Bioavailability of Belumosudil (KD025) in Healthy Male Subjects
Condition: Bioavailability
Intervention: Belumosudil Tablet; Belumosudil Capsule
Intervention MeSH terms: Belumosudil
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Phase 1 bioavailability study to evaluate the pharmacokinetics (PK) and tolerability/safety
      of the belumosudil tablet formulation in the fasted and fed states and compared to the
      belumosudil capsule formulation in the fed state.
    

Eligibility criteria:

        Inclusion Criteria:

        To be eligible for study entry subjects has to satisfy all of the following criteria:

          1. Healthy males

          2. Aged 18 to 55 years of age

          3. Good state of health (mentally and physically) as indicated by a comprehensive
             clinical assessment (detailed medical history and a complete physical examination),
             ECG, and laboratory investigations (hematology, coagulation, clinical chemistry and
             urinalysis)

          4. Body mass index 18.0-30.0 kg/m^2, or if outside the range, considered not clinically
             significant by the Investigator

          5. Willing and able to communicate and participate in the whole study

          6. Provide written informed consent

          7. Agree to use an adequate method of contraception for up to 90 days post discharge

        Exclusion Criteria

        Subjects are excluded from the study if one of more of the following statements is
        applicable:

          1. Participated in a clinical research study within the previous 3 months

          2. Study site employees, or immediate family members of a study site or sponsor employee

          3. Had been previously enrolled in this study

          4. History of any drug or alcohol abuse in the past 2 years

          5. Regular alcohol consumption > 21 units per week (1 unit = ½ pint beer, 25 mL of 40%
             spirit or a 125 mL glass of wine)

          6. Current smokers and those who had smoked within the last 12 months. A breath carbon
             monoxide (CO) reading of greater than 10 ppm at screening

          7. Did not have suitable veins for multiple venepunctures/cannulation as assessed by the
             Investigator at screening

          8. Clinically significant abnormal biochemistry, hematology, coagulation, or urinalysis
             as judged by the Investigator

          9. Positive drugs of abuse test result or alcohol breath test

         10. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) or
             human immunodeficiency virus (HIV) results

         11. History of any clinically significant cardiovascular, renal, hepatic, chronic
             respiratory or gastrointestinal (GI) disease that may have compromised the subject's
             safety or interfered with the objectives of the study as judged by the investigator

         12. Subject had a history or presence of any of the following:

               -  Active GI disease requiring therapy

               -  Hepatic disease and/or alanine aminotransaminase (ALT) or aspartate
                  aminotransaminase (AST) > 1.5 × upper limit of normal (ULN) at screening

               -  Renal disease and/or serum creatinine > 1.5 × ULN at screening

               -  Other condition known to interfere with the absorption, distribution, metabolism
                  or excretion of drugs

         13. QT interval corrected using Fridericia's formula (QTcF) > 450 msec at the screening or
             admission ECG

         14. Serious adverse reaction or serious hypersensitivity to any drug or the formulation
             excipients

         15. Known sensitivity to ROCK2 inhibitor agents or to any of the constituents of the
             belumosudil formulation

         16. Presence or history of clinically significant allergy requiring treatment, as judged
             by the Investigator. Hayfever is permitted unless it is active.

         17. Donation or loss of > 400 mL of blood within the previous 3 months

         18. Taking or had taken any prescribed or over-the-counter drug (other than 4 g per day
             paracetamol) or herbal remedies in the 14 days before IP administration

         19. Fails to satisfy the Investigator's discretion of fitness to participate or for any
             other reason

        Additional Restrictions

          1. Abstain from alcohol during the 24 h prior to each admission until discharge from the
             clinic in each study period

          2. Not to drink liquids or eat food containing grapefruit, cranberry, caffeine, or other
             xanthines from 24 hours prior to each admission until 48 hours post-dose

          3. Refrain from eating food containing any seeds (e.g., poppy) for 48 hours before the
             screening visit and then from 48 h prior to each admission until discharge from the
             clinic for each study period

          4. Not to take part in any unaccustomed strenuous exercise from 72 hours prior to the
             screening visit and then from 72 hours prior to admission until discharge from the
             study