjects also will receive 9 single oral doses of itraconazole 200 mg (QD over 9 days) in Period 2; 7 single oral doses of rabeprazole 20 mg (BID over 3 days followed by QD on 1 day) in Period 3; and 9 single doses of rifampicin 600 mg (QD over 9 days) in Period 4. A follow-up visit will take place 3 to 5 days post-final discharge. Part 2: The primary objective of Part 2 of this study is to determine the effect of omeprazole on the PK of a single-day twice daily (BID; every 12 hours \[Q12h\]) dose of belumosudil administered orally, in healthy male subjects. Part 2 consists of 2 periods. In Period 1, subjects will receive a single dose of belumosudil, in the fed state. In Period 2, in order to assess the effects of inhibition and induction of CYP3A4 and the elevation of gastric pH on belumosudil exposure, subjects will receive multiple doses of a proton pump inhibitor, omeprazole. Subjects will receive a total of 4 single oral doses of IP (200 mg belumosudil, BID \[Q12h\] on 2 occasions) in the fed state over 2 periods (each lasting 3 days with a minimum washout of 2 days between dosing in Period 1 and the start of dosing with non-IP in Period 2). Subjects will also receive 4 single oral doses of omeprazole 20 mg (QD over 4 days) in Period 2. A follow-up visit will take place 3 to 5 days post-final discharge.

Conditions

• Drug-drug Interaction
• Autoimmune Diseases
• Fibrotic Disease

Interventions

Type	Name	Description
DRUG	Belumosudil	Development candidate
DRUG	Itraconazole	Perpetrator drug
DRUG	Rabeprazole	Perpetrator drug
DRUG	Rifampicin	Perpetrator drug
DRUG	Omeprazole	Perpetrator drug

Timeline

• Start date: 2018-04-09
• Primary completion: 2019-02-08
• Completion: 2019-02-08
• First posted: 2018-05-21
• Last updated: 2022-05-25
• Results posted: 2021-09-13

Locations

1 site across 1 country: United Kingdom