Drug-drug Interaction Between Belumosudil, Itraconazole, Rifampicin, Rabeprazole, and Omeprazole in Healthy Volunteers
Condition: Drug-drug Interaction; Autoimmune Diseases; Fibrotic Disease
MeSH terms: Autoimmune Diseases
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Belumosudil; Itraconazole; Rabeprazole; Rifampicin; Omeprazole
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Development candidate; Perpetrator drug; Perpetrator drug; Perpetrator drug; Perpetrator drug
Other intervention name(s): Rezurock; SLx-2119
Intervention MeSH terms: Itraconazole; Rifampin; Omeprazole; Rabeprazole; Belumosudil
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Two-Part, Non-Randomised
Masking: None (Open Label)
Primary purpose: Basic Science